CN111356700A - 受约束的条件性活化的结合蛋白 - Google Patents

受约束的条件性活化的结合蛋白 Download PDF

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CN111356700A
CN111356700A CN201880072182.XA CN201880072182A CN111356700A CN 111356700 A CN111356700 A CN 111356700A CN 201880072182 A CN201880072182 A CN 201880072182A CN 111356700 A CN111356700 A CN 111356700A
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C·梅
R·B·杜布里奇
M·维诺格拉多沃娃
A·潘沙尔
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Takeda Pharmaceutical Co Ltd
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Abstract

本发明涉及以活性前药形式施用的条件性双特异性重定向的活化构建体或COBRA。在暴露于肿瘤蛋白酶后，所述构建体被裂解并被活化，这样它们能够结合肿瘤靶抗原(TTA)以及CD3两者，由此将表达CD3的T细胞募集至肿瘤，从而进行治疗。

Description

受约束的条件性活化的结合蛋白
I.相关申请的交叉引用
本申请根据美国法典第35篇119条(e)款要求2017年9月8日提交的美国临时专利申请62/555,943、2017年11月15日提交的美国临时专利申请62/586,627和2017年11月16日提交的美国临时专利申请62/587,318的优先权，所述临时专利申请全部明确地以引用的方式整体并入本文。
II.对在压缩光盘上提交的“序列表”、表格或计算机程序列表附件的引用。
名称为“118459-5005_ST25.txt”、大小为984千字节的文件中包含的序列表已经由EFS-Web与本文一起以电子方式提交，并且所述txt文件的内容特此以引用的方式整体并入。
III.发明背景
在各种临床环境中，通常需要选择性破坏单独细胞或特定细胞类型。例如，癌症疗法的主要目标是特异性地破坏肿瘤细胞，同时使健康的细胞和组织尽可能完整无损。一种这样的方法是通过诱导针对肿瘤的免疫应答以使诸如自然杀伤(NK)细胞或细胞毒性T淋巴细胞(CTL)的免疫效应细胞攻击并破坏肿瘤细胞来进行。
完整单克隆抗体(mAb)(其为肿瘤相关抗原提供优异的结合特异性和亲和力)的使用已成功应用于癌症治疗和诊断领域。但是，完整mAb的大尺寸、它们的较差生物分布、低效力以及在血池中持久存在限制了它们的临床应用。例如，完整抗体可在肿瘤区域内表现出特异性累积。在生物分布研究中，当精确检查肿瘤时，注意到抗体分布不均匀，主要累积在外周区域中。由于肿瘤坏死、不均匀的抗原分布和增加的间质组织压力，不可能以完整抗体构建体到达肿瘤的中心部分。相比之下，较小的抗体片段显示出快速的肿瘤定位，更深地渗透到肿瘤中并且也相对快速地从血流中清除。然而，许多抗体(包括scFv和其他构建体)显示出“中靶/脱肿瘤(on target/off tumor)”效应，其中分子在非肿瘤细胞上具有活性，从而引起副作用，所述副作用中的一些可能是毒性副作用。本发明涉及在肿瘤蛋白酶存在下选择性地活化的新型构建体。
IV.发明内容
本发明提供了许多用于治疗癌症的不同蛋白质组合物。因此，在一方面，本发明提供了“形式2”蛋白质，所述形式2蛋白质从N-末端至C-末端包含：结合至人肿瘤靶抗原(TTA)的第一单结构域抗原结合结构域(sdABD)(sdABD-TTA)；b)第一结构域接头；c)受约束的Fv结构域，所述受约束的Fv结构域包含：i)包含vhCDR1、vhCDR2和vhCDR3的第一可变重结构域；ii)受约束的不可裂解的接头(CNCL)；和iii)包含vlCDR1、vlCDR2和vlCDR3的第一可变轻结构域；d)第二结构域接头；e)第二sdABD-TTA；f)可裂解的接头(CL)；g)受约束的伪Fv结构域，所述受约束的伪Fv结构域包含：i)第一伪轻可变结构域；ii)不可裂解的接头(NCL)；和iii)第一伪重可变结构域；h)第三结构域接头；以及i)结合至人血清白蛋白的第三sdABD；其中所述第一可变重结构域和所述第一可变轻结构域能够结合人CD3，但所述受约束的Fv结构域不结合CD3；所述第一可变重结构域和所述第一伪可变轻结构域分子内缔合以形成无活性的Fv；并且所述第一可变轻结构域和所述第一伪可变重结构域分子内缔合以形成无活性的Fv。
在进一步的方面，本发明提供了“形式1”蛋白质，所述形式1蛋白质从N-末端至C-末端包含：a)第一sdABD-TTA；b)第一结构域接头；c)受约束的Fv结构域，所述受约束的Fv结构域包含：i)包含vhCDR1、vhCDR2和vhCDR3的第一可变重结构域；ii)受约束的可裂解的接头(CCL)；和iii)包含vlCDR1、vlCDR2和vlCDR3的第一可变轻结构域；d)第二结构域接头；e)第二sdABD-TTA；f)可裂解的接头(CL)；g)受约束的伪Fv结构域，所述受约束的伪Fv结构域包含：i)第一伪轻可变结构域；ii)不可裂解的接头(NCL)；和iii)第一伪重可变结构域；h)第三结构域接头；以及i)结合至人血清白蛋白的第三sdABD；其中所述第一可变重结构域和所述第一可变轻结构域能够结合人CD3，但所述受约束的Fv结构域不结合CD3；其中所述第一可变重结构域和所述第一伪可变轻结构域分子内缔合以形成无活性的Fv；并且其中所述第一可变轻结构域和所述第一伪可变重结构域分子内缔合以形成无活性的Fv。
在另外的方面，本发明提供了“形式4”蛋白质，所述“形式4”蛋白质从N-末端至C-末端包含：a)结合至人肿瘤靶抗原(TTA)的单结构域抗原结合结构域(sdABD)(sdABD-TTA)；b)第一结构域接头；c)受约束的Fv结构域，所述受约束的Fv结构域包含：i)包含vhCDR1、vhCDR2和vhCDR3的第一可变重结构域；ii)受约束的不可裂解的接头(CNCL)；和iii)包含vlCDR1、vlCDR2和vlCDR3的第一可变轻结构域；d)可裂解的接头(CL)；e)结合至人血清白蛋白的第二sdABD；f)结构域接头；g)受约束的伪Fv结构域，所述受约束的伪Fv结构域包含：i)第一伪轻可变结构域；ii)不可裂解的接头(NCL)；和iii)第一伪重可变结构域；其中所述第一可变重结构域和所述第一可变轻结构域能够结合人CD3，但所述受约束的Fv结构域不结合CD3；其中所述第一可变重结构域和所述第一伪可变轻结构域分子内缔合以形成无活性的Fv；并且其中所述第一可变轻结构域和所述第一伪可变重结构域分子内缔合以形成无活性的Fv。
在上文列出的形式1、形式2和形式4蛋白质的进一步方面，所述第一可变重结构域在所述第一可变轻结构域的N-末端，并且所述伪轻可变结构域在所述伪可变重结构域的N-末端。
在上文列出的形式1、形式2和形式4蛋白质的进一步方面，所述第一可变重结构域在所述第一可变轻结构域的N-末端，并且所述伪可变重结构域在所述伪可变轻结构域的N-末端。
在上文列出的形式1、形式2和形式4蛋白质的进一步方面，所述第一可变轻结构域在所述第一可变重结构域的N-末端，并且所述伪轻可变结构域在所述伪可变重结构域的N-末端。
在上文列出的形式1、形式2和形式4蛋白质的进一步方面，所述第一可变轻结构域在所述第一可变重结构域的N-末端，并且所述伪可变重结构域在所述伪可变轻结构域的N-末端。
在另外的方面，本发明提供了形式1和形式2蛋白质，其中所述第一和第二TTA是相同的。
在进一步的方面，本发明提供了形式1和形式2蛋白质，其中所述第一和第二TTA是不同的。
在另外的方面，本发明提供了形式1、形式2和形式4蛋白质，其中所述第一和第二TTA选自EGFR、EpCAM、FOLR1和B7H3。这些序列可选自由以下组成的组：SEQ ID NO:1、SEQ IDNO:5、SEQ ID NO:9、SEQ ID NO:13、SEQ ID NO:17、SEQ ID NO:21、SEQ ID NO:25、SEQ IDNO:29、SEQ ID NO:33、SEQ ID NO:37以及SEQ ID NO:41。
在进一步的方面，本发明提供了形式1、形式2和形式4蛋白质，其中所述半衰期延长结构域具有SEQ ID NO:45。
在另外的方面，本发明提供了形式1、形式2和形式4蛋白质，其中所述可切割的接头被选自由以下组成的组的人蛋白酶切割：MMP2、MMP9、穿膜肽酶A、穿膜肽酶B、组织蛋白酶S、组织蛋白酶K、组织蛋白酶L、颗粒酶B、uPA、激肽释放酶7、蛋白裂解酶和凝血酶。
在进一步的方面，本发明提供了一种蛋白质，所述蛋白质选自由以下组成的组：Pro186、Pro225、Pro226、Pro233、Pro311、Pro312、Pro313、Pro495、Pro246、Pro254、Pro255、Pro256、Pro420、Pro421、Pro432、Pro479、Pro480、Pro187、Pro221、Pro222、Pro223、Pro224、Pro393、Pro394、Pro395、Pro396、Pro429、Pro430以及Pro431。
在另外的方面，本发明提供了编码如本文所述的形式1、形式2或形式4蛋白质的核酸，以及包含编码所述蛋白质的核酸的表达载体和宿主细胞。
在进一步的方面，本发明提供了制备本发明的蛋白质的方法和治疗有需要的患者的方法。
在另外的方面，本发明提供了包含“形式3A”前药蛋白质对的组合物，所述“形式3A”前药蛋白质对包含：a)第一蛋白质，所述第一蛋白质从N-末端至C-末端包含：i)第一sdABD-TTA；ii)第一结构域接头；iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：1)包含vhCDR1、vhCDR2和vhCDR3的可变重链；2)可切割的接头；和3)包含iVLCDR1、iVLCDR2和iVLCDR3的第一伪可变轻结构域；iv)第二结构域接头；v)sdABD-HSA；a)第二蛋白质，所述第二蛋白质从N-末端至C-末端包含：i)结合至人肿瘤靶抗原的第三sdABD；ii)第三结构域接头；iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：1)包含VLCDR1、VLCDR2和VLCDR3的可变轻链；2)可裂解的接头；3)包含iVHCDR1、iVHCDR2和iVHCDR3的第一伪可变重结构域；iv)第四结构域接头；v)sdABD-HSA；其中所述第一可变重结构域和所述第一可变轻结构域能够在缔合时结合人CD3；其中所述第一可变重结构域和所述第一伪可变轻结构域分子间缔合以形成无活性的Fv；其中所述第一可变轻结构域和所述第一伪可变重结构域分子间缔合以形成无活性的Fv；并且其中所述第一和第三sdABD选自由以下组成的组：SEQ ID NO:1、SEQ ID NO:5、SEQ ID NO:9、SEQ ID NO:13、SEQ ID NO:17、SEQ ID NO:21、SEQ ID NO:25、SEQ ID NO:29、SEQ ID NO:33、SEQ ID NO:37以及SEQ ID NO:41。
在进一步的方面，本发明提供了包含“形式3B”前药蛋白质对的组合物，所述“形式3B”前药蛋白质对包含：a)第一蛋白质，所述第一蛋白质从N-末端至C-末端包含：i)第一sdABD-TTA；ii)第一结构域接头；iii)第二sdABD-TTA；iv)第二结构域接头；iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：1)包含vhCDR1、vhCDR2和vhCDR3的可变重链；2)可裂解的接头；和3)包含iVLCDR1、iVLCDR2和iVLCDR3的第一伪可变轻结构域；iv)第三结构域接头；和v)sdABD-HSA；a)第二蛋白质，所述第二蛋白质从N-末端至C-末端包含：i)第三sdABD-TTA；ii)第四结构域接头；iii)第四sdABD-TTA；iv)第五结构域接头；iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：1)包含VLCDR1、VLCDR2和VLCDR3的可变轻链；2)可裂解的接头；和3)包含iVHCDR1、iVHCDR2和iVHCDR3的第一伪可变重结构域；iv)第六结构域接头；v)sdABD-HSA；其中所述第一可变重结构域和所述第一可变轻结构域能够在缔合时结合人CD3；其中所述第一可变重结构域和所述第一伪可变轻结构域分子间缔合以形成无活性的Fv；并且其中所述第一可变轻结构域和所述第一伪可变重结构域分子间缔合以形成无活性的Fv。
在另外的方面，形式3A和形式3B蛋白质具有sdABD-HSA，所述sdABD-HSA具有SEQID NO:45。
在进一步的方面，形式3A和形式3B蛋白质具有结合至选自EGFR、EpCAM、FOLR1和B7H3的TTA的sdABD-TTA。所述sdABD-TTA可选自由以下组成的组：SEQ ID NO:1、SEQ ID NO:5、SEQ ID NO:9、SEQ ID NO:13、SEQ ID NO:17、SEQ ID NO:21、SEQ ID NO:25、SEQ ID NO:29、SEQ ID NO:33、SEQ ID NO:37以及SEQ ID NO:41。
在进一步的方面，本发明提供了核酸组合物，所述核酸组合物包含编码前药对的第一蛋白质成员的第一核酸和编码所述前药对的第二蛋白质成员的第二核酸；以及含有所述核酸的表达载体和宿主细胞。
V.附图说明
图1描绘本发明的“形式1”类型的蛋白酶活化，其在本文中称为“受约束的、可裂解的构建体”或“cc构建体”。在这个实施方案中，代表性构建体是Pro140：存在针对两种TTA的ABD(如图1中所描绘，这两者是相同的，但是如本文所述，它们可以不同)。在裂解后，前药构建体分裂成三种组分，一种含有经由结构域接头连接至αCD3的活性VH的α-TTA结构域，第二种含有经由结构域接头连接至αCD3的活性VL的α-TTA结构域，并且“剩余”部分包含连接至无活性的VH和VL的半衰期延长结构域。这两个活性可变结构域然后自由缔合以形成功能性抗CD3结合结构域。应注意，在“形式1”实施方案中，所得的活性组分是三价的：存在与CD3的单价结合和与TTA的二价结合，从而产生双特异性结合蛋白，尽管在一些情况下这种三价可以是三特异性的：具有与CD3的单价结合、与第一TTA的单价结合和与第二TTA的单价结合。图1还示出抗人血清白蛋白(HSA)结构域，其为半衰期延长结构域，在许多实施方案中为如本文所定义的sdABD，尽管如本文所论述，但这是任选的，并且/或者可被其他半衰期延长结构域替代；另外，所述半衰期延长结构域也可在构建体的N末端或内部。图1还具有Fv的VH和VL以及伪Fv的iVH和iVL，它们处于特定的顺序，例如从N-末端至C-末端为VH-接头-VL(和iVL-接头-iVH)，尽管如本领域技术人员将认识到的，这些顺序可颠倒(VL-接头-VH和iVH-接头-iVL)。可替代地，这些Fv中的一个可处于一个取向，而另一个处于另一取向，尽管处于如此处所示的取向的蛋白质的表达出人意料地高于其他取向。
图2描绘本发明的“形式2”类型的蛋白酶活化，其在本文中称为“受约束的、不可裂解的构建体”或“CNCL构建体”，在本文中有时也称为如本文所论述的“二聚化构建体”。这些构建体未如本文所论述的那样异构化。在裂解后，两个前药构建体分裂成四个组分，即，两个连接至两个伪结构域(其可能能够或可能不能够自缔合，这取决于接头的长度和失活突变)的半衰期延长结构域(在这种情况下为针对HSA的sdABD)，以及两个活性部分，所述两个活性部分自组装成二聚体活性部分，所述二聚体活性部分含有四个抗TTA结构域(其可全部相同，或者两个相同，而另外两个不同)。应注意，在“形式2”实施方案中，所得的活性组分是六价的：存在与CD3的二价结合和与TTA的四价结合，从而产生双特异性结合蛋白，尽管在一些情况下这种六价可以是三特异性的：具有与CD3的二价结合、与第一TTA的二价结合和与第二TTA的二价结合。图2还示出抗人血清白蛋白(HSA)结构域，其为半衰期延长结构域，在许多实施方案中为如本文所定义的sdABD，尽管如本文所论述，但这是任选的，并且/或者可被其他半衰期延长结构域替代；另外，所述半衰期延长结构域也可在构建体的N末端或内部。图2还具有Fv的VH和VL以及伪Fv的iVH和iVL，它们处于特定顺序，例如从N-末端至C-末端为VH-接头-VL(和iVL-接头-iVH)，尽管如本领域技术人员将认识到的，这些顺序可颠倒(VL-接头-VH和iVH-接头-iVL)。可替代地，这些Fv中的一个可处于一个取向，而另一个处于另一取向，尽管处于如此处所示的取向的蛋白质的表达出人意料地高于其他取向。
图3A-图3B描绘“形式3”类型的构建体，其有时也称为如本文概述的“半构建体”或“半-COBRATM”，因为这些构建体是共同构成MCE治疗剂的两条不同的多肽链，如本文进一步所论述。在此实施方案中，所述构建体成对递送，其中预先裂解的分子内自组装产生无活性的抗CD3 Fv结构域。在裂解后，惰性可变结构域被释放，两个活性可变结构域然后分子间组装以形成活性抗CD3结合结构域。该两种sdABD-TTA结合至肿瘤细胞表面上的相应受体，并且所述裂解通过蛋白酶进行。这允许分子间组装，因为所述分子在物理上被保持在适当位置，从而有利于活性抗CD3结构域的组装。如上文针对形式1和2所述的一样，在此实施方案中，可变结构域的N-末端至C-末端顺序也可颠倒或混合。此外，sdABD(HSA)可位于每个半构建体的N-末端或C-末端。Pro16在C末端具有sdABD(HSA)，而Pro17在N末端具有它(参见Pro19，SEQ ID NO:XX，在C-末端具有sdABD(HSA))。图3A示出每个半构建体具有单个sdABD-TTA结构域的形式3构建体，并且图3B示出每个半构建体具有两个sdABD-TTA的形式3构建体，所述两个sdABD-TTA呈“双重靶向”或“异质靶向(hetero-targeting)”形式。注意，图3B使用FOLR1和EGFR作为两个TTA，但是也可使用如本文概述的其他组合。
图4描绘类似于“形式2”构建体、但只有单个sdABD-TTA的“形式4”类型的构建体。该图示出针对EGFR的sdABD-TTA，但是如本领域技术人员将理解的，也可使用其他TTA。在裂解后，前药构建体分裂成两个组分，即，连接至伪Fv的半衰期延长结构域(在这种情况下为针对HSA的sdABD)，以及活性部分，所述活性部分在来自不同的被裂解分子的第二活性部分存在的情况下自组装成含有两个抗TTA结构域的二聚活性部分。应注意，在“形式4”实施方案中，所得的活性组分是四价的：存在与CD3的二价结合和与TTA的二价结合，从而产生双特异性结合蛋白。图4还示出抗人血清白蛋白(HSA)结构域，其为半衰期延长结构域，在许多实施方案中为如本文所定义的sdABD(1/2)，尽管如本文所论述，但是这是任选的，并且/或者可被其他半衰期延长结构域替代；另外，所述半衰期延长结构域也可在构建体的N末端或内部。图4还具有Fv的VH和VL以及伪Fv的iVH和iVL，它们处于特定顺序，例如从N-末端至C-末端为VH-接头-VL(和iVL-接头-iVH)，尽管如本领域技术人员将认识到的，这些顺序可颠倒(VL-接头-VH和iVH-接头-iVL)。可替代地，这些Fv中的一个可处于一个取向，而另一个处于另一取向，尽管处于如此处所示的取向的蛋白质的表达出人意料地高于其他取向。
图5A–图5G描绘本发明的多个序列。对于抗原结合结构域，CDR加有下划线。如本文更全面地概述的，这些结构域可以以本发明中各种各样的构型(包括“形式1”、“形式2”、“形式3”和“形式4”取向)来组装。值得注意的是，SEQ ID NO:90被MMP9裂解的速度稍微快于SEQID NO:75和76被裂解的速度，并且SEQ ID NO:91被裂解的速度慢于SEQ ID NO:75和76被裂解的速度。
图6A–图6B描绘许多适合的蛋白酶裂解位点。如本领域技术人员将理解的，这些裂解位点可用作可裂解的接头。在一些实施方案中，例如，当需要更柔性的可裂解接头时，在这些裂解位点的N-末端和C-末端中的一者或两者处可存在另外的氨基酸(通常是甘氨酸和丝氨酸)。
图7A–图7D描绘与“形式3”或“半-COBRATM”结构相关的一些数据。这表明形式3构建体在被蛋白酶(在这种情况下为EK蛋白酶，但是可使用本文中概述和图5和图6中描绘的任何蛋白酶裂解位点)裂解后协同地结合至CD3并且产生CD3结合位点，如通过夹心FACS分析所示。
图8A–图8D显示，蛋白酶裂解利用互补的半-COBRATM对协同地活化T细胞对EGFR+靶细胞的杀伤。图8A和图8B显示，处于隔离状态、但是用不同浓度的蛋白酶裂解的构建体对靶细胞活力没有影响。然而，图8C显示，在组合在一起时，在蛋白酶存在下，靶细胞活力显著降低。图8D示出一般机制。
图8示出用于在测试形式1构建体的功效的测定中使用的一些非靶标对照。
图9A-图10F显示，活性CD3结合结构域的产生取决于两个“臂”(例如sdABD-TTA结构域)的靶结合，这两“臂”中的一者在两个构建体中的每一个上。如实施例中所述的那样进行TDCC测定。
图10示出适合的半-COBRATM对的示意图。“Mep”代表穿膜肽酶蛋白酶裂解位点，“His-6”是如本文更充分论述的标签，ST14是蛋白裂解酶蛋白酶裂解位点，并且“Thb”是凝血酶蛋白酶裂解位点。
图11A-图12C示出与图10的构建体相关联的TDCC数据。图11A显示预先裂解的半-COBRA对的添加对OvCAR8细胞产生功效，图11B显示预先裂解的半-COBRA对的添加对HCT116细胞产生功效，并且图11C显示预先裂解的半-COBRA对的添加对LoVo细胞产生功效，这些细胞全都是癌细胞系。
图12A–图13B显示，MMP9接头在体内是稳定的。经由尾静脉以0.5mg/kg的剂量水平向NSG小鼠施用单次静脉内推注剂量的任一Pro40(MMP9可裂解)、Pro74(不可裂解)。在25mM柠檬酸、75-mM L-精氨酸、75mM NaCl和4％蔗糖pH 7.0的媒介物中制备每种化合物的剂量溶液。在预先选择的时间从每只动物采集两个血液样品，一个血液样品在研究开始时通过眼眶出血或下颌下出血采集，而另一个血液样品在终点时间点通过心脏穿刺采集。血液采集的时间点是0.083、1、6、24、72和168小时。使用K2 EDTA管由每个单独的血液样品制备血浆。使用MSD测定利用对抗HSA sdABD有特异性的MAb确定浓度并用EGFR细胞外结构域进行检测。
图13描绘在图14中所描绘的实验中使用的形式3A半-COBRATM构建体的示意图。Pro51是阳性对照，因为它“始终在运行(always on)”，这是因为它形成了活性抗CD3 Fv。Pro98是阴性对照，因为它的sdABD是针对不能被肿瘤表达的鸡卵溶菌酶。Pro77和Pro53是使用针对EGFR的sdABD和MMP9裂解位点的前药形式3A对。Pro74和Pro72是阴性对照形式3A对，因为它们没有裂解位点。
图14显示，在使用利用实施例中的方案植入到小鼠中的两种不同的肿瘤细胞系时，形式1构建体在体内消退肿瘤。半-COBRA构建体(Pro77和Pro53)的抗肿瘤活性取决于对抗EGFR sdABD和MMP9可裂解接头二者的纳入，以及活性抗CD3 Fv。
图15示出下一代形式的示意图，所述下一代形式，即，具有两个伪Fv结构域(它们之间具有可裂解位点)的全长构建体，如US2018/0134789中大体描述的，所述专利据此以引用的方式并入。但是，如下图所示，这种第一代全长构建体未显示出非常好的条件性，因为它可异构化形成活性和非活性构建体。
图16显示，形式3A构建体对实际上显示出比Pro100第一代全长构建体更好的条件性。
图17描绘另外的第一代全长构建体，所述构建体在图18中进行了测试。
图18显示，该第一代构建体即使在未裂解的形式下也显示出高活性，例如较差条件性。
图19显示，第一代全长构建体在分析SEC上显示出两个单体峰。
图20示出非裂解活性的原因的示意图，所述原因是全长第一代构建体异构化形成两种构象，一种构象因为没有形成活性抗CD3 Fv而无活性(“二价scFv”)，而另一种构象在不存在蛋白酶的情况下具有活性(“单链双抗体”类型的构型)。参见PEDS 23(8):667-677(2010)。
图21示出在利用第一代单链构建体的情况下在37C下运行2天的TDCC测定的结果。结果表明，未裂解的构建体显示出强大的杀伤作用。这些结果导致形式1构建体的产生。
图22A-图23G示出本发明中使用的形式1构建体。如本领域技术人员将理解的并且在本文中所描述的，虽然这些被描绘为具有sdABD-EGFR靶向部分，但是可使用针对其他TTA的sdABD。
图23显示，形式1构建体(在这种情况下为Pro140)形成在37C下稳定的单一异构体。
图24描绘了如通过Octet测定所测量，形式1构建体在未裂解形式下与人CD3的结合力非常低。顶部线是Pro120，中间线是Pro51(阳性对照)，并且底部线是在4C或37C下保持3天的Pro140。
图25类似地描绘了形式1构建体在未裂解形式下具有非常低的TDCC活性。
图26描绘了在体内测试中使用的特定形式1构建体Pro140，其使用sdABD-EGFR作为靶向部分并且使用MMP9裂解位点。
图27A-图28B示出使用形式1构建体时的肿瘤消退。
图28描绘了由于受约束的Fv中的裂解位点，可产生若干不同的片段：部分裂解的片段和完全裂解的片段。出人意料地，部分裂解的形式比完全裂解的形式更具活性，从而导致形式2的产生。
图29示出许多形式2示意图，它们全部使用sdABD-EGFR靶向结构域，但是如本文所概述和序列中所列出的，可使用针对其他TTA的sdABD。Pro51和Pro201是阳性对照(处于活性“半”构型)，而Pro214是全长阴性对照，因为不存在裂解位点。
图30示出使用穿膜肽酶裂解位点的形式2构建体Pro187的TDCC活性。TDCC测定中的Pro187在预先裂解的形式添加时的活性比以未裂解的形式添加时的活性高1200倍。预先裂解的Pro187展现出落在阳性对照Pro51与Pro201之间的活性。未裂解的Pro187展现出类似于不含蛋白酶可裂解接头的Pro214的活性。
图31示出使用n个MMP9裂解位点的形式2构建体Pro186的TDCC活性。TDCC测定中的Pro186在以预先裂解的形式添加时的活性比以未裂解的形式添加时的活性高18倍。预先裂解的Pro186展现出落在阳性对照Pro51与Pro201之间的活性。未裂解的Pro186展现出比不含蛋白酶可裂解接头的Pro214更高的活性。
图32描绘了Pro186构建体结合至具有不同水平的EGFR受体的细胞，其中CHO细胞在细胞表面上不表达EGFR。Pro186使表达不同水平的EGFR的细胞在相似COBRA浓度下达到饱和。
图33示出在图34的体内研究中使用的形式2构建体的示意图，该形式2构建体全部使用sdABD-EGFR靶向结构域。
图34显示，形式2构建体Pro186在两种浓度下均是高度有效的，并且在较低浓度下优于形式1构建体Pro140。
图35描绘基于Pro186、但具有不同蛋白酶裂解位点的许多形式2构建体。尽管所有这些构建体都将sdABD-EGFR用于两个靶向结构域，但也可使用其他针对不同TTA的sdABD，其可相同或不同。也就是说，均质靶向(两个靶向sdABD都针对同一TTA)或异质靶向(一个sdABD针对第一TTA，而另一个sdABD针对不同的TTA)都可以进行。
图36描绘改变Fv结构域之间的接头长度的不同形式2构建体的示意图。所示出的这些构建体使用了MMP9裂解位点，但是如本文所述也可使用其他裂解位点。类似地，尽管所有这些构建体都将sdABD-EGFR用于两个靶向结构域，但也可使用其他针对不同TTA的sdABD，它们可相同或不同。
图37显示伪Fv的接头长度可改变，例如在活性Fv之间具有短接头(“短活性”)且在伪Fv之间具有较长接头(“长无活性”)的形式2构建体表现出与“短活性”伴“短无活性”构建体相似的活性。因此，COBRA构建体的条件性不依赖于活性和无活性scFv接头两者都受约束；只要它们中的一者受约束即可，因为单链双抗体折叠似乎比二价scFv折叠更受欢迎。
图38示出活性Fv的接头长度可改变，例如，具有“长活性”和“短无活性”的形式2构建体表现得与具有“短活性”和“短无活性”的构建体相似。因此，COBRA构建体的条件性不依赖于活性和无活性scFv接头两者都受约束；只要它们中的一者受约束即可，单链双抗体折叠似乎比二价scFv折叠更受欢迎。
图39A-图40C示出许多不同构建体的示意图。Pro188是形式1构建体，其与Pro140相似，但在伪Fv中带有长接头(16聚体)。Pro189和Pro190(形式2构建体)与Pro186和Pro187相似，但在伪Fv结构域中具有长接头(16聚体)。Pro191和Pro192(同样形式2构建体)与Pro189和Pro190类似，但它们在sdABD(1/2)上游具有额外的裂解位点。Pro193(形式4)具有单个EGFR靶向结构域、被重排为处于相反顺序的iVH和iVL以及在sdABD(1/2)上游的额外裂解位点。Pro195是类似于Pro186的形式2构建体，其具有结合至同一TTA(即EGFR)、但结合至不同表位的靶向结构域。Pro196、Pro197和Pro198是具有重排可变结构域的形式2构建体。
图40描绘了这样的事实，即，针对人FOLR1的不同sdABD克隆显示出不同的杀伤作用。将结合至人FOLR1的Pro22型构建体(具有FLAG序列而不是NCL的Pro51)与针对许多细胞系家族的Pro22-EGFR构建体进行了比较。
图41描绘了四种sdABD-FOLR1构建体的示意图，其包括对以下的使用：使用sdABD-EGFR2(两个分子分子间缔合以形成两个针对CD3的活性Fv)的Pro201阳性对照，以及两种形式2测试品(即，使用h77.2 sdABD的Pro311和使用h59.3 sdABD的Pro312)，以及两个阴性对照(即，使用h77.2 sdABD的Pro299和使用h59.3 sdABD的Pro303)。
图42描绘用于FOLR/MMP9体内设计的形式2构建体的示意图。
图43示出Pro312构建体在体内的功效，并且证明MMP9可裂解接头是抗肿瘤活性所必需的。
图44描绘了使用针对人B7H3的sdABD(sdABD-B7H3)的一些形式的示意图，其包括阳性对照Pro244(使用sdABD-B7H3(hF7)(两个分子分子间缔合以形成两个针对CD3的活性Fv)，以及两种形式2测试品，Pro225(其为一种形式2构建体)，以及Pro295(其为缺少裂解位点的阴性对照)。
图45显示，Pro225与对照Pro295相比较具有高的条件性。
图46显示，使用穿膜肽酶接头的形式2构建体Pro373与Pro295相比较显示出高的条件性。
图47描绘了许多sdABD-B7H3(使用hF12序列)构建体，显示出使用sdABD-EGFR的Pro51阳性对照、使用sdABD-hF12 B7H3的Pro244阳性对照、测试构建体Pro226和不含裂解位点的阴性对照Pro296。
图48示出在TDCC测定中Pro226构建体的良好条件性。
图49示出sdABD针对人EpCAM的人源化。
图50示出许多形式的示意图：Pro22hVIB13和Pro205是阳性对照，Pro199是形式2构建体，并且Pro175是阴性对照。
图51示出sdABD-EpCAM构建体的TDCC活性，该构建体显示出良好的条件性。
图52A-图53B示出sdABD-EpCAM Pro199构建体的TDCC活性，该构建体在HT29和LoVo细胞模型中显示出良好条件性。
图53A–图54B示出sdABD-EpCAM Pro200构建体的TDCC活性，该构建体在HT29和LoVo细胞模型中显示出良好条件性。
图54示出Pro255与具有双重EpCAM sdABD的Pro199的比较的示意图，该Pro255使用两种不同的sdABD-TTA，一种sdABD-TTA是针对EGFR(sdABD-EGFR)，而另一种sdABD-TTA是针对EpCAM(sdABD-EpCAM)。这些有时在本文中称为“异质靶向”构建体，在这种情况下为形式2构建体。
图55显示，具有MMP9裂解位点的Pro255双重靶向分子显示出良好条件性。
图57A–图57D示出在三种不同细胞类型上的实验的结果。首先，产生具有相似的EpCAM、EGFR和EpCAM+EGFR表达水平的Raji转染子(数据未示出)。然后，使用每种细胞类型在TDCC测定中对靶向EpCAM和EGFR两者的Pro255进行了测试。图57A示出不表达任一受体的亲代Raji系。图57B示出在EpCAM系上的条件性。图57C示出在EGRF系上的条件性。图57D示出在EpCAM/EGFR系上的条件性。
图56描绘形式4构建体Pro258的示意图。
图57A–图59B显示，Pro258在FBS和人血清两者中都是条件性的。培养物中的MMP9活性导致MMP9接头的条件性被低估。令人感兴趣的是，Pro51 TDCC活性受HSA结合抑制，而Pro258 TDCC活性在HSA存在的情况下与Pro51相似。最后，Pro258条件性在HSA存在的情况下有所增强，增强了6倍。
图58A-图60C示出其他MMP对MMP9底物的裂解。
图59A–图61B示出一些示例性构建体及其形式。
图60A–图62U示出本发明的许多序列，但是在序列表中还发现了许多另外的序列。CDR加有下划线且加粗，接头加有双下划线(其中可裂解的接头呈斜体且加有双下划线)，并且结构域分隔用“/”表示。所有His6标签都是任选的，因为它们可用于降低人体内的免疫原性并且可为纯化标签。
VI.具体实施方式
A.引言
本发明涉及降低结合至诸如CD3和肿瘤抗原的重要生理靶标的双特异性抗体(包括抗体样功能性蛋白质)的毒性和副作用的方法。许多抗原结合蛋白(如抗体)可具有显著脱靶副作用，并且因此需要仅在疾病组织附近活化治疗分子的结合能力，以避免脱靶相互作用。因此，本发明涉及具有许多功能性蛋白质结构域的多价条件性有效(“MCE”)蛋白质。一般而言，这些结构域中的一个是将结合靶肿瘤抗原(TTA)的抗原结合结构域(ABD)，并且另一个是在某些条件下将结合T细胞抗原(如CD3)的ABD。另外，MCE蛋白还包括一个或多个蛋白酶裂解位点。即，治疗性分子被制备成“前药”样形式，其中CD3结合结构域在暴露于肿瘤环境之前是无活性的。肿瘤环境含有蛋白酶，使得在暴露于蛋白酶后，前药被裂解并变得具有活性。
这在本文一般通过使用包含针对T细胞抗原(如CD3)的“伪”可变重结构域和“伪”可变轻结构域的蛋白质来实现，所述蛋白质将MCE的CD3 Fv约束为如本文论述的无活性形式。由于TTA使MCE靶向到肿瘤附近区域，因此使MCE暴露于蛋白酶。在裂解后，活性可变重结构域和活性轻结构域现在能够配对以形成针对CD3的一个或多个活性ABD，并且因此将T细胞募集至肿瘤，从而进行治疗。
一般而言，CD3结合结构域(“Fv”)处于受约束的形式，其中传统上形成Fv的活性可变重结构域与活性可变轻结构域之间的接头太短以至于不允许这两个活性可变结构域彼此结合；这被称为“受约束的接头”；这些可以是受约束且可裂解的(CCL，如形式1中所用)或受约束且不可裂解的(CNCL，如形式2中所用)。相反，在前药(例如未裂解的)形式中，前药多肽还包含“伪Fv结构域”。伪Fv结构域包含具有标准框架区、但具有“惰性”或“非活性”CDR的可变重结构域和轻结构域。伪Fv结构域还在无活性可变重结构域与无活性可变轻结构域之间具有受约束的接头。由于空间约束，Fv和伪Fv结构域均不能自组装，因此由于各自的框架区的亲和力，存在使aVL与iVH配对以及使aVH与iVL配对的分子内组装。然而，由于伪结构域的“惰性”CDR，所得ABD将不结合CD3，从而防止脱靶毒性。然而，在肿瘤中或附近存在蛋白酶的情况下，前药构建体被裂解，使得伪-Fv结构域从表面释放，并且因此允许“真实的”可变重结构域和可变轻结构域分子间缔合(例如两个裂解的构建体结合在一起)，从而触发活性CD3结合和所得肿瘤功效。这些构建体在本文中一般被称为条件性双特异性重定向活化构建体或“COBRATM”。分子内组装的稳定性被本文的条件性实验所证明，由此在不存在蛋白酶的情况下，未裂解的构建体不具有活性(例如，没有形成活性CD3结合结构域)。
令人感兴趣的是，为了便于描述，尽管这些构建体在本文中均被称为“受约束的”，但是另外的工作表明即使Fv结构域之一不受约束，例如，所述结构域之一可具有更长、柔性的接头，分子内组装也是有利的。也就是说，如图36、图37和图38中所示，如果仅一个Fv结构域(具有活性VL和VH的结构域或伪Fv结构域)受到约束，则分子内组装仍然发生(例如，未裂解的构建体在没有蛋白酶裂解存在的情况下是无活性的)。但是，在当前系统中，当两个接头均受约束时，所述蛋白质具有更好的表达。然而，如本领域技术人员将理解的，本文的形式1、形式2或形式4构建体中的任一种都可具有这些带有“不受约束的”或“柔性的”接头的Fv结构域之一。为便于参考，所示出的构建体的两个Fv结构域都处于受约束形式。
本发明的构建体和形式是相对于WO2017/156178中描述的发明的变化型式，所述专利特此明确地以引用的方式整体并入。如图20中所示，由于单个多肽中存在两组VH和VL结构域，所以先前构建体具有异构化的能力，从而形成二价scFv和单链双抗体。即使在纯化每种同种型之后，二价构建体仍可与双抗体同种型达到平衡。由于在没有蛋白酶裂解存在的情况下单链双抗体具有结合至CD3的能力，因此构建体的效用降低。
为了解决这个问题，本发明提供了四种单独类型的构建体来完成这种条件性活化。前药活化可以四种一般方式之一发生，如附图中总体上所示。在图1中，示出“形式1”机制。在此实施方案中，前药构建体具有两个裂解位点：一个在受约束的Fv的VH与vl结构域之间，从而释放出两个可变结构域以进行缔合；并且第二个在从前药构建体释放伪Fv结构域的位点，从而留下由于可变重结构域和可变轻结构域的先天自组装而缔合的两个分子，这两个分子各自还具有针对肿瘤抗原的抗原结合结构域，从而允许T细胞募集至肿瘤部位。
在替代实施方案中，前药构建体在在图2，“形式2”机制中示出。在此实施方案中，活性可变重链与活性轻链之间的结构域接头是受约束但不可裂解的接头(“CNCL”)。在前药形式中，受约束的伪Fv结构域的无活性VH和VL与受约束的Fv结构域的VH和VL缔合，使得不存在CD3结合。然而，一旦在肿瘤环境中发生裂解，两种不同的活化蛋白质(各自包含活性可变重结构域和轻结构域)就缔合以形成两个抗CD3结合结构域。
除了上文论述的“单链蛋白质”COBRA形式(其中所有组分都包含在单个氨基酸序列上)外，还存在依赖于成对起作用的两种蛋白质“半-COBRA”的构建体，如图3中所示。在此实施方案中，每种蛋白质具有被蛋白酶裂解位点隔开的一个活性可变结构域和一个惰性可变结构域。每个分子含有TTA结合结构域，使得当分子结合至TTA并暴露于肿瘤蛋白酶时，惰性结构域被裂解，并且两个活性可变结构域自组装以形成抗CD3结合结构域。
此外，本发明还提供了“形式4”构建体，如图4中所示。这些与“形式2”设计类似，除了使用针对TTA的单个ABD，使得在裂解后，两个前药分子现在形成含有两个活性抗CD3结构域的四价双特异性构建体，如在下文进一步描述。
因此，本发明的形式和构建体可用于治疗疾病。
B.定义
为了可更完全地理解本申请，以下提出若干定义。此类定义意在涵盖语法等效物。
本文中的“氨基酸”和“氨基酸同一性”意指20种天然存在的氨基酸或可能存在于特定、确定位置处的任何非天然类似物中的一种。在许多实施方案中，“氨基酸”是指20种天然存在的氨基酸之一。本文中的“蛋白质”意指至少两个共价附接的氨基酸，其包括蛋白质、多肽、寡肽和肽。
本文中的“氨基酸修饰”意指多肽序列中的氨基酸取代、插入和/或缺失或者针对化学地连接至蛋白质的部分的改变。例如，修饰可以是附接至蛋白质的经改变的碳水化合物或PEG结构。为了清楚起见，除非另有注释，否则氨基酸修饰总是针对由DNA编码的氨基酸，例如在DNA和RNA中具有密码子的20个氨基酸。本文优选的氨基酸修饰是取代。
本文中的“氨基酸取代”或“取代”意指亲本多肽序列中特定位置处的氨基酸被不同氨基酸替换。具体地，在一些实施方案中，取代是指非天然地存在于特定位置处的氨基酸，或者非天然地存在于生物体或任何生物体中的氨基酸。为了清楚起见，已被工程化以改变核酸编码序列、但不改变起始氨基酸(例如将CGG(编码精氨酸)更换成CGA(仍编码精氨酸)以增加宿主生物体表达水平)的蛋白质不是“氨基酸取代物”；也就是说，尽管产生了编码相同蛋白质的新基因，但如果蛋白质在其起始的特定位置处具有相同的氨基酸，则该蛋白质就不是氨基酸取代物。
如本文所用，“氨基酸插入”或“插入”意指在亲本多肽序列中特定位置处添加氨基酸序列。
如本文所用，“氨基酸缺失”或“缺失”意指在亲本多肽序列中特定位置处去除氨基酸序列。
如本文概述的，本发明的多肽特异性地结合至CD3和靶肿瘤抗原(TTA)，如靶细胞受体。“特异性结合”或“特异性地结合至特定抗原或表位”或“对特定抗原或表位具有特异性”意指明显不同于非特异性相互作用的结合。特异性结合可例如通过确定与对照分子结合相比的分子结合来测量，对照分子通常是不具有结合活性的类似结构的分子。例如，可通过与类似于标靶的对照分子竞争来确定特异性结合。
对特定抗原或表位的特异性结合可例如由抗体对抗原或表位的KD为至少约10-4M、至少约10-5M、至少约10-6M、至少约10-7M、至少约10-8、至少约10-9M、或者至少约10-10M、至少约10-11M、至少约10-12M或更高大来表现出来，其中KD是指特定抗体-抗原相互作用的解离速率。通常，特异地结合抗原的抗体的KD比对照分子对于所述抗原或表位的KD大20、50、100、500、1000、5,000、10,000或更高倍数。
此外，对特定抗原或表位的特异性结合可例如由抗体对于抗原或表位的KA或Ka比对于对照物的至少20、50、100、500、1000、5,000、10,000或更高倍数的抗体展现，其中KA或Ka是指特定抗体-抗原相互作用的缔合速率。结合亲和力通常使用本领域已知的Biacore测定或Octet来测量。
如本文所用，“亲本多肽”或“前体多肽”(包括Fc亲本或前体)意指随后被修饰以产生变体的多肽。所述亲本多肽可以是天然存在的多肽，或者天然存在的多肽的变体或工程化型式。亲本多肽可以指该多肽本身、包含亲本多肽的组合物，或编码亲本多肽的氨基酸序列。因此，如本文所用，“亲本Fc多肽”意指被修饰以产生变体的未修饰的Fc多肽，并且如本文所用的“亲本抗体”意指被修饰以产生变异抗体的未修饰的抗体。
如本文所用，“位置”意指在蛋白质的序列中的定位。位置可按顺序来编号，或根据既定形式，例如针对抗体编号的EU索引来编号。
如本文所用的“靶抗原”意指被给定抗体的可变区特异性地结合的分子。靶抗原可以是蛋白质、碳水化合物、脂质或其他化合物。本文描述了一系列合适的示例性靶抗原。
如本文所用的“靶细胞”意指表达靶抗原的细胞。一般而言，出于本发明的目的，靶细胞是表达TTA的肿瘤细胞或表达CD3抗原的T细胞。
如本文所用的“Fv”或“Fv结构域”或“Fv区”意指包含通常来自抗体的抗原结合结构域的VL和VH结构域的多肽。如果Fv结构域含有活性VH和VL结构域，则Fv结构域通常形成如本文所论述的“抗原结合结构域”或“ABD”(但是在一些情况下，使用含有受约束的接头的Fv，以使得活性ABD不会在裂解前形成)。如下文所论述，在本发明中，Fv结构域可以多种方式组构，并且可以是“活性的”或“无活性的”，如呈scFv形式、受约束的Fv形式、伪Fv形式等。应理解，在本发明中，在一些情况下，Fv结构域由单个多肽链上的VH和VL结构域组成，如图1和图2中所示，但具有受约束的接头，以使得不能形成分子内ABD。在这些实施方案中，正是在裂解后形成两个活性ABD。在一些情况下，Fv结构域由VH和VL结构域组成，所述VH和VL结构域中的一个是惰性的，以使得只有在裂解后才能形成分子间ABD。如下文所论述，在本发明中，Fv结构域可以多种方式组构，并且可以是“活性的”或“无活性的”，如呈scFv形式、受约束的Fv形式、伪Fv形式等。此外，如本文所论述的，含有VH和VL的Fv结构域可以是/形成ABD，并且不包含VH和VL结构域的其他ABD可使用sdABD来形成。
本文的“可变结构域”意指免疫球蛋白的区域，所述区域包含一个或多个Ig结构域，所述Ig结构域基本上由分别构成κ、λ以及重链免疫球蛋白基因座的任何Vκ、Vλ和/或VH基因编码。在一些情况下，可使用单个可变结构域，如sdFv(在本文也称为sdABD)。
在利用可变重(VH)结构域和可变轻(VL)结构域两者的实施方案中，每个VH和VL由以下列次序从氨基末端至羧基末端排列的三个高变区(“互补决定区”，“CDR”)和四个“框架区”或“FR”组成：FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4。因此，VH结构域具有结构vhFR1-vhCDR1-vhFR2-vhCDR2-vhFR3-vhCDR3-vhFR4，并且VL结构域具有结构vlFR1-vlCDR1-vlFR2-vlCDR2-vlFR3-vlCDR3-vlFR4。如本文更充分描述的，vhFR区和vlFR区自组装以形成Fv结构域。一般而言，在本发明的前药形式中，存在其中VH和VL结构域不能自缔合的“受约束的Fv结构域”，以及当自缔合时CDR不形成抗原结合结构域的“伪Fv结构域”。
高变区赋予抗原结合特异性并且通常涵盖来自以下的氨基酸残基：轻链可变区中的大约氨基酸残基24-34(LCDR1；“L”表示轻链)、50-56(LCDR2)和89-97(LCDR3)以及重链可变区中的大约31-35B(HCDR1；“H”表示重链)、50-65(HCDR2)和95-102(HCDR3)(Kabat等人,SEQUENCES OF PROTEINS OF IMMUNOLOGICAL INTEREST,第5版Public Health Service,National Institutes of Health,Bethesda,Md.(1991))，和/或形成高变环的那些残基(例如轻链可变区中的残基26-32(LCDR1)、50-52(LCDR2)和91-96(LCDR3)以及重链可变区中的残基26-32(HCDR1)、53-55(HCDR2)和96-101(HCDR3)；Chothia和Lesk(1987)J.Mol.Biol.196:901-917)。下面描述本发明的特定CDR。
如本领域技术人员将理解的，不同编号系统中CDR的确切编号和位置可以不同。然而，应理解，可变重和/或可变轻序列的公开内容包括相关(固有)CDR的公开内容。因此，每个可变重区的公开内容是vhCDR(例如vhCDR1、vhCDR2和vhCDR3)的公开内容，并且每个可变轻区的公开内容是vlCDR(例如vlCDR1、vlCDR2和vlCDR3)的公开内容。
CDR编号的有用比较如下，参见Lafranc等人,Dev.Comp.Immunol.27(1):55-77(2003):
表1
Figure BDA0002481085060000251
贯穿本说明书，当提及可变结构域中的残基(近似地，轻链可变区的残基1-107和重链可变区的残基1-113)时一般使用Kabat编号系统，而对于Fc区一般使用EU编号系统(例如Kabat等人,同上(1991))。
本发明提供了大量不同的CDR组。在这种情况下，在抗CD3组分背景下的“全CDR组”包含三个可变轻CDR和三个可变重CDR，例如vlCDR1、vlCDR2、vlCDR3、vhCDR1、vhCDR2和vhCDR3。如本领域技术人员将理解的，每组CDR，即VH和VL CDR，可单独地和作为一组结合至抗原。例如，在受约束的Fv结构域中，vhCDR可例如结合至CD3，并且vlCDR可结合至CD3，但是在受约束的形式中，它们不能结合至CD3。
在单结构域ABD(“sdABD”)，如在本文中一般被用来结合至靶肿瘤抗原(TTA)的单结构域ABD的背景下，CDR组仅有三个CDR；这些在本领域中有时也称为“VHH”结构域。
这些CDR可以分别是更大的可变轻结构域或可变重结构域的一部分。此外，如本文更全面概述的，在scFv序列的情况下，可变重结构域和可变轻结构域可在分开的多肽链上或在单个多肽链上，这取决于本文部分的形式和构型。
CDR促进抗原结合位点，或更具体地，表位结合位点的形成。“表位”是指与可变区中的称为互补位(paratope)的特定抗原结合位点相互作用的决定簇。表位是成组的诸如氨基酸或糖侧链的分子，并且通常具有特定结构特征，以及特定电荷特征。单一抗原可具有多于一个表位。
表位可包含直接参与结合的氨基酸残基(也称为表位的免疫显性组分)以及不直接参与结合的其它氨基酸残基，如会受到特定抗原结合肽所有效阻断的氨基酸残基；换句话说，氨基酸残基在特定抗原结合肽的足迹内。
表位可以是构象性表位或线性表位。构象性表位由来自线性多肽链的不同节段的空间上并列的氨基酸产生。线性表位由多肽链中相邻的氨基酸残基产生。构象性表位和非构象性表位的区别可能在于：对前者的结合在变性溶剂存在下会消失，而对后者的结合在变性溶剂存在下则不会消失。
表位通常包括至少3个、并且更通常至少5个或8-10个呈独特空间构象的氨基酸。识别同一表位的抗体可以通过显示出一种抗体阻断另一种抗体结合至靶标抗原的能力，例如“分箱(binning)”的能力的简单免疫测定来进行验证。如下文所概述，本发明不仅包括本文中列举的抗原结合结构域和抗体，而且包括竞争着与被所列举的抗原结合结构域结合的表位结合的那些。
本发明的可变重结构域和可变轻结构域可以是“活性的”或“无活性的”。
如本文所用，“无活性的VH”(“iVH”)和“无活性的VL”(“iVL”)是指伪Fv结构域的组分，其在分别与它们的同源VL或VH配偶体配对时形成VH/VL对，所得到的这种VH/VL对不能特异性地结合至“活性”VH或“活性”VL在与非无活性的类似VL或VH结合时将能够结合的抗原。示例性“无活性的VH”和“无活性的VL”结构域由野生型VH或VL序列的突变来形成，如下文更全面地概述。示例性突变在VH或VL的CDR1、CDR2或CDR3内。示例性突变包括将结构域接头置于CDR2内，从而形成“无活性的VH”或“无活性的VL”结构域。相比之下，“活性VH”或“活性VL”是这样的VH或VL，其在分别与其“活性”同源配偶体，即VL或VH配对后能够特异性地结合至其靶抗原。因此，应理解，伪Fv可以是VH/iVL对、iVH/VL对或iVH/iVL对。
相比之下，如本文所用，术语“活性”是指能够特异性地结合至CD-3的CD-3结合结构域。此术语在两种情况下使用：(a)当提及具有能够与其同源配偶体配对并特异性地结合至CD-3的序列的Fv结合对的单个成员(即VH或VL)时；和(b)当提及具有能够特异性地结合至CD-3的序列的同源物对(即，VH和VL)时。示例性“活性”VH、VL或VH/VL对是野生型或亲本序列。
“CD-x”是指分化(CD)蛋白簇。在示例性实施方案中，CD-x选自对施用了本发明多肽构建体的受试者中的T细胞的募集或活化具有作用的那些CD蛋白。在一个示例性实施方案中，CD-x是CD3，其序列显示于图5中。
结合本发明，术语“结合结构域”描述了这样的结构域，其(特异性地)与靶分子(抗原)上的给定靶表位或给定靶位点(例如：分别为EGFR和CD-3)结合/与所述给定靶表位或给定靶位点相互作用/识别所述给定靶表位或给定靶位点。靶抗原结合结构域(识别EGFR)的结构和功能，以及优选地CD-3结合结构域(识别CD3)的结构和/或功能是基于抗体(例如全长或整个免疫球蛋白分子，包括sdABD)的结构和/或功能。根据本发明，靶抗原结合结构域的特征通常为存在结合靶肿瘤抗原的三个CDR(在本领域中通常称为可变重结构域，尽管不存在相应的轻链CDR)。可替代地，针对TTA的ABD可包含三个轻链CDR(即VL区的CDR1、CDR2和CDR3)和/或三个重链CDR(即VH区的CDR1、CDR2和CDR3)。CD-3结合结构域优选还至少包含允许靶标结合的抗体的最低结构要求。更优选地，CD-3结合结构域包含至少三个轻链CDR(即VL区的CDR1、CDR2和CDR3)和/或三个重链CDR(即VH区的CDR1、CDR2和CDR3)。设想在示例性实施方案中，靶抗原和/或CD-3结合结构域通过噬菌体展示或文库筛选方法产生或者可通过噬菌体展示或文库筛选方法获得。
如本文所用，“结构域”意指具有功能的蛋白质序列，如本文所概述。本发明的结构域包括肿瘤靶抗原结合结构域(TTA结构域)、可变重结构域、可变轻结构域、接头结构域和半衰期延长结构域。
本文中的“结构域接头”意指联接如本文所概述的两个结构域的氨基酸序列。结构域接头可以是可裂解的接头、受约束的可裂解的接头、不可裂解的接头、受约束的不可裂解的接头、scFv接头等。
本文中的“可裂解的接头”(“CL”)意指可被如本文概述的疾病组织中的蛋白酶，优选人蛋白酶裂解的氨基酸序列。可裂解的接头通常长度为至少3个氨基酸，其中4、5、6、7、8、9、10、11、12、13、14、15或更多个氨基酸可用于本发明，这取决于所需的柔韧性。许多可裂解的接头序列见于图6和图5。
本文中的“不可裂解的接头”(“NCL”)意指在正常生理条件下不能被人蛋白酶裂解的氨基酸序列。
本文中的“受约束的可裂解的接头”(“CCL”)意指含有蛋白酶裂解位点(如本文所定义)的短多肽，其联接如本文所概述的两个结构域，使得该两个结构域不能彼此显著相互作用直到它们驻留在不同的多肽链上后，例如在裂解后。当CCL联接如本文定义的VH和VL结构域时，由于分子内方式中的空间限制，VH和VL在裂解前不能自组装形成功能性Fv(但是它们可以以分子间方式组装成伪Fv结构域)。在被相关蛋白酶裂解后，VH和VL可以分子间方式组装形成活性抗原结合结构域。一般而言，CCL的长度小于10个氨基酸，其中9、8、7、6、5和4个氨基酸可用于本发明。一般而言，蛋白酶裂解位点的长度通常为至少4+个氨基酸，以赋予足够的特异性，如图6中所示。
本文中的“受约束的不可裂解的接头”(“CNCL”)意指这样的短多肽，其联接如本文所概述的两个结构域，使得该两个结构域彼此显著相互作用并且在生理条件下不被人蛋白酶显著裂解。
本文中的“受约束的Fv结构域”意指这样的Fv结构域，其包含活性可变重结构域和活性可变轻结构域，所述活性可变重结构域和活性可变轻结构域与本文所概述的受约束接头共价连接，使得活性重和轻可变结构域不能分子内相互作用以形成将结合抗原(如CD3)的活性Fv。因此，受约束的Fv结构域是类似于scFv、但是由于受约束的接头的存在而不能结合抗原的Fv结构域(但是它们可与惰性可变结构域分子间组装以形成伪Fv结构域)。
本文中的“伪Fv结构域”意指包含使用结构域接头(其可以是可裂解的、受约束的、不可裂解的、非受约束的等)连接的伪或无活性可变重结构域或者伪或无活性可变轻结构域的结构域。伪Fv结构域的iVH和iVL结构域在彼此缔合(iVH/iVL)时或者在与活性VH或VL缔合时不结合至人抗原；因此，iVH/iVL、iVH/VL和iVL/VH Fv结构域不明显结合至人蛋白质，以使得这些结构域在人体中是惰性的。
本文中的“单链Fv”或“scFv”意指通常使用如本文所论述的结构域接头共价附接至可变轻(VL)结构域以形成scFv或scFv结构域的可变重(VH)结构域。scFv结构域可位于从N-末端至C-末端(VH-接头-VL或VL-接头-VH)的任一个取向上。
本文中的“单结构域Fv”、“sdFv”或“sdABD”意指通常基于骆驼科动物抗体技术的仅具有三个CDR的抗原结合结构域。参见：Protein Engineering 9(7):1129-35(1994)；RevMol Biotech 74:277-302(2001)；Ann Rev Biochem 82:775-97(2013)。如本文所概述，本文使用两种通用类型的sdABD：结合至TTA并被这样注释的sdABD(对于通用术语为sdABD-TTA，或对于结合至EGFR的那种为sdABD-EGFR，对于结合至FOLR1的那种为sdABD-FOLR1)和结合至HSA的sdABD(“sdABD-HSA”或“sdABD(1/2)”)。
“蛋白酶裂解位点”是指被蛋白酶识别并裂解的氨基酸序列。适合的蛋白酶裂解位点在下文概述且在图5和图6中示出。
如本文所用，“蛋白酶裂解结构域”是指这样的肽序列，其掺入有“蛋白酶裂解位点”以及介于各个蛋白酶裂解位点之间以及介于一个或多个蛋白酶裂解位点与本发明构建体的其他功能组分(例如，VH、VL、iVH、iVL、一个或多个靶抗原结合结构域、半衰期延长结构域等)之间的任何接头。如本文所概述，蛋白酶裂解结构域还可在必要时包含另外的氨基酸，例如以赋予柔韧性。
术语“COBRATM”和“条件性双特异性重定向活化”是指具有许多功能性蛋白质结构域的双特异性条件性有效的蛋白质。在一些实施方案中，功能性结构域之一是结合靶肿瘤抗原(TTA)的抗原结合结构域(ABD)。在某些实施方案中，另一个结构域是在某些条件下结合至T细胞抗原的ABD。T细胞抗原包括但不限于CD3。术语“半-COBRATM”是指这样的条件性有效的蛋白质，其由于集中在靶标表达细胞的表面上时先天自组装而在半-COBRA的可变重链可与另一个半-COBRATM(互补的半-COBRATM)的可变轻链缔合时可结合T细胞抗原。
VII.本发明的融合蛋白
本发明的融合蛋白具有以多种方式连接在一起的许多不同的组分(在本文中通常称为结构域)。所述结构域中的一些是结合结构域，所述结合结构域各自结合至靶抗原(例如，TTA或CD3)。由于它们结合至多于一种抗原，因此在本文中它们被称为“多特异性”；例如，本发明的前药构建体可结合至TTA和CD3，并且因此是“双特异性的”。蛋白质也可具有更高的特异性；例如，如果第一αTTA结合至EGFR，第二αTTA结合至EpCAM，并且存在抗CD3结合结构域，则这将是“三特异性”分子。类似地，向此构建体添加抗HSA结合结构域将是“四特异性的”，如图3B所示。
如本领域技术人员将理解的，本发明的蛋白质可具有不同的化合价并且是多特异性的。即，本发明的蛋白质可结合具有多于一个结合位点的靶标；例如，Pro140对于EGFR是二价的。
本发明的蛋白质可包括以如本文概述的多种方式排列的CD3抗原结合结构域、肿瘤靶标抗原结合结构域、半衰期延长结构域、接头等。
A.CD3抗原结合结构域
T细胞应答的特异性由T细胞受体复合物对抗原(在主要组织相容性复合物MHC的背景下展示的抗原)的识别来介导。作为T细胞受体复合物的一部分，CD3是包含存在于细胞表面的CD3γ(gamma)链、CD3δ(delta)链、两条CD3e(epsilon)链和两条CD3ζ(zeta)链的蛋白质复合物。CD3分子与T细胞受体(TCR)的α(alpha)和β(beta)链缔合以构成TCR复合物。CD3在T细胞上的簇集(诸如通过结合至CD3的Fv结构域进行的簇集)导致T细胞活化，类似于T细胞受体的参与，但不依赖其克隆特有的特异性。
然而，如本领域中已知的，CD3活化可引起许多毒性副作用，并且因此，本发明涉及仅在存在其中发现了特定蛋白酶的肿瘤细胞存在下提供本发明多肽的活性CD3结合，所述蛋白酶然后裂解本发明的前药多肽以提供活性CD3结合结构域。因此，在本发明中，抗CD-3Fv结构域与CD-3的结合由蛋白酶裂解结构域调控，所述蛋白酶裂解结构域仅在蛋白酶水平升高的患病细胞或组织的微环境中(例如在本文所述的肿瘤微环境中)限制CD-3Fv结构域与CD-3的结合。
因此，本发明提供了两组VH和VL结构域，即活性组(VH和VL)和无活性组(iVH和iVL)，所有四者都存在于前药构建体中。对所述构建体的形式进行设置，以使得VH和VL组不能自缔合，而是与无活性配偶体(例如，如本文所示的iVH和VL以及iVL和VH)缔合。
1.活性抗CD3可变重结构域和可变轻结构域
存在许多本领域已知的可用于本发明的适合的活性CDR组和/或VH和VL结构域。例如，CDR和/或VH和VL结构域源自已知的抗CD-3抗体，例如像莫罗单抗-CD-3(OKT3)、奥西珠单抗(TRX4)、替普利珠单抗(MGA031)、维西珠单抗(Nuvion)、SP34或I2C、TR-66或X35-3、VIT3、BMA030(BW264/56)、CLB-T3/3、CRIS7、YTH12.5、F111-409、CLB-T3.4.2、TR-66、WT32、SPv-T3b、11D8、XIII-141、XIII-46、XIII-87、12F6、T3/RW2-8C8、T3/RW2-4B6、OKT3D、M-T301、SMC2、F101.01、UCHT-1以及WT-31。
在一个实施方案中，形成结合至人CD3的活性Fv结构域的VH和VL序列在图5中示出。如本文所示，这些活性VH(“aVH”)和活性VL(“aVL”)结构域可以不同的构型和形式1、2、3和4使用。
2.无活性的抗CD3可变重结构域和可变轻结构域
无活性的iVH和iVL结构域含有允许缔合的“常规”框架区(FR)，以使得无活性的可变结构域将与活性可变结构域缔合，从而使所述对无活性，例如不能结合CD3。
如本领域技术人员将理解的，存在许多可用于本发明中的“无活性”可变结构域。基本上，可使用具有允许与另一个可变结构域自组装的人框架区的任何可变结构域，无论可变区中CDR位置中的氨基酸是什么。为了清楚起见，无活性结构域被说成包含CDR，尽管从技术上说无活性可变结构域不赋予结合能力。
如本领域中将认识到的，产生无活性的VH或VL结构域通常很简单，并且可以多种方式完成。在一些实施方案中，通常通过改变活性Fv的一个或多个CDR(包括改变活性可变结构域的三个CDR中的一个或多个)来完成无活性可变结构域的产生。这可通过在一个或多个CDR中的功能上重要的残基处制造一个或多个氨基酸取代、用随机序列置换一些或所有CDR残基、用标签或flag序列置换一个或多个CDR,和/或将CDR和/或可变区与来自不相关抗体的CDR和/或可变区(例如，针对不同生物体的蛋白质的CDR和/或可变区)交换来完成。
在一些情况下，可变区中的CDR中仅一个可被改变以使其无活性，但是其他实施方案包括1、2、3、4、5或6个CDR的改变。
在一些情况下，无活性结构域可被工程改造成促进前药形式的选择性结合，以促进在裂解之前形成分子内iVH-VL和VH-iVL结构域(例如，越过分子间对形成)。参见例如Igawa等人Protein Eng.Des.Selection 23(8):667-677(2010)，特此明确地以引用的方式并入全部内容，特别是关于界面残基氨基酸取代的内容。
在某些实施方案中，本文所述的多肽构建体的CD-3结合结构域不仅显示出与人CD-3具有强有力的CD-3结合亲和力，而且还显示出与相应食蟹猴CD-3蛋白具有优异交叉反应性。在一些例子中，多肽构建体的CD-3结合结构域与来自食蟹猴的CD-3交叉反应。在某些例子中，针对CD-3的人:食蟹猴KD比率在5与0.2之间。
在一些实施方案中，抗原结合蛋白的CD-3结合结构域可以是结合至CD-3的任何结构域，包括但不限于来自单克隆抗体、多克隆抗体、重组抗体、人抗体、人源化抗体的结构域。在一些例子中，CD-3结合结构域源自最终将使用所述抗原结合蛋白的同一物种是有益的。例如，对于在人中使用，抗原结合蛋白的CD-3结合结构域包含来自抗体或抗体片段的抗原结合结构域的人或人源化残基可能是有益的。
因此，在一方面，抗原结合结构域包含人源化或人结合结构域。在一个实施方案中，所述人源化或人抗CD-3结合结构域包含本文所述的人源化或人抗CD-3结合结构域的一个或多个(例如，全部三个)轻链互补决定区1(LC CDR1)、轻链互补决定区2(LC CDR2)和轻链互补决定区3(LC CDR3)，和/或本文所述的人源化或人抗CD-3结合结构域的一个或多个(例如，全部三个)重链互补决定区1(HC CDR1)、重链互补决定区2(HC CDR2)和重链互补决定区域3(HC CDR3)，例如，包含一个或多个(例如，全部三个)LC CDR和一个或多个(例如，全部三个)HC CDR的人源化或人抗CD-3结合结构域。
在一些实施方案中，所述人源化或人抗CD-3结合结构域包含对CD-3具有特异性的人源化或人轻链可变区，其中所述对CD-3具有特异性的轻链可变区包含人轻链框架区中的人或非人轻链CDR。在某些例子中，轻链框架区是λ(lambda)轻链框架。在其他例子中，轻链框架区是κ(kappa)轻链框架。
在一些实施方案中，一个或多个CD-3结合结构域是人源化CD-3结合结构域或者全人CD-3结合结构域。在一些实施方案中，一个或多个活化的CD-3结合结构域与表达CD-3的细胞上的CD-3具有1000nM或更小的KD结合。在一些实施方案中，一个或多个活化的CD-3结合结构域与表达CD-3的细胞上的CD-3具有100nM或更小的KD结合。在一些实施方案中，一个或多个活化的CD-3结合结构域与表达CD-3的细胞上的CD-3具有10nM或更小的KD结合。在一些实施方案中，一个或多个CD-3结合结构域与食蟹猴CD-3具有交叉反应性。在一些实施方案中，一个或多个CD-3结合结构域包含本文提供的氨基酸序列。
在一些实施方案中，所述人源化或人抗CD-3结合结构域包含对CD-3具有特异性的人源化或人重链可变区，其中所述对CD-3具有特异性的重链可变区包含人重链框架区中的人或非人重链CDR。
在一个实施方案中，所述抗CD-3结合结构域是包含本文提供的氨基酸序列的轻链和重链的Fv。在一个实施方案中，所述抗CD-3结合结构域包含：轻链可变区，所述轻链可变区包含对本文提供的轻链可变区的氨基酸序列进行了至少一个、两个或三个修饰(例如，取代)、但不超过30、20或10个修饰(例如，取代)的氨基酸序列，或与本文提供的氨基酸序列具有95％-99％同一性的序列；和/或重链可变区，所述重链可变区包含对本文提供的重链可变区的氨基酸序列进行了至少一个、两个或三个修饰(例如，取代)、但不超过30、20或10个修饰(例如，取代)的氨基酸序列，或与本文提供的氨基酸序列具有95％-99％同一性的序列。在一个实施方案中，所述人源化或人抗CD-3结合结构域是scFv，并且包含本文所述的氨基酸序列的轻链可变区经由scFv接头附接至包含本文所述的氨基酸序列的重链可变区。scFv的轻链可变区和重链可变区可以例如处于任一以下取向：轻链可变区-scFv接头-重链可变区或重链可变区-scFv接头-轻链可变区。
在一些实施方案中，抗原结合蛋白的CD-3结合结构域对表达CD3的细胞上的CD-3具有亲和力，其KD为1000nM或更小、100nM或更小、50nM或更小、20nM或更小、10nM或更小、5nM或更小、1nM或更小或0.5nM或更小。在一些实施方案中，抗原结合蛋白的CD-3结合结构域对CD-3ε具有亲和力，其KD为1000nM或更小、100nM或更小、50nM或更小、20nM或更小、10nM或更小、5nM或更小、1nM或更小或0.5nM或更小。在进一步实施方案中，抗原结合蛋白的CD-3结合结构域对CD-3具有低亲和力，即约100nM或更大。
与CD-3结合的亲和力可例如通过抗原结合蛋白本身或其CD-3结合结构域与包被在测定板上的CD-3、展示在微生物细胞表面上的CD-3、处于溶液中的CD-3等结合的能力来确定，如本领域中已知的，通常使用Biacore或Octet测定来进行。可通过将配体(例如CD-3)或抗原结合蛋白本身或其CD-3结合结构域固定至珠粒、底物、细胞等上来测定本公开的抗原结合蛋白本身或其CD-3结合结构域与CD-3的结合活性。可在适当的缓冲液中添加剂，并且将结合配偶体在给定温度下孵育一段时间。在洗涤以除去未结合的材料之后，可用例如SDS、具有高pH的缓冲液等来释放被结合的蛋白质，并且例如通过表面等离子体共振(SPR)进行分析。
在许多实施方案中，优选的活性和惰性结合结构域是图5中所示的那些。
B.针对肿瘤靶抗原的抗原结合结构域
除了所描述的CD3和半衰期延长结构域之外，本文所述的多肽构建体还包含结合至一种或多种靶抗原或单种靶抗原上的一个或多个区域的靶结构域。本文中考虑了，本发明的多肽构建体例如在疾病特异性微环境中或在受试者的血液中在蛋白酶裂解结构域处被裂解，并且每个靶抗原结合结构域将结合至靶细胞上的靶抗原，从而活化CD3结合结构域以结合T细胞。一般而言，TTA结合结构域可在蛋白酶裂解之前结合至其靶标，因此它们可在靶细胞上“等待”被活化为T细胞衔接器。至少一种靶抗原参与疾病、病症或疾患和/或与疾病、病症或疾患相关联。示例性靶抗原包括与增生性疾病、肿瘤性疾病、炎性疾病、免疫病症、自身免疫性疾病、感染性疾病、病毒性疾病、过敏反应、寄生反应、移植物抗宿主病或宿主抗移植物病相关的那些。在一些实施方案中，靶抗原是肿瘤细胞上表达的肿瘤抗原。可替代地，在一些实施方案中，靶抗原与病原体(如病毒或细菌)相关。至少一种靶抗原也可针对健康组织。
在一些实施方案中，靶抗原是细胞表面分子，如蛋白质、脂质或多糖。在一些实施方案中，靶抗原是在肿瘤细胞、病毒感染的细胞、细菌感染的细胞、受损的红细胞、动脉斑块细胞或纤维化组织细胞上。
本发明的优选实施方案利用sdABD作为靶向结构域。这些相对于scFv ABD是优选的，因为将其他VH和VL结构域添加到本发明的构建体中可能使伪Fv结构域的形成复杂化。
在一些实施方案中，本发明的前药构建体利用，例如总体上在图3A中描绘为sdABD-TTA对，并在图4中描绘为“形式4”构型的单个TTA结合结构域。图4示出单一抗EGFRABD的使用，但是可使用其他TTA结合结构域。
在一些实施方案中，特别是在形式1和形式2构建体中，本发明的前药构建体利用两个TTA ABD，其再次优选呈sdABD-TTA形式。当使用双重靶向结构域时，它们可结合至同一TTA的同一表位。例如，如本文所论述，本文的许多构建体利用两个完全相同的靶向结构域。在一些实施方案中，可使用结合至同一TTA的不同表位的两个靶向结构域，例如，如图5中所示，两个EGFR sdABD结合至人EGFR上的不同表位。在一些实施方案中，所述两个靶向结构域结合至不同的TTA，参见例如图54。
本文考虑的多肽构建体包含至少一个抗原结合结构域，其中所述抗原结合结构域结合至至少一种靶抗原。在一些实施方案中，所述靶抗原结合结构域特异性地结合至细胞表面分子。在一些实施方案中，所述靶抗原结合结构域特异性地结合至肿瘤抗原。在一些实施方案中，所述靶抗原结合结构域特异性地且独立地结合至选自以下中的至少一种的肿瘤靶抗原(“TTA”)：EpCAM、EGFR、HER-2、HER-3、cMet、LyPD3、B7H3、CEA和FOLR1。
在本发明中特别有用的是针对人EGFR的sdABD，如图5中所示。
在本发明中使用的另外实施方案是针对人FOLR1的sdABD，如图5中所示。
本发明中使用的进一步实施方案是针对人B7H3的sdABD，如图5中所示。
在本发明中使用的另外实施方案是针对人EpCAM的sdABD，如图5中所示。
在一些实施方案中，所述蛋白质在蛋白酶裂解结构域裂解之前小于约100kDa。在一些实施方案中，所述蛋白质在蛋白酶裂解结构域裂解后是约25至约75kDa。在一些实施方案中，所述蛋白质在蛋白酶裂解之前具有高于针对首过清除的肾脏阈值的尺寸。在一些实施方案中，所述蛋白质在蛋白酶裂解之前具有至少约50小时的消除半衰期。在一些实施方案中，所述蛋白质在蛋白酶裂解之前具有至少约100小时的消除半衰期。在一些实施方案中，与针对同一靶抗原的IgG相比，所述蛋白质具有增加的组织渗透性。在一些实施方案中，与针对同一靶抗原的IgG相比，所述蛋白质具有增加的组织分布。
C.半衰期延长结构域
本发明的MCE蛋白(再次在本文中也称为“COBRATM”蛋白或构建体)任选地包含半衰期延长结构域。考虑了此类结构域包括但不限于HSA结合结构域、Fc结构域、小分子和本领域已知的其他半衰期延长结构域。
人血清白蛋白(HSA)(分子量约67kDa)是血浆中最丰富的蛋白质，以约50mg/ml(600uM)存在，并且在人中具有约20天的半衰期。HSA起到维持血浆pH值、促进胶体血压的作用，充当许多代谢产物和脂肪酸的载体，并且用作血浆中的主要药物转运蛋白。
与白蛋白的非共价缔合能延长短寿命蛋白质的消除半衰期。例如，与施用单独的Fab片段相比，当分别向小鼠和家兔静脉内施用时白蛋白结合结构域与Fab片段的重组融合体使得体内清除率降低至1/25和1/58且半衰期延长26和37倍。在另一个实例中，当胰岛素被脂肪酸酰化以促进与白蛋白的缔合时，在皮下注射至家兔或猪中时观察到持久的作用。这些研究在一起证明了白蛋白结合与延长的作用之间的联系。
在一方面，本文所述的抗原结合蛋白包含半衰期延长结构域，例如特异性地结合至HSA的结构域。在其他实施方案中，所述HSA结合结构域是肽。在进一步的实施方案中，所述HSA结合结构域是小分子。考虑了在一些实施方案中抗原结合蛋白的HSA结合结构域相当小并且不超过25kD、不超过20kD、不超过15kD，或不超过10kD。在某些例子中，如果HSA结合结构域是肽或小分子，则其为5kD或更小。
在许多实施方案中，半衰期延长结构域是来自结合至HSA的单结构域抗体的单结构域抗原结合结构域。此结构域在本文中通常被称为针对人HSA的“sdABD”(sdABD-HSA)，或可替代地称为“sdABD(1/2)”，以将这些结合结构域与针对TTA的sdABD区分开。特别有用的sdABD(1/2)在图5中示出。
抗原结合蛋白的半衰期延长结构域为抗原结合蛋白本身提供了改变的药效学和药代动力学。如上所述，半衰期延长结构域延长消除半衰期。半衰期延长结构域还改变药效学性质，包括改变抗原结合蛋白的组织分布、渗透和扩散。在一些实施方案中，与没有半衰期延长结合结构域的蛋白质相比，半衰期延长结构域提供改善的组织(包括肿瘤)靶向、组织渗透、组织分布、在组织内的扩散以及增强的功效。在一个实施方案中，治疗方法有效地且高效地利用减少量的抗原结合蛋白，从而产生降低的副作用，如降低的非肿瘤细胞细胞毒性。
进一步地，半衰期延长结构域，例如HSA结合结构域的特征包括HSA结合结构域对HSA的结合亲和力。可对所述HSA结合结构域的亲和力加以选择，以便在特定多肽构建体中达到特定消除半衰期目标。因此，在一些实施方案中，HSA结合结构域具有高结合亲和力。在其他实施方案中，HSA结合结构域具有中等结合亲和力。在其他实施方案中，HSA结合结构域具有低或微小的结合亲和力。示例性结合亲和力包括10nM或更小的KD浓度(高)、介于10nM与100nM之间的KD浓度(中等)，以及大于100nM的KD浓度(低)。如上所述，通过诸如表面等离子体共振(SPR)的已知方法来确定对HSA的结合亲和力。
D.蛋白酶裂解位点
如本文所概述，本发明的蛋白质组合物，特别是所述前药构建体包含通常位于可裂解的接头中的一个或多个蛋白酶裂解位点。
如本文所述，本发明的前药构建体包含至少一个蛋白酶裂解位点，所述至少一个蛋白酶裂解位点包含被至少一种蛋白酶裂解的氨基酸序列。在一些情况下，本文所述的MCE蛋白包含被至少一种蛋白酶裂解的1、2、3、4、5、6、7、8、9、10、11、12、13、14、15、16、17、18、19、20或更多个蛋白酶裂解位点。如本文中更充分论述的，当在前药构建中使用多于一个蛋白酶裂解位点时，所述蛋白酶裂解位点可以是相同的(例如，被单一蛋白酶裂解的多个位点)或不同的(被至少两种不同的蛋白酶裂解的两个或更多个裂解位点)。如本领域技术人员将理解的，含有三个或更多个蛋白酶裂解位点的构建体可利用一个，两个，三个等；例如一些构建体可利用针对两种不同蛋白酶的三个位点，等等。
蛋白酶裂解位点的氨基酸序列将取决于所针对的蛋白酶。如本领域中已知的，存在在体内发现并且可与疾病状态相关联的许多人蛋白酶。
已知蛋白酶由一些患病细胞和组织，例如肿瘤或癌细胞分泌，从而产生富含蛋白酶的微环境或蛋白酶丰富的微环境。在一些情况下，受试者的血液富含蛋白酶。在一些情况下，肿瘤周围的细胞将蛋白酶分泌到肿瘤微环境中。分泌蛋白酶的肿瘤周围的细胞包括但不限于肿瘤基质细胞、成肌纤维细胞、血细胞、肥大细胞、B细胞、NK细胞、调控性T细胞、巨噬细胞、细胞毒性T淋巴细胞、树突状细胞、间充质干细胞、多形核细胞以及其他细胞。在一些情况下，蛋白酶存在于受试者的血液中，例如靶向微生物肽中发现的氨基酸序列的蛋白酶。这种特征允许诸如抗原结合蛋白的靶向治疗剂具有另外的特异性，因为除了在靶细胞或靶组织的富含蛋白酶的微环境中之外，T细胞将不会被抗原结合蛋白结合。
蛋白酶是在一些情况下以序列特异性方式裂解蛋白质的蛋白质。蛋白酶包括但不限于丝氨酸蛋白酶、半胱氨酸蛋白酶、天冬氨酸蛋白酶、苏氨酸蛋白酶、谷氨酸蛋白酶、金属蛋白酶、天冬酰胺肽裂解酶、血清蛋白酶、组织蛋白酶(例如组织蛋白酶B、组织蛋白酶C、组织蛋白酶D、组织蛋白酶E、组织蛋白酶K、组织蛋白酶L、组织蛋白酶S)、激肽释放酶、hK1、hK10、hK15、KLK7、颗粒酶B、纤溶酶、胶原酶、IV型胶原酶、溶基质素、XA因子、胰凝乳蛋白酶样蛋白酶、胰蛋白酶样蛋白酶、弹性蛋白酶样蛋白酶、枯草杆菌蛋白酶样蛋白酶、猕猴桃蛋白酶、菠萝蛋白酶、钙蛋白酶、半胱天冬酶(例如半胱天冬酶-3)、Mir1-CP、木瓜蛋白酶、HIV-1蛋白酶、HSV蛋白酶、CMV蛋白酶、凝乳酶、肾素、胃蛋白酶、蛋白裂解酶、豆荚蛋白酶、疟原虫天冬氨酸蛋白酶(plasmepsin)、猪笼草蛋白酶(nepenthesin)、金属外肽酶、金属内肽酶、基质金属蛋白酶(MMP)、MMP1、MMP2、MMP3、MMP8、MMP9、MMP13、MMP11、MMP14、穿膜肽酶、尿激酶纤溶酶原活化因子(uPA)、肠激酶、前列腺特异性抗原(PSA，hK3)、白介素-1β转化酶、凝血酶、FAP(FAP-α)、二肽基肽酶和二肽基肽酶IV(DPPIV/CD26)。
一些适合的蛋白酶和蛋白酶裂解序列在图5和图6中示出。
E.接头
如本文所论述，本发明的不同结构域通常使用氨基酸接头连接在一起，所述氨基酸接头也可赋予包括柔性或刚性(例如空间约束)以及使用原位蛋白酶裂解的能力在内的功能性。这些接头可以许多方式分类。
本发明提供了“结构域接头”，所述结构域接头用于将两个或更多个结构域(例如VH和VL、靶肿瘤抗原结合结构域(TTABD，在本文中有时也称为“αTTA”(对于“抗TTA”而言))与VH或VL，半衰期延长结构域与另一种组分，等等)。结构域接头可以是，例如，不可裂解的(NCL)、可裂解的(“CL”)、受约束且可裂解的(CCL)，以及受约束且不可裂解的(CNCL)。
1.不可裂解的接头
在一些实施方案中，所述结构域接头是不可裂解的。一般来说，这些结构域接头可以是两种类型之一：不可裂解且柔性的，从而允许构建体中接头“上游”和“下游”的组分以某种方式分子内自组装；或不可裂解且受约束的，其中被接头分隔的两种组分不能分子内自组装。然而，应注意的是，在后一种情况下，尽管由不可裂解的受约束的接头分隔的两个组分结构域没有分子内自组装，但其他分子内组分将自组装以形成伪Fv结构域。
(i)不可裂解但柔性的接头
在此实施方案中，接头被用于联接结构域以保留结构域的功能性，这种联接一般通过不被患者体内的原位蛋白酶裂解的较长的柔性结构域来进行。适用于连接本发明多肽中的结构域的内部不可裂解的接头的实例包括但不限于(GS)n、(GGS)n、(GGGS)n、(GGSG)n、(GGSGG)n或(GGGGS)n，其中n是1、2、3、4、5、6、7、8、9或10。在一些实施方案中，接头的长度可以是约15个氨基酸。
(ii)不可裂解且受约束的接头
在一些情况下，所述接头不含裂解位点，并且也太短以至于不允许被接头分隔的蛋白质结构域分子内自组装，并且是“受约束的不可裂解的接头”或“CNCL”。例如，在Pro186中，活性VH和活性VL被8个氨基酸(“8聚体”)分隔开，所述8个氨基酸不允许VH和VL自组装成活性抗原结合结构域。在一些实施方案中，所述接头仍然是柔性的；例如，(GGGS)n，其中n＝2。在其他实施方案中，尽管通常不太优选，但是可使用更刚性的接头，如包括脯氨酸或大体积氨基酸的那些。
2.可裂解的接头
本文所有的前药构建体均包含至少一个可裂解的接头。因此，在一个实施方案中，结构域接头是可裂解的(CL)，在本文中有时称为“蛋白酶裂解结构域”(“PCD”)。在此实施方案中，CL含有蛋白酶裂解位点，如本文所概述且如图5和图6中所描绘的。在一些情况下，CL仅含有蛋白酶裂解位点。任选地，取决于裂解识别位点的长度，在CL的N-末端或C-末端中的一者或两者处可存在额外的几个连接氨基酸；例如，在裂解位点的N-末端和C-末端中的一者或两者处可存在1、2、3、4或5个氨基酸。因此，可裂解的接头也可以是受约束的(例如8聚体)或柔性的。
在本发明中特别令人感兴趣的是MMP9可裂解的接头和穿膜肽酶可裂解的接头，特别是MMP9受约束的可裂解的接头和穿膜肽酶受约束的可裂解的接头。
VIII.本发明的结构域
本发明提供了本发明的前药多肽的许多不同形式。本发明提供了受约束的Fv结构域和受约束的伪Fv结构域。另外，本发明提供了多价条件性有效(“MCE”)的蛋白质，该蛋白质含有两个Fv结构域，但是为非异构化构建体。如本文所概述，这些可以是非异构化可裂解的形式或非异构化不可裂解的形式，尽管每个构建体均含有至少一个蛋白酶裂解结构域。
重要的是，虽然这两种结构域(Fv结构域和伪Fv结构域)在本文中均被称为“受约束的”，意味着如上文所论述以及如图36、图37和图38中所示，但是这些中的仅一个需要受约束，尽管一般来说，当这两个接头都受约束时，蛋白质具有更好的表达。
本领域技术人员将理解，对于形式1、2和4，本发明的受约束的Fv结构域和伪Fv结构域的N-末端至C-末端顺序存在四种可能性(未示出接头)：aVH-aVL和iVL-iVH，aVH-aVL和iVH-iVL，aVL-aVH和iVL-iVH，aVL-aVH和iVH-iVL。所有四种都已进行测试，并且所有四种都具有活性，但是第一顺序aVH-aVL和iVL-iVH表现出比其他三种更好的表达。因此，虽然本文的描述一般以这种aVH-aVL和iVL-iVH形式示出，但本文的所有公开内容也包括这些结构域的其他顺序。
注意，一般而言，本发明的全长构建体的N-末端至C-末端顺序是基于aVH-aVL和iVL-iVH取向。
另外，本领域已知人中可能存在源自某些ABD的C-末端序列的免疫原性。因此，一般而言，特别是当构建体的C-末端终止于sdABD(例如，许多构建体的sdABD-HSA结构域)时，可使用组氨酸标签(His6或His10)。出于纯化原因，本文的许多或大多数序列使用His6 C-末端标签生成，但是这些序列也可用于降低人中的免疫原性，如Holland等人,DOI10.1007/s10875-013-9915-0和WO2013/024059中所示。
A.受约束的Fv结构域
本发明提供了受约束的Fv结构域，所述受约束的Fv结构域包含活性VH和活性VL结构域，所述活性VH和活性VL结构域使用受约束的接头(如本文所概述，所述受约束的接头可以是可裂解的(形式1和3)或不可裂解的(形式2和4))共价附接。受约束的接头在不存在裂解的情况下阻止aVH与aVL之间的分子内缔合。因此，受约束的Fv结构域一般包含可变结构域内所含的一组六个CDR，其中VH的vhCDR1、vhCDR2和vhCDR3结合人CD-3，并且VL的vlCDR1、vCDR2和vlCDR3结合人CD-3，但是在前药形式(例如未裂解的前药形式)中，VH和VL不能空间缔合来形成活性结合结构域，而是优选与伪Fv分子内配对。
如本文所述，受约束的Fv结构域可包含活性VH和活性VL(aVH和aVL)或无活性的VH和VL(iVH和iVL，在这种情况下，其是受约束的伪Fv结构域)或它们的组合。
如本领域技术人员将理解的，在受约束的Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
如本文所概述，对于形式1构建体，在诸如图5和图6中所示的那些的情况下，受约束的Fv结构域可包含使用可裂解的接头连接的VH和VL。在此实施方案中，受约束的Fv结构域具有结构(N-末端至C-末端)vhFR1-vhCDR1-vhFR2-vhCDR2-vhFR3-vhCDR3-vhFR4-CCL-vlFR1-vlCDR1-vlFR2-vlCDR2-vlFR3-vlCDR3-vlFR4。一般而言，受约束的Fv结构域含有活性VH和VL结构域(例如，当缔合时能够结合CD3的活性VH和VL结构域)，并且因此具有结构(N-末端至C-末端)vhFR1-avhCDR1-vhFR2-avhCDR2-vhFR3-avhCDR3-vhFR4-CCL-vlFR1-avlCDR1-vlFR2-avlCDR2-vlFR3-avlCDR3-vlFR4。
如本文所概述，对于形式2构建体，受约束的Fv结构域可包含使用不可裂解的接头连接的VH和VL。在此实施方案中，受约束的Fv结构域具有结构(N-末端至C-末端)vhFR1-vhCDR1-vhFR2-vhCDR2-vhFR3-vhCDR3-vhFR4-CNCL-vlFR1-vlCDR1-vlFR2-vlCDR2-vlFR3-vlCDR3-vlFR4。一般而言，受约束的Fv结构域含有活性VH和VL结构域(例如，当缔合时能够结合CD3的活性VH和VL结构域)，并且因此具有结构(N-末端至C-末端)vhFR1-avhCDR1-vhFR2-avhCDR2-vhFR3-avhCDR3-vhFR4-CNCL-vlFR1-avlCDR1-vlFR2-avlCDR2-vlFR3-avlCDR3-vlFR4。
在本发明中特别有用的是受约束的不可裂解的Fv结构域，所述受约束的不可裂解的Fv结构域具有：具有SEQ ID NO:61的aVH、具有SEQ ID NO:49的aVL和具有SEQ ID NO:74的结构域接头。
B.受约束的伪Fv结构域
本发明提供了受约束的伪Fv结构域，所述受约束的伪Fv结构域包含使用受约束的接头(如本文所概述，所述受约束的接头可以是可裂解的或不可裂解的接头)共价附接的无活性或伪iVH和iVL结构域。受约束的接头在不存在裂解的情况下阻止iVH与iVL之间的分子内缔合。因此，受约束的伪Fv结构域一般包含iVH和iVL，所述iVH和iVL具有允许iVH和iVL(当呈非受约束的形式时)缔合的框架区，但是所得的伪Fv结构域不结合至人蛋白质。iVH结构域可与aVL结构域组装，并且iVL结构域可与aVH结构域组装，但是所得结构不结合至CD3。
受约束的伪Fv结构域包含无活性的VH和VL(iVH和iVL)。
如本领域技术人员将理解的，在受约束的伪Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
如本文所概述，受约束的伪Fv结构域可包含使用不可裂解的接头(如形式1、2和4中所示)或用可裂解的接头(如形式3中所示)连接的iVH和iVL。
一般而言，受约束的Fv结构域含有惰性VH和VL结构域(例如，当缔合时能够结合CD3的惰性VH和VL结构域)，并且因此具有结构(N-末端至C-末端)vhFR1-ivlCDR1-vhFR2-ivlCDR2-vhFR3-ivlCDR3-vhFR4-CNCL-vlFR1-ivhCDR1-vlFR2-ivhCDR2-vlFR3-ivhCDR3-vlFR4。
在本发明中特别有用的是受约束的不可裂解的伪Fv结构域，所述受约束的不可裂解的伪Fv结构域具有：具有SEQ ID NO:65或SEQ ID NO:69的iVH、具有SEQ ID NO:53或SEQID NO:57的iVL，以及具有SEQ ID NO:74的结构域接头。
IX.本发明的形式
如本文所论述，本发明的前药构建体可采取许多不同形式，包括具有双TTA结合结构域的可裂解形式、具有双TTA结合结构域的不可裂解形式(这两者中的任一者均可具有相同的TTA结合结构域或不同的结合结构域)，以及具有单个靶向结构域的不可裂解的形式。
A.具有双重靶向能力的可裂解形式
本发明提供了图1中的“形式1”类型的非异构化可裂解形式。在此实施方案中，受约束的Fv结构域包含使用受约束的可裂解的接头连接的VH和VL结构域，并且受约束的伪Fv结构域使用受约束的不可裂解的接头。为了便于讨论，在本文中将这两个都称为“受约束的”，但是如上所论述以及如图36、图37和图38中所示，这些中的仅一个需要受约束，尽管一般来说，当这两个接头都受约束时，蛋白质具有更好的表达。
形式1(以及其他形式)中的所有构建体还具有被人肿瘤蛋白酶裂解的可裂解的接头(CL)。
本发明提供了前药蛋白，所述前药蛋白从N-末端至C-末端包含(sdABD-TTA1)-结构域接头-受约束的Fv结构域-结构域接头-(sdABD-TTA2)-CL-受约束的伪Fv结构域-结构域接头-sdABD-HSA。
如本领域技术人员将理解的，在受约束的Fv结构域或受约束的伪Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVH-CCL-iVL-结构域接头-sdABD-HSA。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVL-CCL-aVH-结构域接头-(sdABD-TTA2)-CL-iVL-CCL-iVH-结构域接头-sdABD-HSA。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVL-CCL-aVH-结构域接头-(sdABD-TTA2)-CL-iVH-CCL-iVL-结构域接头-sdABD-HSA。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-NCL-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH和iVL具有图5中所示的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至同一TTA，所述TTA可以是EGFR、EpCAM、FOLR1或B7H3，所述TTA的序列描绘于图5中。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至不同的TTA。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EGFR和EpCAM，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EGFR和FOLR1，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EGFR和B7H3，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EpCAM和FOLR1，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EpCAM和B7H3，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至B7H3和FOLR1，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药构建体包含sdABD(TTA1)-结构域接头-aVH-CCL-aVL-结构域接头-sdABD(TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD(1/2)。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至同一TTA，所述TTA可以是EGFR、FOLR1、B7H3或EpCAM，所述TTA的序列描绘于图5中，并且CCL和CL选自被MMP9或穿膜肽酶裂解的接头，并且sdABD(1/2)具有SEQ ID NO:45。
在形式1中，优选的结构域接头是SEQ ID NO:74(其还用作优选的受约束的不可裂解的接头)。
在形式1中，优选的构建体是Pro140和Pro140b。
B.不可裂解的形式
如图图2中所示，本发明提供了非异构化不可裂解的形式。在此实施方案中，应理解，“不可裂解的”仅适用于受约束的Fv结构域的连接键，因为前药构建体中存在活化裂解位点。在此实施方案中，受约束的Fv结构域包含使用受约束的不可裂解的接头连接的VH和VL结构域，并且受约束的伪Fv结构域使用受约束的不可裂解的接头。
如本领域技术人员将理解的，在受约束的Fv结构域或受约束的伪Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
本发明提供了前药蛋白，所述前药蛋白从N-末端至C-末端包含sdABD(TTA1)-结构域接头-受约束的Fv结构域-结构域接头-sdABD(TTA2)-可裂解的接头-受约束的伪Fv结构域-结构域接头-sdABD-HSA。
如本领域技术人员将理解的，在受约束的Fv结构域或受约束的伪Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVH-CNCL-iVL-结构域接头-sdABD-HSA。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVL-CNCL-aVH-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVL-CNCL-aVH-结构域接头-(sdABD-TTA2)-CL-iVH-CNCL-iVL-结构域接头-sdABD-HSA。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至同一TTA，所述TTA可以是EGFR、EpCAM、FOLR1或B7H3，所述TTA的序列描绘于图5中。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至不同的TTA。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EGFR和EpCAM，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EGFR和FOLR1，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EGFR和B7H3，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EpCAM和FOLR1，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至EpCAM和B7H3，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至FOLR1和B7H3，并且sdABD-TTA具有图5中的序列。
在一些实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA1)-结构域接头-aVH-CNCL-aVL-结构域接头-(sdABD-TTA2)-CL-iVL-CNCL-iVH-结构域接头-sdABD-HSA。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，该两个靶向结构域结合至同一TTA，所述TTA可以是EGFR、FOLR1、B7H3或EpCAM，所述TTA的序列描绘于图5中，并且CCL和CL选自被MMP9或穿膜肽酶裂解的接头，并且sdABD(1/2)具有SEQ ID NO:45。
在形式2中，优选的结构域接头是SEQ ID NO:74(其还用作优选的受约束的不可裂解的接头)。
在形式2中，特别有用的实施方案包括但不限于Pro186、Pro225、Pro226、Pro233、Pro311、Pro312、Pro313、Pro495、Pro246、Pro254、Pro255、Pro256、Pro420、Pro421、Pro432、Pro479、Pro480、Pro187、Pro221、Pro222、Pro223、Pro224、Pro393、Pro394、Pro395、Pro396、Pro429、Pro430以及Pro431。
C.单个TTA构建体
如图4中所示，“形式4”构建体也包括在本发明的组合物中，其类似于形式2构建体，但是没有第二TTA ABD。在此实施方案中，应理解，“不可裂解的”仅适用于受约束的Fv结构域的连接键，因为前药构建体中存在活化裂解位点。在此实施方案中，受约束的Fv结构域包含使用受约束的不可裂解的接头连接的VH和VL结构域，并且受约束的伪Fv结构域使用受约束的不可裂解的接头。
如本领域技术人员将理解的，在受约束的Fv结构域或受约束的伪Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
本发明提供了前药蛋白，所述前药蛋白从N-末端至C-末端包含sdABD(TTA)-结构域接头-受约束的Fv结构域-可裂解的接头-sdABD-HSA-受约束的伪Fv结构域。(注意，对于这种形式的所有构建体，sdABD-HSA一般都不具有His6标签，尽管可包含His6标签)。
如本领域技术人员将理解的，在受约束的Fv结构域或受约束的伪Fv结构域中，VH和VL的顺序可以是(N-末端至C-末端)VH-接头-VL或VL-接头-VH。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA)-结构域接头-aVH-CNCL-aVL-CL-(sdABD-HSA)-结构域接头-iVL-CNCL-iVH。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA)-结构域接头-aVH-CNCL-aVL-CL-(sdABD-HSA)-结构域接头-iVH-CNCL-iVL。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA)-结构域接头-aVL-CNCL-aVH-CL-(sdABD-HSA)-结构域接头-iVH-CNCL-iVL。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA)-结构域接头-aVL-CNCL-aVH-CL-(sdABD-HSA)-结构域接头-iVL-CNCL-iVH。
因此，在一个实施方案中，前药蛋白从N-末端至C-末端包含：(sdABD-TTA)-结构域接头-aVH-CNCL-aVL-CL-(sdABD-HSA)-结构域接头-iVL-CNCL-iVH。在此实施方案中，aVH、aVL、iVH、iVL具有图5中所示的序列。在此实施方案中，靶向结构域结合至TTA，所述TTA可以是EGFR、EpCAM、FOLR1或B7H3，所述TTA的序列描绘于图5中。
在形式4中，优选的结构域接头是SEQ ID NO:74(其还用作优选的受约束的不可裂解的接头)。
在形式4中，优选的sdABD-HSA是SEQ ID NO:45的sdABD-HSA。
D.两种蛋白质组合物
在一些实施方案中，本发明的组合物包含两个不同的分子，有时称为“半-COBRATM”或“半-构建体”，所述两个不同的分子在不存在裂解的情况下分子内缔合以形成伪Fv。在蛋白酶存在的情况下，裂解位点被裂解，从而释放惰性可变结构域，并且蛋白质对然后形成针对CD3的活性抗原结合结构域，如图3中所大体描绘的。
在半-构建体的设计中重要的是，裂解后活性可变结构域和sdABD-TTA保持在一起，以使得两个被裂解的部分通过肿瘤表面上的肿瘤抗原受体合在一起，并且然后可形成活性抗CD3结合结构域。
存在两种不同的通用形式3构建体，即，其中所述对中的每个成员具有单一sdABD-TTA的那些(3A)以及具有两个不同sdABD-TTA(各自针对不同的TTA)的那些(图3B)。
1.具有单个TTA结合结构域的半-COBRATM构建体(形式3A)
在一些实施方案中，第一半-COBRATM从N-末端至C-末端具有sdABD(TTA1)结构域接头-aVH-CL-iVL结构域接头-sdABD(1/2)，并且第二半-COBRATM具有sdABD(1/2)-结构域接头-iVH-CL-aVL-结构域接头-sdABD(TTA2)。在此实施方案中，aVH、aVL、iVH、iVL和sdABD(1/2)具有图5中所示的序列，并且sdABD-TTAa结合至人EGFR、EpCAM、FOLR1和/或B7H3，并且具有图5中描绘的序列。
2.具有双重TTA ABD的半-COBRATM构建体
在一些实施方案中，配对的前药构建体每个构建体可具有两个sdABD-TTA结合结构域，如图3B所示。在此实施方案中，所述对中的第一成员从N-末端至C-末端包含sdABD-TTA1-结构域接头-sdABD-TTA2-结构域接头-aVH-CL-iVL-结构域接头-sdABD(HAS)，并且第二成员从N-末端至C-末端包含sdABD-TTA1-结构域接头-sdABD-TTA2-aVL-CL-iVH-结构域接头-sdABD-HSA。
所述对中的每个成员上的两个sdABD-TTA不同，但通常两个成员(半-COBRATM)均具有相同的两个sdABD-TTA，例如均具有EGFR和FOLR1或者EGFR和B7H3，等等。
在一些实施方案中，该两个sdABD-TTA选自图5中所示的sdABD-TTA。
X.制备本发明的组合物的方法
如本领域技术人员通常所理解的并且在下文所概述的那样制备本发明的前药组合物。
本发明提供了编码本发明的前药组合物的核酸组合物。如本领域技术人员将理解的，所述核酸组合物将取决于一种或多种前药多肽的形式。因此，例如，当所述形式需要两个氨基酸序列时(如“形式3”构建体的情况)，可将两个核酸序列并入到一个或多个表达载体中用于表达。类似地，作为单个多肽的前药构建体(形式1、2和4)需要单个表达载体中的单一核酸来产生。
如本领域中已知的，可将编码本发明组分的核酸并入到如本领域中已知的并且取决于用于产生本发明前药组合物的宿主细胞的表达载体中。一般而言，核酸可操作地连接至任何数量的调控元件(启动子、复制起点、可选标记物、核糖体结合位点、诱导物等)。表达载体可以是染色体外载体或整合载体。
然后将本发明的核酸和/或表达载体转化到如本领域众所周知的任何数量的不同类型的宿主细胞中，所述宿主细胞包括哺乳动物、细菌、酵母、昆虫和/或真菌细胞，其中哺乳动物细胞(例如CHO细胞，293细胞)可用于许多实施方案中。
通过培养包含一种或多种如本领域所熟知的表达载体的宿主细胞来制备本发明的前药组合物。一旦产生，就进行传统的抗体纯化步骤，包括蛋白A亲和色谱分析步骤和/或离子交换色谱分析步骤。
XI.本发明的前药组合物的配制和施用
通过将具有所需纯度的前药(在形式1、2和4的情况下为单一蛋白质，而在形式3的情况下为两种蛋白质)与任选的药学上可接受的载体、赋形剂或稳定剂(如Remington’sPharmaceutical Sciences第16版,Osol,A.编辑[1980]中大体概述的)以冻干制剂或水溶液的形式混合来制备根据本发明使用的前药组合物的制剂用于储存。
本发明的前药组合物根据已知方法施用至受试者，所述已知方法诸如作为大丸剂静脉内施用或通过在一段时间内连续输注来静脉内施用。
本发明的前药组合物可用于治疗癌症。
XII.实施例
A.实施例1：Pro构建体的构建和纯化
转染
每种蛋白质(例如，对于形式1、2和4为单一蛋白质)或成对的构建体(形式3)是从单独表达载体(pcdna3.4衍生物)表达的。按照制造商的转染方案，将等量的编码一对半-眼镜蛇或单链构建体的质粒DNA混合并转染至Expi293细胞中。转染后5天，通过离心(6000rpmx 25’)和过滤(0.2uM过滤器)收获条件培养基。通过SDS-PAGE确认蛋白质表达。纯化构建体，并且最终的缓冲液组成是：25mM柠檬酸盐、75mM精氨酸、75mM NaCl、4％蔗糖，pH 7。将最终的制品储存在-80℃。
MMP9的活化
根据以下方案活化重组人(rh)MMP9。重组人MMP-9(R&D#911-MP-010)是0.44mg/ml(4.7uM)。在DMSO中以100mM的储备液浓度制备对氨基苯汞乙酸盐(APMA)(Sigma)。测定缓冲液是50mM Tris pH 7.5、10mM CaCl2、150mM NaCl、0.05％Brij-35。
-用测定缓冲液将rhMMP9稀释至约100ug/ml(25ul hMMP9+75uL测定缓冲液)
-添加来自100mM在DMSO中的储备液的对氨基苯汞乙酸盐(APMA)至终浓度1mM(1uL至100uL)
-在37'C下孵育24小时
-将MMP9稀释至10ng/ul(向100ul被活化的溶液中添加900ul测定缓冲液)
被活化的rhMMP9的浓度是约100nM。
用于TDCC测定的构建体的裂解
为了裂解该构建体，向100ul 1mg/ml浓度(10.5uM)的在配制缓冲液(25mM柠檬酸、75mM L-精氨酸、75mM NaCl、4％蔗糖)中的蛋白质样品中补充CaCl2至10mM。添加被活化的rhMMP9至浓度20-35nM。将样品在室温下孵育过夜(16-20小时)。使用SDS PAGE(10％-20％TG，TG运行缓冲液，200v，1小时)验证裂解的完成度。样品通常被98％裂解。
B.实施例2：T细胞依赖性细胞毒性(TDCC)测定
使萤火虫荧光素酶转导的HT-29细胞生长至大约80％汇合，并且用Versene(0.48mM在PBS中的EDTA–Ca-Mg)进行分裂。将细胞离心并重悬于TDCC培养基(5％的在含HEPES、GlutaMax、丙酮酸钠、非必需氨基酸和β-巯基乙醇的RPMI 1640中的热灭活FBS)中。将纯化的人全T细胞解冻，离心并重悬于TDCC培养基中。
将HT-29_Luc细胞和T细胞的共培养物添加至384孔细胞培养板中。然后将连续稀释的COBRA添加至共培养物中，并在37℃下孵育48小时。最后，将等体积的SteadyGlo荧光素酶测定试剂添加到板中并孵育20分钟。在Perkin Elmer Envision上以0.1秒/孔的曝光时间读板。记录总发光并在GraphPad Prism 7上分析数据。
C.实施例3：体内过继性T细胞转移功效模型的通用方案设计
这些方案被用于图中的许多实验中。将肿瘤细胞皮下(SC)植入到NSG(NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ)小鼠(The Jackson Laboratory，目录号005557)的右侧腹中并让其生长直至已建立的肿瘤的平均体积达到约200mm3。并行地，将人T细胞在T细胞培养基(X-VIVO 15[Lonza，目录号04-418Q]、5％人血清、1％青霉素/链霉素、0.01mM 2-巯基乙醇)中在G-Rex100M透气烧瓶(Wilson Wolf目录号81100S)中与来自T细胞活化/扩增试剂盒的MACSiBeads(Miltenyi目录号130-091-441)一起培养约10天，并且补充重组人IL-2蛋白。协调小鼠的肿瘤生长和人T细胞活化/扩增，以便在研究的第0天，基于肿瘤大小将小鼠随机分组(N＝6)；然后向每只小鼠静脉内注射(IV)2.5x106个培养的人T细胞，并且施用第一次剂量的COBRA或对照分子。以每隔3天给药的方式向小鼠给次7剂量(第0、3、6、9、12、15和18天)，且然后再追踪2-3周，直到肿瘤体积达到>2000mm3或研究终止。每隔3天测量肿瘤体积。
D.实施例4：EGFR/MMP9半-COBRA对Pro77和Pro53的体内活性。
将5x106个LoVo细胞或5x106个HT29细胞皮下植入到NSG(NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ)小鼠(The Jackson Laboratory，目录号005557)的右侧腹中，并且让其生长直至肿瘤被建立。并行地，将人T细胞在T细胞培养基(X-VIVO 15[Lonza，目录号04-418Q]、5％人血清、1％青霉素/链霉素、0.01mM 2-巯基乙醇)中在G-Rex100M透气烧瓶(Wilson Wolf目录号81100S)中与来自T细胞活化/扩增试剂盒的MACSiBeads(Miltenyi目录号130-091-441)一起培养10天，并且补充重组人IL-2蛋白。协调小鼠的肿瘤生长和人T细胞活化/扩增，以便在研究的第0天，基于肿瘤大小将小鼠随机分组(N＝6)；然后向每只小鼠静脉内注射(IV)2.5x106个培养的人T细胞，并且施用第一次剂量的COBRA或对照分子。以每隔3天给药的方式向小鼠给予7次剂量(第0、3、6、9、12、15和18天)，且然后追踪直到肿瘤体积达到>2000mm3或研究终止。各组接受0.2mg/kg(mpk)的抗EGFR x CD3阳性对照Pro51双特异性抗体(bsAb)、0.5mpk的阴性对照抗鸡卵溶菌酶(HEL)x CD3 bsAb Pro98、0.5mpk的含有MMP9可裂解接头的抗EGFR半-COBRA对Pro77和Pro53中的每一种，或0.5mpk的含有不可裂解的(NCL)接头的抗EGFR半-COBRA对Pro74和Pro72中的每一种。每隔3天测量肿瘤体积。
E.实施例5：EGFR/MMP9 COBRA Pro140的体内活性。
将5x106个LoVo细胞或5x106个HT29细胞皮下植入到NSG(NOD.Cg-PrkdcscidIl2rgtm1Wjl/SzJ)小鼠(The Jackson Laboratory，目录号005557)的右侧腹中，并且让其生长直至肿瘤被建立。并行地，将人T细胞在T细胞培养基(X-VIVO 15[Lonza，目录号04-418Q]、5％人血清、1％青霉素/链霉素、0.01mM 2-巯基乙醇)中在G-Rex100M透气烧瓶(Wilson Wolf目录号81100S)中与来自T细胞活化/扩增试剂盒的MACSiBeads(Miltenyi目录号130-091-441)一起培养10天，并且补充重组人IL-2蛋白。协调小鼠的肿瘤生长和人T细胞活化/扩增，以便在研究的第0天，基于肿瘤大小将小鼠随机分组(N＝6)；然后向每只小鼠静脉内注射(IV)2.5x106个培养的人T细胞，并且施用第一次剂量的COBRA或对照分子。以每隔3天给药的方式向小鼠给予7次剂量(第0、3、6、9、12、15和18天)，且然后追踪直到肿瘤体积达到>2000mm3或研究终止。各组接受0.2mpk的抗EGFR x CD3阳性对照Pro51双特异性抗体(bsAb)、0.5mpk的阴性对照抗鸡卵溶菌酶(HEL)x CD3 bsAb Pro98，或0.5mpk的含有MMP9可裂解接头的抗EGFR COBRA Pro140。每隔3天测量肿瘤体积。
F.实施例6：EGFR/MMP9 COBRA Pro186的体内活性。
将5x106个HT29细胞皮下植入到NSG(NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ)小鼠(The Jackson Laboratory，目录号005557)的右侧腹中，并且让其生长直至肿瘤被建立。并行地，将人T细胞在T细胞培养基(X-VIVO 15[Lonza，目录号04-418Q]、5％人血清、1％青霉素/链霉素、0.01mM 2-巯基乙醇)中在G-Rex100M透气烧瓶(Wilson Wolf目录号81100S)中与来自T细胞活化/扩增试剂盒的MACSiBeads(Miltenyi目录号130-091-441)一起培养10天，并且补充重组人IL-2蛋白。协调小鼠的肿瘤生长和人T细胞活化/扩增，以便在研究的第0天，基于肿瘤大小将小鼠随机分组(N＝6)；然后向每只小鼠静脉内注射(IV)2.5x106个培养的人T细胞，并且施用第一次剂量的COBRA或对照分子。以每隔3天给药的方式向小鼠给予7次剂量(第0、3、6、9、12、15和18天)，且然后追踪直到肿瘤体积达到>2000mm3或研究终止。各组接受0.1mg/kg(mpk)的抗EGFR x CD3阳性对照Pro51双特异性抗体(bsAb)、0.3mpk的含不可裂解的(NCL)对照接头的抗EGFR COBRA Pro214、0.1或0.3mpk的含MMP9可裂解的接头的抗EGFR COBRA Pro140，或0.1或0.3mpk的含MMP9可裂解的接头的抗EGFR COBRA Pro186。每隔3天测量肿瘤体积。
G.实施例：抗EGFR序列的成功人源化
结果如下所示。
Figure BDA0002481085060000611
Figure BDA0002481085060000621
这些结果表明，EGFR结合结构域的人源化是成功的，并且当分子上有两个结合位点时，对靶EGFR存在强亲合力。
实施例：EpCAM sdABD的成功人源化
结果如下所示。
Figure BDA0002481085060000622
这些结果表明，EpCAM结合结构域的人源化是成功的。
序列表
<110> 马弗里克治疗公司
<120> 受约束的条件性活化的结合蛋白
<130> 118459-5005
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<151> 2017-09-08
<150> 62/586,627
<151> 2017-11-15
<150> 62/587,318
<151> 2017-11-16
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<211> 113
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-靶向sdAbs -α-FOLR1
h59.3
<400> 21
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser
<210> 22
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -靶向sdAbs -α-FOLR1 h59.3
<400> 22
Gly Asn Thr Phe Ser Ile Ser Ala Met Gly
1 5 10
<210> 23
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -靶向sdAbs -α-FOLR1 h59.3
<400> 23
Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 24
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -靶向sdAbs -α-FOLR1 h59.3
<400> 24
Tyr Gly Ile Asp Tyr
1 5
<210> 25
<211> 117
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-靶向sdAbs -α-FOLR1
h22-4
<400> 25
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser
115
<210> 26
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -靶向sdAbs -α-FOLR1 h22-4
<400> 26
Gly Thr Thr Phe Ser Arg Asp Val Met Gly
1 5 10
<210> 27
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -靶向sdAbs -α-FOLR1 h22-4
<400> 27
Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 28
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -靶向sdAbs -α-FOLR1 h22-4
<400> 28
Asn Thr Ala Thr Trp Gly Arg Val Phe
1 5
<210> 29
<211> 124
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-靶向sdAbs -α-B7H3
hF7
<400> 29
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 30
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -靶向sdAbs -α-B7H3 hF7
<400> 30
Arg Arg Thr Phe His Thr Tyr His Met Gly
1 5 10
<210> 31
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -靶向sdAbs -α-B7H3 hF7
<400> 31
Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 32
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -靶向sdAbs -α-B7H3 hF7
<400> 32
Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr
1 5 10 15
<210> 33
<211> 122
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-靶向sdAbs -α-B7H3
hF12
<400> 33
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 34
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -靶向sdAbs -α-B7H3 hF12
<400> 34
Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala
1 5 10
<210> 35
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -靶向sdAbs -α-B7H3 hF12
<400> 35
Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys
1 5 10 15
Gly
<210> 36
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -靶向sdAbs -α-B7H3 hF12
<400> 36
Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr
1 5 10
<210> 37
<211> 122
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-靶向sdAbs -α-EpCAM
h13
<400> 37
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 38
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -靶向sdAbs -α-EpCAM h13
<400> 38
Gly Thr Gly Ser Ile Phe Ser Ile Asn Leu Met Gly
1 5 10
<210> 39
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -靶向sdAbs -α-EpCAM h13
<400> 39
Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 40
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -靶向sdAbs -α-EpCAM h13
<400> 40
Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr
1 5 10
<210> 41
<211> 122
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-靶向sdAbs -α-EpCAM
h23
<400> 41
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 42
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -靶向sdAbs -α-EpCAM h23
<400> 42
Gly Ser Phe Ser Ala Leu Trp Ala Met Arg
1 5 10
<210> 43
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -靶向sdAbs -α-EpCAM h23
<400> 43
Ser Ser Arg Gly Gly Thr Thr Ser Tyr Ala Asp Ser Val Lys Gly
1 5 10 15
<210> 44
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -靶向sdAbs -α-EpCAM h23
<400> 44
Ile Asp Gly His Leu Ala Tyr
1 5
<210> 45
<211> 115
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-HSA半衰期延长
结构域
<400> 45
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
20 25 30
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser
115
<210> 46
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR1 -α-HSA半衰期延长结构域
<400> 46
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser
1 5 10
<210> 47
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR2 -α-HSA半衰期延长结构域
<400> 47
Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys
1 5 10 15
Gly
<210> 48
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成sdCDR3 -α-HSA半衰期延长结构域
<400> 48
Gly Gly Ser Leu Ser Val
1 5
<210> 49
<211> 109
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-CD3 scFv 结构域 -
α-CD3V(L)
<400> 49
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 50
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成aVLCDR1 -α CD3 scFV 结构域 -α-CD3 V(L)
<400> 50
Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
1 5 10
<210> 51
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成aVLsdCDR2 -α CD3 scFV 结构域 -α-CD3 V(L)
<400> 51
Gly Thr Lys Phe Leu Val Pro
1 5
<210> 52
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成aVLsdCDR3 -α CD3 scFV 结构域 -α-CD3 V(L)
<400> 52
Thr Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<210> 53
<211> 110
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-CD3 scFv 结构域 -
α-CD3V(Li)
<400> 53
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg
50 55 60
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
65 70 75 80
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser
85 90 95
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105 110
<210> 54
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVLCDR1 -α CD3 scFV 结构域 -α-CD3 V(Li)
<400> 54
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
1 5 10
<210> 55
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVLsdCDR2 -α CD3 scFV 结构域 -α-CD3 V(Li)
<400> 55
Asp Tyr Lys Asp Asp Asp Asp Lys
1 5
<210> 56
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVLsdCDR3 -α CD3 scFV 结构域 -α-CD3 V(Li)
<400> 56
Val Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<210> 57
<211> 109
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-CD3 scFv 结构域 -
α-CD3V(Li2)
<400> 57
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
1 5 10 15
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
20 25 30
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
35 40 45
Leu Ile Gly Gly Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe
50 55 60
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
65 70 75 80
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
85 90 95
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 58
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVLCDR1 -α CD3 scFV 结构域 -α-CD3 V(Li2)
<400> 58
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
1 5 10
<210> 59
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVLCDR2 -α CD3 scFV 结构域 -α-CD3 V(Li2)
<400> 59
Gly Thr Lys Asp Asp Ala Pro
1 5
<210> 60
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVLCDR3 -α CD3 scFV 结构域 -α-CD3 V(Li2)
<400> 60
Val Leu Trp Tyr Ser Asn Arg Trp Val
1 5
<210> 61
<211> 125
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-CD3 scFv 结构域 -
α-CD3V(H)
<400> 61
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
20 25 30
Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
50 55 60
Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 62
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成aVHCDR1 -α CD3 scFV 结构域 -α-CD3 V(H)
<400> 62
Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
1 5 10
<210> 63
<211> 19
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成aVHsdCDR2 -α CD3 scFV 结构域 -α-CD3 V(H)
<400> 63
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln
1 5 10 15
Val Lys Asp
<210> 64
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成aVHsdCDR3 -α CD3 scFV 结构域 -α-CD3 V(H)
<400> 64
His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
1 5 10
<210> 65
<211> 126
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-CD3 scFv 结构域 -
α-CD3V(Hi)
<400> 65
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
50 55 60
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
65 70 75 80
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
85 90 95
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
100 105 110
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 66
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVHsdCDR1 -α CD3 scFV 结构域 -α-CD3 V(Hi)
<400> 66
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
1 5 10
<210> 67
<211> 20
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVHsdCDR2 -α CD3 scFV 结构域 -α-CD3 V(Hi)
<400> 67
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
1 5 10 15
Ser Val Lys Asp
20
<210> 68
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVHsdCDR3 -α CD3 scFV 结构域 -α-CD3 V(Hi)
<400> 68
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
1 5 10
<210> 69
<211> 125
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-CD3 scFv 结构域 -
α-CD3V(Hi2)
<400> 69
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys His
20 25 30
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp
50 55 60
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
65 70 75 80
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
85 90 95
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
100 105 110
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120 125
<210> 70
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVHsdCDR1 -α CD3 scFV 结构域 -α-CD3 V(Hi2)
<400> 70
Gly Phe Thr Phe Asn Lys His Ala Met Asn
1 5 10
<210> 71
<211> 19
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVHsdCDR2 -α CD3 scFV 结构域 -α-CD3 V(Hi2)
<400> 71
Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp Ser
1 5 10 15
Val Lys Asp
<210> 72
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成iVHsdCDR3 -α CD3 scFV 结构域 -α-CD3 V(Hi2)
<400> 72
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
1 5 10
<210> 73
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成接头 -α-CD3 scFV - 正常，不可裂解的
<400> 73
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 74
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成接头 -α-CD3 scFV -受约束的
<400> 74
Gly Gly Gly Ser Gly Gly Gly Ser
1 5
<210> 75
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - MMP 2/9
<400> 75
Gly Pro Ala Gly Met Lys Gly Leu
1 5
<210> 76
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - MMP 2/9
<400> 76
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser
1 5 10 15
<210> 77
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - MMP 2/9
<400> 77
Ser Gly Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Gly
1 5 10 15
Ser
<210> 78
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - Meprin A/B
<400> 78
Gly Gly Gly Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser
1 5 10 15
<210> 79
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - Meprin A/B
<400> 79
Lys Lys Leu Ala Asp Glu Pro Glu
1 5
<210> 80
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - Meprin A/B (变体，高
效)
<400> 80
Gly Gly Gly Lys Phe Leu Ala Asp Glu Pro Glu Gly Gly
1 5 10
<210> 81
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 组织蛋白酶S、K、L
<400> 81
Ser Gly Gly Gly Ala Arg Leu Gln Ser Ala Ala Pro Gly Gly Gly Ser
1 5 10 15
<210> 82
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 组织蛋白酶S、K、L
<400> 82
Ala Arg Leu Gln Ser Ala Ala Pro
1 5
<210> 83
<211> 18
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - Meprin/颗粒酶B
<400> 83
Ser Gly Gly Gly Gly Val Tyr Ala Asp Ser Leu Glu Asp Gly Gly Gly
1 5 10 15
Gly Ser
<210> 84
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - Meprin/颗粒酶B
<400> 84
Gly Val Tyr Ala Asp Ser Leu Glu Asp Gly
1 5 10
<210> 85
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 蛋白裂解酶/uPA (MS)
<400> 85
Gly Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Gly Gly Ser
1 5 10 15
<210> 86
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 蛋白裂解酶/uPA (MS)
<400> 86
Gly Leu Ser Gly Arg Ser Asp Asn His Gly
1 5 10
<210> 87
<211> 17
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 蛋白裂解酶 (MV)
<400> 87
Ser Gly Gly Gly Ser Phe Thr Arg Gln Ala Arg Val Val Gly Gly Gly
1 5 10 15
Ser
<210> 88
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 蛋白裂解酶 (MV)
<400> 88
Ser Phe Thr Arg Gln Ala Arg Val Val
1 5
<210> 89
<211> 14
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 组织蛋白酶S/MMP9/Meprin A
<400> 89
Ala Arg Leu Gln Ser Ala Ala Pro Ala Gly Leu Lys Gly Ala
1 5 10
<210> 90
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - MMP9 (变体，高效)
<400> 90
Gly Gly Pro Gly Pro Ala Gly Met His Gly Leu Pro Gly
1 5 10
<210> 91
<211> 13
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - MMP9 (变体，低效)
<400> 91
Gly Gly Pro Gly Pro Ala Gly Met Glu Gly Leu Pro Gly
1 5 10
<210> 92
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 凝血酶1
<400> 92
Gly Gly Gly Gly Leu Val Pro Arg Gly Ser Leu Gly Gly Gly Gly Ser
1 5 10 15
<210> 93
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 凝血酶2
<400> 93
Ser Ser Gly Gly Gly Met Pro Arg Ser Phe Arg Gly Gly Gly Ser
1 5 10 15
<210> 94
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - 肠激酶/Flag
<400> 94
Gly Gly Gly Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Gly Gly Ser
1 5 10 15
<210> 95
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - KLK7-6
<400> 95
Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala Gly Arg Gly Gly Gly Ser
1 5 10 15
<210> 96
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - KLK7-13
<400> 96
Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala Gly Gly Gly Ser Gly Gly
1 5 10 15
<210> 97
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - KLK7-11
<400> 97
Ser Gly Gly Gly Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly
1 5 10 15
<210> 98
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - KLK7-10
<400> 98
Ser Gly Gly Gly Gln Asn Thr Trp Ser Ala Gly Lys Gly Gly Gly Ser
1 5 10 15
<210> 99
<211> 16
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - uPA
<400> 99
Gly Gly Gly Ser His Thr Gly Arg Ser Ala Tyr Phe Gly Gly Gly Ser
1 5 10 15
<210> 100
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP7
<400> 100
Lys Arg Ala Leu Gly Leu Pro Gly
1 5
<210> 101
<211> 24
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP7
<220>
<221> misc_feature
<222> (1)..(8)
<223> X可以是Asp或Glu
<220>
<221> misc_feature
<222> (17)..(24)
<223> X可以是Asp或Arg
<400> 101
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa Arg Pro Leu Ala Leu Trp Arg Ser
1 5 10 15
Xaa Xaa Xaa Xaa Xaa Xaa Xaa Xaa
20
<210> 102
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP9
<400> 102
Pro Arg Ser Thr Leu Ile Ser Thr
1 5
<210> 103
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP9
<400> 103
Leu Glu Ala Thr Ala
1 5
<210> 104
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP11
<400> 104
Gly Gly Ala Ala Asn Leu Val Arg Gly Gly
1 5 10
<210> 105
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP14
<400> 105
Ser Gly Arg Ile Gly Phe Leu Arg Thr Ala
1 5 10
<210> 106
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP
<400> 106
Pro Leu Gly Leu Ala Gly
1 5
<210> 107
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP
<220>
<221> misc_feature
<222> (6)..(6)
<223> Xaa可以是任何天然存在的氨基酸
<400> 107
Pro Leu Gly Leu Ala Xaa
1 5
<210> 108
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP
<220>
<221> misc_feature
<222> (5)..(5)
<223> X可以是Met或Glu
<400> 108
Pro Leu Gly Cys Xaa Ala Gly
1 5
<210> 109
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP
<400> 109
Glu Ser Pro Ala Tyr Tyr Thr Ala
1 5
<210> 110
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP
<400> 110
Arg Leu Gln Leu Lys Leu
1 5
<210> 111
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP
<400> 111
Arg Leu Gln Leu Lys Ala Cys
1 5
<210> 112
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - MMP2、MMP9、MMP14
<220>
<221> misc_feature
<222> (1)..(3)
<223> X可以是Cys或Ile或Thr
<220>
<221> misc_feature
<222> (5)..(5)
<223> X可以是His或Orn或Phe
<400> 112
Glu Pro Xaa Gly Xaa Tyr Leu
1 5
<210> 113
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 尿激酶纤溶酶原
活化因子(upa)
<400> 113
Ser Gly Arg Ser Ala
1 5
<210> 114
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 尿激酶纤溶酶原
活化因子(upa)
<400> 114
Asp Ala Phe Lys
1
<210> 115
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 尿激酶纤溶酶原
活化因子(upa)
<400> 115
Gly Gly Gly Arg Arg
1 5
<210> 116
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 溶酶体酶
<400> 116
Gly Phe Leu Gly
1
<210> 117
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 溶酶体酶
<400> 117
Ala Leu Ala Leu
1
<210> 118
<211> 2
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 溶酶体酶
<400> 118
Phe Lys
1
<210> 119
<211> 3
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 组织蛋白酶 B
<400> 119
Asn Leu Leu
1
<210> 120
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 组织蛋白酶 D
<220>
<221> misc_feature
<222> (4)..(4)
<223> X可以是Glu或Thr
<400> 120
Pro Ile Cys Xaa Phe Phe
1 5
<210> 121
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 组织蛋白酶 K
<400> 121
Gly Gly Pro Arg Gly Leu Pro Gly
1 5
<210> 122
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 前列腺特异性抗原
<400> 122
His Ser Ser Lys Leu Gln
1 5
<210> 123
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 前列腺特异性抗原
<400> 123
His Ser Ser Lys Leu Gln Leu
1 5
<210> 124
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 前列腺特异性抗原
<400> 124
His Ser Ser Lys Leu Gln Glu Asp Ala
1 5
<210> 125
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 单纯疱疹病毒蛋白酶
<400> 125
Leu Val Leu Ala Ser Ser Ser Phe Gly Tyr
1 5 10
<210> 126
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - Hiv蛋白酶
<400> 126
Gly Val Ser Gln Asn Tyr Pro Ile Val Gly
1 5 10
<210> 127
<211> 10
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - Cmv蛋白酶
<400> 127
Gly Val Val Gln Ala Ser Cys Arg Leu Ala
1 5 10
<210> 128
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 凝血酶
<220>
<221> misc_feature
<222> (2)..(2)
<223> X可以是Pro或Ile或Pro
<400> 128
Phe Xaa Arg Ser
1
<210> 129
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 凝血酶
<400> 129
Asp Pro Arg Ser Phe Leu
1 5
<210> 130
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 凝血酶
<400> 130
Pro Pro Arg Ser Phe Leu
1 5
<210> 131
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 半胱天冬酶-3
<400> 131
Asp Glu Val Asp
1
<210> 132
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 半胱天冬酶-3
<400> 132
Asp Glu Val Asp Pro
1 5
<210> 133
<211> 8
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 半胱天冬酶-3
<400> 133
Lys Gly Ser Gly Asp Val Glu Gly
1 5
<210> 134
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 白介素1-β转化
酶
<400> 134
Gly Trp Glu His Asp Gly
1 5
<210> 135
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 肠激酶
<400> 135
Glu Asp Asp Asp Asp Lys Ala
1 5
<210> 136
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - Fap
<400> 136
Lys Gln Glu Gln Asn Pro Gly Ser Thr
1 5
<210> 137
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 激肽释放酶2
<400> 137
Gly Lys Ala Phe Arg Arg
1 5
<210> 138
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 纤溶酶
<400> 138
Asp Ala Phe Lys
1
<210> 139
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 纤溶酶
<400> 139
Asp Val Leu Lys
1
<210> 140
<211> 4
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - 纤溶酶
<400> 140
Asp Ala Phe Lys
1
<210> 141
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成蛋白酶裂解位点 - Top
<400> 141
Ala Leu Leu Leu Ala Leu Leu
1 5
<210> 142
<211> 121
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成抗原结合结构域-α-HSA半衰期延长
结构域
<400> 142
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
20 25 30
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
100 105 110
Val Ser Ser His His His His His His
115 120
<210> 143
<211> 889
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro140形式1
<400> 143
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser
885
<210> 144
<211> 890
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro140b形式1
<400> 144
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Lys Lys Leu Ala Asp Glu Pro Glu Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys
500 505 510
Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 145
<211> 889
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro186形式2
<400> 145
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser
885
<210> 146
<211> 890
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro187形式2
<400> 146
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys
500 505 510
Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 147
<211> 895
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro225 (FL aB7H3 hF7 MMP9 接头)形式2
<400> 147
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val
420 425 430
Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 148
<211> 891
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro226 (FL aB7H3 hF12 MMP9 接头)形式2
<400> 148
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu
370 375 380
Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
385 390 395 400
Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala Ile Asn
420 425 430
Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly
465 470 475 480
Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr
485 490 495
Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys
500 505 510
Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
515 520 525
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
530 535 540
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
545 550 555 560
Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys
565 570 575
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
580 585 590
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
595 600 605
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
610 615 620
Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
625 630 635 640
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
645 650 655
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val
660 665 670
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
675 680 685
Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp
690 695 700
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
705 710 715 720
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
725 730 735
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
740 745 750
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
755 760 765
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
770 775 780
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
785 790 795 800
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
805 810 815
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
820 825 830
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
835 840 845
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
850 855 860
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
865 870 875 880
Val Thr Val Ser Ser His His His His His His
885 890
<210> 149
<211> 895
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro233 (人源化Pro186)形式2
<400> 149
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 150
<211> 875
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro311 (FL aFOLR1 h77.2 MMP9 接头)形式
2
<400> 150
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu
405 410 415
Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala
420 425 430
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
435 440 445
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
450 455 460
Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr
465 470 475 480
Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys
485 490 495
Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
500 505 510
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
515 520 525
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
530 535 540
Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys
545 550 555 560
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
565 570 575
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
580 585 590
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
595 600 605
Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
610 615 620
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
625 630 635 640
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val
645 650 655
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
660 665 670
Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp
675 680 685
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
690 695 700
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
705 710 715 720
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
725 730 735
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
740 745 750
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
755 760 765
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
770 775 780
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
785 790 795 800
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
805 810 815
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
820 825 830
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
835 840 845
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
850 855 860
Val Thr Val Ser Ser His His His His His His
865 870 875
<210> 151
<211> 873
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro312 (FL aFOLR1 h59.3 MMP9 接头)
<400> 151
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
355 360 365
Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
370 375 380
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe
385 390 395 400
Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg
405 410 415
Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp
420 425 430
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
435 440 445
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
450 455 460
Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val
465 470 475 480
Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu
485 490 495
Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser
500 505 510
Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val
515 520 525
Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala
530 535 540
Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr
545 550 555 560
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
565 570 575
Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu
580 585 590
Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
595 600 605
Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
610 615 620
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
625 630 635 640
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln
645 650 655
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
660 665 670
Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe
675 680 685
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
690 695 700
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly
705 710 715 720
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
725 730 735
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser
740 745 750
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
755 760 765
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
770 775 780
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
785 790 795 800
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
805 810 815
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
820 825 830
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
835 840 845
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
850 855 860
Val Ser Ser His His His His His His
865 870
<210> 152
<211> 881
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro313 (FL aFOLR1 h22.4 MMP9 接头)形式
2
<400> 152
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro
485 490 495
Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr
500 505 510
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
515 520 525
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
530 535 540
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
545 550 555 560
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
565 570 575
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
580 585 590
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
595 600 605
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
610 615 620
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
625 630 635 640
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
645 650 655
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
660 665 670
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
675 680 685
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
690 695 700
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
705 710 715 720
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
725 730 735
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
740 745 750
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
755 760 765
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
770 775 780
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
785 790 795 800
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
805 810 815
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
820 825 830
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
835 840 845
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
850 855 860
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
865 870 875 880
His
<210> 153
<211> 898
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro246 (具有MMP9 接头的FL haEGFR1/haEGFR2异质
COBRA)
<400> 153
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr
100 105 110
Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
115 120 125
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
130 135 140
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
145 150 155 160
Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro
165 170 175
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
180 185 190
Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser
195 200 205
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
210 215 220
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly
225 230 235 240
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
245 250 255
Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
260 265 270
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
275 280 285
Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
290 295 300
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
305 310 315 320
Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
325 330 335
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
340 345 350
Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe
355 360 365
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
370 375 380
Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly
385 390 395 400
Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser
405 410 415
Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe
420 425 430
Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser
435 440 445
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu
450 455 460
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr
465 470 475 480
Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr
485 490 495
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly
500 505 510
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val
515 520 525
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
530 535 540
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
545 550 555 560
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
565 570 575
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
580 585 590
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
595 600 605
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
610 615 620
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
645 650 655
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
660 665 670
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
675 680 685
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
690 695 700
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
705 710 715 720
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
725 730 735
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
740 745 750
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
755 760 765
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
770 775 780
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
785 790 795 800
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
805 810 815
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
820 825 830
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
835 840 845
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
850 855 860
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
865 870 875 880
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His
885 890 895
His His
<210> 154
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro256 (FL haEpCAM VIB13/haEGFR1
异质COBRA MMP9 接头)
<400> 154
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Lys Leu
370 375 380
Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu Thr Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser
420 425 430
Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ala Ala
465 470 475 480
Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
565 570 575
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
625 630 635 640
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
645 650 655
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
660 665 670
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
675 680 685
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 155
<211> 885
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro420 (FL aFOLR1 h77.2/haEGFR1
异质COBRA MMP9 接头)
<400> 155
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
355 360 365
Gly Gly Gly Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val
370 375 380
Arg Pro Gly Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr
385 390 395 400
Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu
405 410 415
Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr
420 425 430
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
435 440 445
Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala
450 455 460
Leu Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu
465 470 475 480
Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490 495
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
500 505 510
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
515 520 525
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
530 535 540
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
545 550 555 560
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
565 570 575
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
580 585 590
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
595 600 605
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
610 615 620
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
625 630 635 640
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
645 650 655
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
660 665 670
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
675 680 685
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
690 695 700
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
705 710 715 720
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
725 730 735
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
740 745 750
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
755 760 765
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
770 775 780
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
785 790 795 800
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
805 810 815
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
820 825 830
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
835 840 845
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
850 855 860
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
865 870 875 880
His His His His His
885
<210> 156
<211> 885
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro421 (FL haEGFR1/aFOLR1 h77.2
异质COBRA MMP9 接头)
<400> 156
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser Val Met
405 410 415
Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val Ala Ile
420 425 430
Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys Gly Arg
435 440 445
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met
450 455 460
Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn Arg Asn
465 470 475 480
Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490 495
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
500 505 510
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
515 520 525
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
530 535 540
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
545 550 555 560
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
565 570 575
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
580 585 590
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
595 600 605
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
610 615 620
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
625 630 635 640
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
645 650 655
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
660 665 670
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
675 680 685
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
690 695 700
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
705 710 715 720
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
725 730 735
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
740 745 750
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
755 760 765
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
770 775 780
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
785 790 795 800
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
805 810 815
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
820 825 830
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
835 840 845
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
850 855 860
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
865 870 875 880
His His His His His
885
<210> 157
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro393 (Pro186 S9 接头)
<400> 157
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Ala Arg Leu Gln Ser
500 505 510
Ala Ala Pro Ala Gly Leu Lys Gly Ala Gly Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 158
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro394 (Pro186 ST14(MV) 接头)
<400> 158
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr
500 505 510
Arg Gln Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 159
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro395 (Pro186 CathS 接头)
<400> 159
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg
500 505 510
Leu Gln Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 160
<211> 897
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro396 (Pro186 MMP9v 接头)
<400> 160
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Ser Gly Gly Pro Gly
500 505 510
Pro Ala Gly Met His Gly Leu Pro Gly Gly Ser Gln Thr Val Val Thr
515 520 525
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
530 535 540
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
545 550 555 560
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
565 570 575
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
580 585 590
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
595 600 605
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
610 615 620
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
645 650 655
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
660 665 670
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
675 680 685
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
690 695 700
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
705 710 715 720
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
725 730 735
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
740 745 750
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
755 760 765
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
770 775 780
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
785 790 795 800
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
805 810 815
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
820 825 830
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
835 840 845
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
850 855 860
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
865 870 875 880
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
885 890 895
His
<210> 161
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro429 (Pro186 Meprin/颗粒酶B接头)
<400> 161
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Val Tyr
500 505 510
Ala Asp Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 162
<211> 895
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro430 (Pro186 MMP9-2 接头)
<400> 162
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Leu Lys Gly Ala Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 163
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro431 (Pro186 ST14(MS) 接头)
<400> 163
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser
500 505 510
Gly Arg Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 164
<211> 763
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro258 (具有单个aEGFR 结构域和中心aHSA 结构域的Pro186)
<400> 164
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala Gly Met Lys
370 375 380
Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
385 390 395 400
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
405 410 415
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
420 425 430
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
435 440 445
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
450 455 460
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
465 470 475 480
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
500 505 510
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
515 520 525
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser
530 535 540
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
545 550 555 560
Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala
565 570 575
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
580 585 590
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr
595 600 605
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
610 615 620
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
625 630 635 640
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
645 650 655
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
660 665 670
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
675 680 685
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
690 695 700
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
705 710 715 720
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
725 730 735
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
740 745 750
Val Thr Val Ser Ser His His His His His His
755 760
<210> 165
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro221 - 可裂解的接头变体
<400> 165
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn
500 505 510
Pro Tyr Ser Ala Gly Arg Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 166
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro222 - 可裂解的接头变体
<400> 166
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn
500 505 510
Pro Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 167
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro223 - 可裂解的接头变体
<400> 167
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Arg Asn
500 505 510
Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 168
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro224- 可裂解的接头变体
<400> 168
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn
500 505 510
Thr Trp Ser Ala Gly Lys Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 169
<211> 898
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro254- 异质形式2
<400> 169
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Ala Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Val Ala
420 425 430
Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr
485 490 495
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly
500 505 510
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val
515 520 525
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
530 535 540
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
545 550 555 560
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
565 570 575
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
580 585 590
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
595 600 605
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
610 615 620
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
645 650 655
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
660 665 670
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
675 680 685
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
690 695 700
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
705 710 715 720
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
725 730 735
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
740 745 750
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
755 760 765
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
770 775 780
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
785 790 795 800
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
805 810 815
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
820 825 830
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
835 840 845
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
850 855 860
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
865 870 875 880
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His
885 890 895
His His
<210> 170
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro255- 异质形式2
<400> 170
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
565 570 575
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
625 630 635 640
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
645 650 655
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
660 665 670
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
675 680 685
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 171
<211> 902
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro262
<400> 171
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
275 280 285
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
290 295 300
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
305 310 315 320
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
325 330 335
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
340 345 350
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
355 360 365
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
370 375 380
Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser
385 390 395 400
Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg
405 410 415
Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys
420 425 430
Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly
435 440 445
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
450 455 460
Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr
465 470 475 480
Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr
485 490 495
Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser
500 505 510
Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser
515 520 525
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
530 535 540
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
545 550 555 560
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
565 570 575
Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg
580 585 590
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
595 600 605
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser
610 615 620
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
770 775 780
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg
785 790 795 800
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser
805 810 815
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile
820 825 830
Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg
835 840 845
Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met
850 855 860
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly
865 870 875 880
Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890 895
His His His His His His
900
<210> 172
<211> 766
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro356 -形式4
<400> 172
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr
100 105 110
Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
115 120 125
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
130 135 140
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
145 150 155 160
Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro
165 170 175
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
180 185 190
Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser
195 200 205
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
210 215 220
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly
225 230 235 240
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
245 250 255
Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
260 265 270
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
275 280 285
Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
290 295 300
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
305 310 315 320
Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
325 330 335
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
340 345 350
Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe
355 360 365
Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala
370 375 380
Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly
385 390 395 400
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
405 410 415
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
420 425 430
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
435 440 445
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
450 455 460
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
465 470 475 480
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
485 490 495
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
500 505 510
Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
515 520 525
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
530 535 540
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln
545 550 555 560
Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly
565 570 575
Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
580 585 590
Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val
595 600 605
Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
610 615 620
Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
625 630 635 640
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
645 650 655
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg
660 665 670
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
675 680 685
Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg
690 695 700
Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met
705 710 715 720
Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His
725 730 735
Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln
740 745 750
Gly Thr Leu Val Thr Val Ser Ser His His His His His His
755 760 765
<210> 173
<211> 763
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro359 -形式4
<400> 173
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala Gly Met Lys
370 375 380
Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
385 390 395 400
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
405 410 415
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
420 425 430
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
435 440 445
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
450 455 460
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
465 470 475 480
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
500 505 510
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
515 520 525
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser
530 535 540
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
545 550 555 560
Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala
565 570 575
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
580 585 590
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr
595 600 605
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
610 615 620
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
625 630 635 640
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
645 650 655
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
660 665 670
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
675 680 685
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
690 695 700
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
705 710 715 720
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
725 730 735
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
740 745 750
Val Thr Val Ser Ser His His His His His His
755 760
<210> 174
<211> 752
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro364 -形式4
<400> 174
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly
355 360 365
Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu
370 375 380
Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys
385 390 395 400
Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg
405 410 415
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser
420 425 430
Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile
435 440 445
Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu
450 455 460
Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu
465 470 475 480
Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
485 490 495
Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
500 505 510
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
515 520 525
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
530 535 540
Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp
545 550 555 560
Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
565 570 575
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
580 585 590
Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
595 600 605
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
610 615 620
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
625 630 635 640
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
645 650 655
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
660 665 670
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
675 680 685
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
690 695 700
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
705 710 715 720
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
725 730 735
Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
740 745 750
<210> 175
<211> 753
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro388 -形式4
<400> 175
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro
355 360 365
Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val
370 375 380
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser
385 390 395 400
Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val
405 410 415
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly
420 425 430
Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr
435 440 445
Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser
450 455 460
Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser
465 470 475 480
Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
485 490 495
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
500 505 510
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
515 520 525
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
530 535 540
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
545 550 555 560
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
565 570 575
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
580 585 590
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
595 600 605
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
610 615 620
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
625 630 635 640
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
645 650 655
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
660 665 670
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
675 680 685
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
690 695 700
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
705 710 715 720
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
725 730 735
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
740 745 750
His
<210> 176
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro432-异质-形式2
<400> 176
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
370 375 380
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Ala Met Gly Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Val Ala Ile Asn
420 425 430
Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Tyr
465 470 475 480
Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr Asp Tyr
485 490 495
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly
500 505 510
Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 177
<211> 636
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro448- 双重靶向Hemis形式3
<400> 177
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Val
115 120 125
Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu Thr Leu Ser
130 135 140
Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe
145 150 155 160
Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp
165 170 175
Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser
195 200 205
Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ala Ala Gly
210 215 220
Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser
245 250 255
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
260 265 270
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
275 280 285
Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
290 295 300
Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
305 310 315 320
Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
325 330 335
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
340 345 350
Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
355 360 365
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly
370 375 380
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val
385 390 395 400
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
405 410 415
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
420 425 430
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
435 440 445
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
515 520 525
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
530 535 540
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
545 550 555 560
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
565 570 575
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
580 585 590
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
595 600 605
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
610 615 620
Leu Val Thr Val Ser Ser His His His His His His
625 630 635
<210> 178
<211> 636
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro449 双重靶向Hemis形式3
<400> 178
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu
130 135 140
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
145 150 155 160
Thr Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn
165 170 175
Glu Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr
180 185 190
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys
195 200 205
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala
210 215 220
Val Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser
245 250 255
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
260 265 270
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
275 280 285
Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
290 295 300
Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp
305 310 315 320
Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
325 330 335
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
340 345 350
Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
355 360 365
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly
370 375 380
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val
385 390 395 400
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
405 410 415
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
420 425 430
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
435 440 445
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
450 455 460
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
465 470 475 480
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
485 490 495
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
515 520 525
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
530 535 540
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
545 550 555 560
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
565 570 575
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
580 585 590
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
595 600 605
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
610 615 620
Leu Val Thr Val Ser Ser His His His His His His
625 630 635
<210> 179
<211> 636
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro450 双重靶向Hemis形式3
<400> 179
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Val
115 120 125
Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu Thr Leu Ser
130 135 140
Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe
145 150 155 160
Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp
165 170 175
Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser
195 200 205
Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala Ala Ala Gly
210 215 220
Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser
245 250 255
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
260 265 270
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
275 280 285
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
290 295 300
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
305 310 315 320
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
325 330 335
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
340 345 350
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly
355 360 365
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu
370 375 380
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
405 410 415
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
420 425 430
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
435 440 445
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
450 455 460
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
465 470 475 480
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
515 520 525
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
530 535 540
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
545 550 555 560
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
565 570 575
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
580 585 590
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
595 600 605
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
610 615 620
Leu Val Thr Val Ser Ser His His His His His His
625 630 635
<210> 180
<211> 636
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro451 双重靶向Hemis形式3
<400> 180
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu
130 135 140
Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
145 150 155 160
Thr Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn
165 170 175
Glu Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr
180 185 190
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys
195 200 205
Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala
210 215 220
Val Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser
245 250 255
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
260 265 270
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
275 280 285
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
290 295 300
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
305 310 315 320
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
325 330 335
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
340 345 350
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly
355 360 365
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu
370 375 380
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
405 410 415
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
420 425 430
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
435 440 445
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
450 455 460
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
465 470 475 480
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
515 520 525
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
530 535 540
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
545 550 555 560
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
565 570 575
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
580 585 590
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
595 600 605
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
610 615 620
Leu Val Thr Val Ser Ser His His His His His His
625 630 635
<210> 181
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro479-异质-形式2
<400> 181
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met
405 410 415
Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala
420 425 430
Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
565 570 575
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
625 630 635 640
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
645 650 655
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
660 665 670
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
675 680 685
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 182
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro480-异质-形式2
<400> 182
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu
370 375 380
Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
385 390 395 400
Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met Gly Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val Ile Asn
420 425 430
Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly
465 470 475 480
Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
565 570 575
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
625 630 635 640
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
645 650 655
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
660 665 670
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
675 680 685
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 183
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro495 -形式2
<400> 183
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val
420 425 430
Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp
565 570 575
Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
625 630 635 640
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
645 650 655
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys His Ala Met
660 665 670
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
675 680 685
Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 184
<211> 15
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成可裂解的接头 - MMP9-2
<400> 184
Ser Gly Gly Pro Gly Pro Ala Gly Leu Lys Gly Ala Pro Gly Ser
1 5 10 15
<210> 185
<211> 887
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro141
<400> 185
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn
565 570 575
Lys His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
625 630 635 640
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
645 650 655
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Ser Ala Met
660 665 670
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
675 680 685
Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Ala Tyr Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Thr Phe Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser
885
<210> 186
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro160
<400> 186
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr
260 265 270
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
275 280 285
Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
290 295 300
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr
305 310 315 320
Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
325 330 335
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
340 345 350
Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
355 360 365
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
370 375 380
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
385 390 395 400
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
405 410 415
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
420 425 430
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
435 440 445
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
450 455 460
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
465 470 475 480
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
485 490 495
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro
500 505 510
Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr
515 520 525
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
530 535 540
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp
545 550 555 560
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr
565 570 575
Ser Asn Lys His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
645 650 655
Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala
660 665 670
Ser Gly Phe Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala
675 680 685
Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn
690 695 700
Asn Tyr Ala Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
705 710 715 720
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
725 730 735
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
740 745 750
Gly Asn Ser Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu
755 760 765
Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly
770 775 780
Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 187
<211> 899
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro161
<400> 187
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys His
565 570 575
Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
580 585 590
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
595 600 605
Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr Lys
610 615 620
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
645 650 655
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
660 665 670
Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
675 680 685
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
690 695 700
Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
705 710 715 720
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
725 730 735
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr
740 745 750
Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
755 760 765
Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser
770 775 780
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
785 790 795 800
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
805 810 815
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
820 825 830
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
835 840 845
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
850 855 860
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
865 870 875 880
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
885 890 895
Val Ser Ser
<210> 188
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro162
<400> 188
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Val Tyr Ala Asp Ser Leu Glu Asp Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp
500 505 510
Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys
565 570 575
His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
690 695 700
Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
705 710 715 720
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
725 730 735
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser
740 745 750
Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
755 760 765
Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp Ser Leu Glu Asp Gly Gly
770 775 780
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
785 790 795 800
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
805 810 815
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
820 825 830
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
835 840 845
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
850 855 860
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
865 870 875 880
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
885 890 895
Val Thr Val Ser Ser
900
<210> 189
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro189
<400> 189
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Ala Arg Leu Gln Ser Ala Ala Pro Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln
500 505 510
Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys
565 570 575
His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
690 695 700
Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
705 710 715 720
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
725 730 735
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser
740 745 750
Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
755 760 765
Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln Ser Ala Ala Pro Gly Gly
770 775 780
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
785 790 795 800
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
805 810 815
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
820 825 830
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
835 840 845
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
850 855 860
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
865 870 875 880
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
885 890 895
Val Thr Val Ser Ser
900
<210> 190
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro164
<400> 190
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Lys Lys Leu Ala Asp Glu Pro Glu Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala
500 505 510
Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys
565 570 575
His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
690 695 700
Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
705 710 715 720
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
725 730 735
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser
740 745 750
Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
755 760 765
Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly
770 775 780
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
785 790 795 800
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
805 810 815
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
820 825 830
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
835 840 845
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
850 855 860
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
865 870 875 880
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
885 890 895
Val Thr Val Ser Ser
900
<210> 191
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro 191
<400> 191
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Leu Ser Gly Arg Ser Asp Asn His Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg
500 505 510
Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys
565 570 575
His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
690 695 700
Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
705 710 715 720
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
725 730 735
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser
740 745 750
Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
755 760 765
Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Gly
770 775 780
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
785 790 795 800
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
805 810 815
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
820 825 830
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
835 840 845
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
850 855 860
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
865 870 875 880
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
885 890 895
Val Thr Val Ser Ser
900
<210> 192
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro166
<400> 192
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser
245 250 255
Phe Thr Arg Gln Ala Arg Val Val Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln
500 505 510
Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Ser Asn Lys
565 570 575
His Ser Trp Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Gly Ser Arg Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Ser Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
690 695 700
Thr Ala Tyr Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
705 710 715 720
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
725 730 735
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser
740 745 750
Tyr Ile Thr Phe Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
755 760 765
Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln Ala Arg Val Val Gly Gly
770 775 780
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
785 790 795 800
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
805 810 815
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
820 825 830
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
835 840 845
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
850 855 860
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
865 870 875 880
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
885 890 895
Val Thr Val Ser Ser
900
<210> 193
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro169
<400> 193
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly His Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
565 570 575
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
690 695 700
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
705 710 715 720
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
725 730 735
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
740 745 750
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
755 760 765
Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro
770 775 780
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
785 790 795 800
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
805 810 815
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
820 825 830
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
835 840 845
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
850 855 860
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
865 870 875 880
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
885 890 895
Val Thr Val Ser Ser
900
<210> 194
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro170
<400> 194
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Val Tyr Ala Asp Ser Leu Glu Asp Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp
500 505 510
Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp
565 570 575
Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Ser Val Tyr Ala Asp Ser Leu Glu Asp
770 775 780
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 195
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro171
<400> 195
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Ala Arg Leu Gln Ser Ala Ala Pro Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln
500 505 510
Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp
565 570 575
Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Ser Ala Arg Leu Gln Ser Ala Ala Pro
770 775 780
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 196
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro172
<400> 196
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Lys Lys Leu Ala Asp Glu Pro Glu Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala
500 505 510
Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp
565 570 575
Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu
770 775 780
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 197
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro173
<400> 197
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Leu Ser Gly Arg Ser Asp Asn His Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg
500 505 510
Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp
565 570 575
Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His
770 775 780
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 198
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro174
<400> 198
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser
245 250 255
Phe Thr Arg Gln Ala Arg Val Val Gly Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn
405 410 415
Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
420 425 430
Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
450 455 460
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
465 470 475 480
Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln
500 505 510
Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro
515 520 525
Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser
530 535 540
Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln
545 550 555 560
Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp
565 570 575
Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Ser Phe Thr Arg Gln Ala Arg Val Val
770 775 780
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 199
<211> 888
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro176
<400> 199
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp
565 570 575
Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
625 630 635 640
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
645 650 655
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met
660 665 670
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
675 680 685
Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser
690 695 700
Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala
705 710 715 720
Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr
725 730 735
Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala
740 745 750
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
770 775 780
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
785 790 795 800
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
805 810 815
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
820 825 830
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
835 840 845
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
850 855 860
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
865 870 875 880
Gly Thr Leu Val Thr Val Ser Ser
885
<210> 200
<211> 892
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro178
<400> 200
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gln Thr Val Val Thr
260 265 270
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
275 280 285
Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
290 295 300
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr
305 310 315 320
Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
325 330 335
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
340 345 350
Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
355 360 365
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
370 375 380
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
385 390 395 400
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
405 410 415
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
420 425 430
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
435 440 445
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
450 455 460
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
465 470 475 480
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
485 490 495
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
500 505 510
Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val
515 520 525
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
530 535 540
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
545 550 555 560
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
565 570 575
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
580 585 590
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
595 600 605
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
610 615 620
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
645 650 655
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
660 665 670
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
675 680 685
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
690 695 700
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
705 710 715 720
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
725 730 735
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
740 745 750
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
755 760 765
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
770 775 780
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
785 790 795 800
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
805 810 815
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
820 825 830
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
835 840 845
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
850 855 860
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
865 870 875 880
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 201
<211> 894
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro179
<400> 201
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Ser Gln Thr Val
260 265 270
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
275 280 285
Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
290 295 300
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
305 310 315 320
Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
325 330 335
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
340 345 350
Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val
355 360 365
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
370 375 380
Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr
385 390 395 400
Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg
405 410 415
Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu
420 425 430
Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp
435 440 445
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr
450 455 460
Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr
465 470 475 480
Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu
485 490 495
Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly
500 505 510
Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr
515 520 525
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
530 535 540
Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
545 550 555 560
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
565 570 575
Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser
580 585 590
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
595 600 605
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg
610 615 620
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
625 630 635 640
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
645 650 655
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
660 665 670
Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
675 680 685
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp
690 695 700
Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
705 710 715 720
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
725 730 735
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser
740 745 750
Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
755 760 765
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
770 775 780
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser
785 790 795 800
Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val
805 810 815
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly
820 825 830
Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr
835 840 845
Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser
850 855 860
Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser
865 870 875 880
Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 202
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro180
<400> 202
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Ser Gln
260 265 270
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
275 280 285
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
290 295 300
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
305 310 315 320
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
325 330 335
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
340 345 350
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
355 360 365
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
370 375 380
Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val
385 390 395 400
Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr
405 410 415
Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu
420 425 430
Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr
435 440 445
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
450 455 460
Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
465 470 475 480
Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu
485 490 495
Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
500 505 510
Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser
515 520 525
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
530 535 540
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
545 550 555 560
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
565 570 575
Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg
580 585 590
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
595 600 605
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser
610 615 620
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
770 775 780
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg
785 790 795 800
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser
805 810 815
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile
820 825 830
Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg
835 840 845
Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met
850 855 860
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly
865 870 875 880
Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890 895
<210> 203
<211> 898
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro181
<400> 203
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Gly
260 265 270
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
275 280 285
Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser
290 295 300
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
305 310 315 320
Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg
325 330 335
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
340 345 350
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser
355 360 365
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
370 375 380
Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly
385 390 395 400
Ser Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly
405 410 415
Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly
420 425 430
Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr
435 440 445
Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
450 455 460
Ala Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp
465 470 475 480
Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly
485 490 495
Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val
500 505 510
Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly
515 520 525
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
530 535 540
Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr
545 550 555 560
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
565 570 575
Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro
580 585 590
Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu
595 600 605
Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp
610 615 620
Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
625 630 635 640
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
645 650 655
Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala
660 665 670
Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala
675 680 685
Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp
690 695 700
Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr
705 710 715 720
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
725 730 735
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn
740 745 750
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
755 760 765
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu
770 775 780
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser
785 790 795 800
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly
805 810 815
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
820 825 830
Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys
835 840 845
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu
850 855 860
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr
865 870 875 880
Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val
885 890 895
Ser Ser
<210> 204
<211> 891
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro182
<400> 204
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Pro Ala Gly Met Lys Gly Leu Gly Gln Thr Val Val Thr
260 265 270
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
275 280 285
Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
290 295 300
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr
305 310 315 320
Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
325 330 335
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
340 345 350
Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
355 360 365
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
370 375 380
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
385 390 395 400
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
405 410 415
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
420 425 430
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
435 440 445
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
450 455 460
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
465 470 475 480
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
485 490 495
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro
500 505 510
Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr
515 520 525
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
530 535 540
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
545 550 555 560
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
565 570 575
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
580 585 590
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
595 600 605
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
610 615 620
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
645 650 655
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
660 665 670
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
675 680 685
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
690 695 700
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
705 710 715 720
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
725 730 735
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
740 745 750
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
755 760 765
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
770 775 780
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
785 790 795 800
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
805 810 815
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
820 825 830
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
835 840 845
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
850 855 860
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
865 870 875 880
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 205
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro183
<400> 205
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Ser Gly Pro Ala Gly Met Lys Gly Leu Gly Ser Gln Thr Val
260 265 270
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
275 280 285
Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
290 295 300
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
305 310 315 320
Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser
325 330 335
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
340 345 350
Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val
355 360 365
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
370 375 380
Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr
385 390 395 400
Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg
405 410 415
Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu
420 425 430
Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp
435 440 445
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr
450 455 460
Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr
465 470 475 480
Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu
485 490 495
Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly
500 505 510
Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val
515 520 525
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
530 535 540
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
545 550 555 560
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
565 570 575
Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly
580 585 590
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
595 600 605
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
610 615 620
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
625 630 635 640
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
645 650 655
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
660 665 670
Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
675 680 685
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp
690 695 700
Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
705 710 715 720
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
725 730 735
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr
740 745 750
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
770 775 780
Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys
785 790 795 800
Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg
805 810 815
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser
820 825 830
Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile
835 840 845
Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu
850 855 860
Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu
865 870 875 880
Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 206
<211> 895
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro184
<400> 206
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Ser Gly Pro Ala Gly Met Lys Gly Leu Gly Gly Ser Gln
260 265 270
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
275 280 285
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
290 295 300
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
305 310 315 320
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
325 330 335
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
340 345 350
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
355 360 365
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
370 375 380
Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val
385 390 395 400
Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr
405 410 415
Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu
420 425 430
Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr
435 440 445
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
450 455 460
Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala
465 470 475 480
Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu
485 490 495
Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser
500 505 510
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
515 520 525
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
530 535 540
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
545 550 555 560
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
565 570 575
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
580 585 590
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
595 600 605
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
610 615 620
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
690 695 700
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
705 710 715 720
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
725 730 735
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
740 745 750
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
755 760 765
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
770 775 780
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
785 790 795 800
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
805 810 815
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
820 825 830
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
835 840 845
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
850 855 860
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
865 870 875 880
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890 895
<210> 207
<211> 897
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro185
<400> 207
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Pro Ala Gly Met Lys Gly Leu Gly Gly Gly
260 265 270
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
275 280 285
Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser
290 295 300
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
305 310 315 320
Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg
325 330 335
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
340 345 350
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser
355 360 365
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
370 375 380
Gly Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly
385 390 395 400
Ser Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly
405 410 415
Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly
420 425 430
Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr
435 440 445
Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
450 455 460
Ala Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp
465 470 475 480
Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly
485 490 495
Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val
500 505 510
Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly
515 520 525
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
530 535 540
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser
545 550 555 560
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
565 570 575
Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala
580 585 590
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
595 600 605
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr
610 615 620
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
625 630 635 640
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
645 650 655
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
660 665 670
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
675 680 685
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
690 695 700
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
705 710 715 720
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
725 730 735
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
740 745 750
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
755 760 765
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
770 775 780
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu
785 790 795 800
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met
805 810 815
Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser
820 825 830
Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly
835 840 845
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln
850 855 860
Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile
865 870 875 880
Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser
885 890 895
Ser
<210> 208
<211> 889
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro188
<400> 208
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Pro Ala Gly Met Lys Gly Leu Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser
885
<210> 209
<211> 897
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro189
<400> 209
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly
625 630 635 640
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
645 650 655
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
660 665 670
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
675 680 685
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
690 695 700
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
705 710 715 720
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
725 730 735
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
740 745 750
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
755 760 765
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
770 775 780
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu
785 790 795 800
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met
805 810 815
Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser
820 825 830
Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly
835 840 845
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln
850 855 860
Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile
865 870 875 880
Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser
885 890 895
Ser
<210> 210
<211> 898
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro190
<400> 210
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys
500 505 510
Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
645 650 655
Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala
660 665 670
Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala
675 680 685
Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp
690 695 700
Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr
705 710 715 720
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
725 730 735
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn
740 745 750
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
755 760 765
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu
770 775 780
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser
785 790 795 800
Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly
805 810 815
Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser
820 825 830
Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys
835 840 845
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu
850 855 860
Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr
865 870 875 880
Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val
885 890 895
Ser Ser
<210> 211
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro191
<400> 211
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly
625 630 635 640
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
645 650 655
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
660 665 670
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
675 680 685
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
690 695 700
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
705 710 715 720
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
725 730 735
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
740 745 750
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
755 760 765
Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly
770 775 780
Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
785 790 795 800
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
805 810 815
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
820 825 830
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
835 840 845
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
850 855 860
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
865 870 875 880
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
885 890 895
Thr Leu Val Thr Val Ser Ser
900
<210> 212
<211> 905
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro192
<400> 212
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys
500 505 510
Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
645 650 655
Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala
660 665 670
Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala
675 680 685
Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp
690 695 700
Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr
705 710 715 720
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
725 730 735
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn
740 745 750
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
755 760 765
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu
770 775 780
Pro Glu Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
785 790 795 800
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
805 810 815
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
820 825 830
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
835 840 845
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
850 855 860
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
865 870 875 880
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
885 890 895
Gln Gly Thr Leu Val Thr Val Ser Ser
900 905
<210> 213
<211> 763
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro193
<400> 213
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala Gly Met Lys
370 375 380
Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
385 390 395 400
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
405 410 415
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
420 425 430
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
435 440 445
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
450 455 460
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
465 470 475 480
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
485 490 495
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
500 505 510
Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr
515 520 525
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
530 535 540
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
545 550 555 560
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
565 570 575
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
580 585 590
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
595 600 605
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
610 615 620
Gly Gly Gly Thr Lys Leu Thr Val Leu Ser Gly Gly Pro Gly Pro Ala
625 630 635 640
Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser Gly
645 650 655
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
660 665 670
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
675 680 685
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
690 695 700
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
705 710 715 720
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
725 730 735
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
740 745 750
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
755 760
<210> 214
<211> 892
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro195
<400> 214
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Met Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr
100 105 110
Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly
115 120 125
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
130 135 140
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
145 150 155 160
Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro
165 170 175
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
180 185 190
Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser
195 200 205
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
210 215 220
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly
225 230 235 240
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
245 250 255
Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
260 265 270
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
275 280 285
Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
290 295 300
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
305 310 315 320
Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
325 330 335
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
340 345 350
Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe
355 360 365
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
370 375 380
Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly
385 390 395 400
Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser
405 410 415
Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe
420 425 430
Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser
435 440 445
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val
450 455 460
Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr
465 470 475 480
Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr
485 490 495
Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly
500 505 510
Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val
515 520 525
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
530 535 540
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
545 550 555 560
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
565 570 575
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
580 585 590
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
595 600 605
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
610 615 620
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
645 650 655
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
660 665 670
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
675 680 685
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
690 695 700
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
705 710 715 720
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
725 730 735
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
740 745 750
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
755 760 765
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
770 775 780
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
785 790 795 800
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
805 810 815
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
820 825 830
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
835 840 845
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
850 855 860
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
865 870 875 880
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890
<210> 215
<211> 889
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro196
<400> 215
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
130 135 140
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala
145 150 155 160
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln
165 170 175
Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr
180 185 190
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
195 200 205
Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu
210 215 220
Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
225 230 235 240
Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
245 250 255
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
260 265 270
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
275 280 285
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
290 295 300
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
305 310 315 320
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
325 330 335
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
340 345 350
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
355 360 365
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser
885
<210> 216
<211> 888
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro197
<400> 216
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser
515 520 525
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
530 535 540
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln
545 550 555 560
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
565 570 575
Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe
580 585 590
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
595 600 605
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly
610 615 620
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
625 630 635 640
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
645 650 655
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
660 665 670
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
675 680 685
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
690 695 700
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
705 710 715 720
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
725 730 735
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
740 745 750
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
755 760 765
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
770 775 780
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
785 790 795 800
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
805 810 815
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
820 825 830
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
835 840 845
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
850 855 860
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
865 870 875 880
Gly Thr Leu Val Thr Val Ser Ser
885
<210> 217
<211> 888
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro198
<400> 217
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
130 135 140
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala
145 150 155 160
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln
165 170 175
Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr
180 185 190
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
195 200 205
Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu
210 215 220
Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
225 230 235 240
Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
245 250 255
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
260 265 270
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
275 280 285
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
290 295 300
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
305 310 315 320
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
325 330 335
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
340 345 350
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
355 360 365
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Glu Val Gln Leu Val Glu Ser
515 520 525
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
530 535 540
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln
545 550 555 560
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
565 570 575
Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe
580 585 590
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
595 600 605
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly
610 615 620
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
625 630 635 640
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
645 650 655
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
660 665 670
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
675 680 685
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
690 695 700
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
705 710 715 720
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
725 730 735
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
740 745 750
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
755 760 765
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
770 775 780
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
785 790 795 800
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
805 810 815
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
820 825 830
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
835 840 845
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
850 855 860
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
865 870 875 880
Gly Thr Leu Val Thr Val Ser Ser
885
<210> 218
<211> 885
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro199
<400> 218
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu
370 375 380
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Thr Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn Leu Met
405 410 415
Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala Arg
420 425 430
Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys Gly Arg
435 440 445
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met
450 455 460
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn Leu Leu
465 470 475 480
Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln Gly Thr
485 490 495
Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys
500 505 510
Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
515 520 525
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
530 535 540
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
545 550 555 560
Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys
565 570 575
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
580 585 590
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
595 600 605
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
610 615 620
Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
625 630 635 640
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
645 650 655
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val
660 665 670
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
675 680 685
Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp
690 695 700
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
705 710 715 720
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
725 730 735
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
740 745 750
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
755 760 765
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
770 775 780
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
785 790 795 800
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
805 810 815
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
820 825 830
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
835 840 845
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
850 855 860
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
865 870 875 880
Val Thr Val Ser Ser
885
<210> 219
<211> 886
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro200
<400> 219
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser
20 25 30
Ile Asn Leu Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu
35 40 45
Leu Val Ala Arg Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser
50 55 60
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
65 70 75 80
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Asn Leu Leu Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu
370 375 380
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Thr Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Thr Gly Ser Ile Phe Ser Ile Asn Leu Met
405 410 415
Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val Ala Arg
420 425 430
Ile Thr Ser Gly Asp Ser Thr Val Tyr Ala Asp Ser Val Lys Gly Arg
435 440 445
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met
450 455 460
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn Leu Leu
465 470 475 480
Leu Arg Ser Ser Pro Gly Ala Thr Thr Pro Tyr Trp Gly Gln Gly Thr
485 490 495
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys Leu Ala Asp Glu
500 505 510
Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
515 520 525
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
530 535 540
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
545 550 555 560
Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp
565 570 575
Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
580 585 590
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
595 600 605
Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
610 615 620
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
625 630 635 640
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
645 650 655
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
660 665 670
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
675 680 685
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
690 695 700
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
705 710 715 720
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
725 730 735
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
740 745 750
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
755 760 765
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
770 775 780
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
785 790 795 800
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
805 810 815
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
820 825 830
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
835 840 845
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
850 855 860
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
865 870 875 880
Leu Val Thr Val Ser Ser
885
<210> 220
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro189 (在
失活的aCD3 结构域之间具有长接头的Pro186)
<400> 220
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly
625 630 635 640
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
645 650 655
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
660 665 670
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
675 680 685
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
690 695 700
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
705 710 715 720
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
725 730 735
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
740 745 750
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
755 760 765
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
770 775 780
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu
785 790 795 800
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met
805 810 815
Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser
820 825 830
Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly
835 840 845
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln
850 855 860
Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile
865 870 875 880
Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser
885 890 895
Ser His His His His His His
900
<210> 221
<211> 636
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro206 (Pro186活性结构域 + aHSA)
<400> 221
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
515 520 525
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
530 535 540
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
545 550 555 560
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
565 570 575
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
580 585 590
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
595 600 605
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
610 615 620
Leu Val Thr Val Ser Ser His His His His His His
625 630 635
<210> 222
<211> 513
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro227 (Pro22 aB7H3 hF7)
<400> 222
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
130 135 140
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
145 150 155 160
Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys
165 170 175
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
180 185 190
Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
195 200 205
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
210 215 220
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser
225 230 235 240
Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
245 250 255
Ser Ser Gly Gly Gly Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Gly
260 265 270
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
275 280 285
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
290 295 300
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
305 310 315 320
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
325 330 335
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
340 345 350
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
355 360 365
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
370 375 380
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
385 390 395 400
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
405 410 415
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
420 425 430
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
435 440 445
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
450 455 460
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
465 470 475 480
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
485 490 495
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
500 505 510
His
<210> 223
<211> 511
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro228 (Pro22 aB7H3 hF12)
<400> 223
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
130 135 140
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
145 150 155 160
Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
165 170 175
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr
180 185 190
Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
195 200 205
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
210 215 220
Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile
225 230 235 240
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250 255
Gly Gly Gly Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Gly Gly Ser
260 265 270
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
275 280 285
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
290 295 300
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
305 310 315 320
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
325 330 335
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
340 345 350
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
355 360 365
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
370 375 380
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
385 390 395 400
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
405 410 415
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
420 425 430
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
435 440 445
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
450 455 460
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
465 470 475 480
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
485 490 495
Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
500 505 510
<210> 224
<211> 512
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro244 (Pro51 aB7H3 hF7)
<400> 224
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
115 120 125
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
130 135 140
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
145 150 155 160
Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys
165 170 175
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala
180 185 190
Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp
195 200 205
Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu
210 215 220
Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser
225 230 235 240
Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
245 250 255
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
260 265 270
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
275 280 285
Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser
290 295 300
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
305 310 315 320
Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg
325 330 335
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
340 345 350
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser
355 360 365
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
370 375 380
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
385 390 395 400
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
405 410 415
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
420 425 430
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
435 440 445
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
450 455 460
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
465 470 475 480
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
485 490 495
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
500 505 510
<210> 225
<211> 510
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro245 (Pro51 aB7H3 hF12)
<400> 225
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
130 135 140
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
145 150 155 160
Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
165 170 175
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr
180 185 190
Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
195 200 205
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
210 215 220
Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile
225 230 235 240
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
260 265 270
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
275 280 285
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
290 295 300
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
305 310 315 320
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
325 330 335
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
340 345 350
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
355 360 365
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly
370 375 380
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
385 390 395 400
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
405 410 415
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
420 425 430
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
435 440 445
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
450 455 460
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
465 470 475 480
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
485 490 495
Gly Thr Leu Val Thr Val Ser Ser His His His His His His
500 505 510
<210> 226
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro247 (具有Meprin
接头的人源化Pro186)
<400> 226
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Lys Lys
500 505 510
Leu Ala Asp Glu Pro Glu Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 227
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro248 (具有CathS 接头的人源化Pro186)
<400> 227
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Ala Arg
500 505 510
Leu Gln Ser Ala Ala Pro Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 228
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro249 (具有
Meprin/颗粒酶B接头的人源化Pro186)
<400> 228
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Val Tyr
500 505 510
Ala Asp Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 229
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro250 (具有S9 -
CathS/MMP9 接头的人源化Pro186)
<400> 229
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ala Arg Leu Gln Ser
500 505 510
Ala Ala Pro Ala Gly Leu Lys Gly Ala Gly Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 230
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro251 (具有ST14(MS)
接头的人源化Pro186)
<400> 230
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Leu Ser
500 505 510
Gly Arg Ser Asp Asn His Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 231
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro252 (具有ST14(MV)
接头的人源化Pro186)
<400> 231
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Phe Thr
500 505 510
Arg Gln Ala Arg Val Val Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 232
<211> 897
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro253 (具有MMP9v 接头的人源化Pro186)
<400> 232
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Ser Gly Gly Pro Gly
500 505 510
Pro Ala Gly Met His Gly Leu Pro Gly Gly Ser Gln Thr Val Val Thr
515 520 525
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
530 535 540
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
545 550 555 560
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
565 570 575
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
580 585 590
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
595 600 605
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
610 615 620
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
645 650 655
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
660 665 670
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
675 680 685
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
690 695 700
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
705 710 715 720
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
725 730 735
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
740 745 750
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
755 760 765
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
770 775 780
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
785 790 795 800
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
805 810 815
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
820 825 830
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
835 840 845
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
850 855 860
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
865 870 875 880
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
885 890 895
His
<210> 233
<211> 902
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro261 (具有长活性
结构域aCD3 接头的人源化Pro186)
<400> 233
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
275 280 285
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
290 295 300
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
305 310 315 320
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
325 330 335
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
340 345 350
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
355 360 365
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
370 375 380
Ser Gly Gly Gly Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val
385 390 395 400
Val Arg Pro Gly Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg
405 410 415
Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys
420 425 430
Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly
435 440 445
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
450 455 460
Lys Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr
465 470 475 480
Ala Leu Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr
485 490 495
Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
500 505 510
Ser Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser
515 520 525
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
530 535 540
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
545 550 555 560
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
565 570 575
Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg
580 585 590
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
595 600 605
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser
610 615 620
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
770 775 780
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg
785 790 795 800
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser
805 810 815
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile
820 825 830
Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg
835 840 845
Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met
850 855 860
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly
865 870 875 880
Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890 895
His His His His His His
900
<210> 234
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro294 (FL haEGFR2 MMP9 接头)
<400> 234
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr
100 105 110
Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
115 120 125
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
130 135 140
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
145 150 155 160
Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro
165 170 175
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
180 185 190
Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser
195 200 205
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
210 215 220
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly
225 230 235 240
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
245 250 255
Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
260 265 270
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
275 280 285
Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
290 295 300
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
305 310 315 320
Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
325 330 335
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
340 345 350
Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe
355 360 365
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
370 375 380
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
385 390 395 400
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser
405 410 415
Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe
420 425 430
Val Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser
435 440 445
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
450 455 460
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
465 470 475 480
Cys Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp
485 490 495
Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
500 505 510
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
515 520 525
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
530 535 540
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
545 550 555 560
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
565 570 575
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
580 585 590
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
595 600 605
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
610 615 620
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
690 695 700
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
705 710 715 720
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
725 730 735
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
740 745 750
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
755 760 765
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
770 775 780
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
785 790 795 800
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
805 810 815
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
820 825 830
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
835 840 845
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
850 855 860
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
865 870 875 880
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
885 890 895
His His His His His
900
<210> 235
<211> 895
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro295 (FL aB7H3 hF7 NC 接头)
<400> 235
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val
420 425 430
Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 236
<211> 891
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro296 (FL aB7H3 hF12 NC 接头)
<400> 236
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu
370 375 380
Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
385 390 395 400
Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala Ile Asn
420 425 430
Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly
465 470 475 480
Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr
485 490 495
Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
500 505 510
Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
515 520 525
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
530 535 540
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
545 550 555 560
Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys
565 570 575
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
580 585 590
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
595 600 605
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
610 615 620
Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
625 630 635 640
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
645 650 655
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val
660 665 670
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
675 680 685
Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp
690 695 700
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
705 710 715 720
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
725 730 735
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
740 745 750
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
755 760 765
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
770 775 780
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
785 790 795 800
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
805 810 815
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
820 825 830
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
835 840 845
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
850 855 860
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
865 870 875 880
Val Thr Val Ser Ser His His His His His His
885 890
<210> 237
<211> 876
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro297 (FL aFOLR1 h77-2 KLK7.6 接头)
<400> 237
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu
405 410 415
Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala
420 425 430
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
435 440 445
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
450 455 460
Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr
465 470 475 480
Leu Val Thr Val Ser Ser Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala
485 490 495
Gly Arg Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
500 505 510
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
515 520 525
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
530 535 540
Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp
545 550 555 560
Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
565 570 575
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
580 585 590
Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
595 600 605
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
610 615 620
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
625 630 635 640
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
645 650 655
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
660 665 670
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
675 680 685
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
690 695 700
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
705 710 715 720
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
725 730 735
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
740 745 750
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
755 760 765
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
770 775 780
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
785 790 795 800
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
805 810 815
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
820 825 830
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
835 840 845
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
850 855 860
Leu Val Thr Val Ser Ser His His His His His His
865 870 875
<210> 238
<211> 876
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro298 (FL aFOLR1 h77-2 KLK7.11 接头)
<400> 238
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu
405 410 415
Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala
420 425 430
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
435 440 445
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
450 455 460
Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr
465 470 475 480
Leu Val Thr Val Ser Ser Ser Gly Gly Gly Arg Asn Val Tyr Ser Ala
485 490 495
Gly Gly Gly Ser Gly Gly Gln Thr Val Val Thr Gln Glu Pro Ser Leu
500 505 510
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
515 520 525
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
530 535 540
Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp
545 550 555 560
Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
565 570 575
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
580 585 590
Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
595 600 605
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
610 615 620
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
625 630 635 640
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
645 650 655
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
660 665 670
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
675 680 685
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
690 695 700
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
705 710 715 720
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
725 730 735
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
740 745 750
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
755 760 765
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
770 775 780
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
785 790 795 800
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
805 810 815
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
820 825 830
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
835 840 845
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
850 855 860
Leu Val Thr Val Ser Ser His His His His His His
865 870 875
<210> 239
<211> 876
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro299 (FL aFOLR1 h77-2 NC 接头)
<400> 239
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
355 360 365
Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
370 375 380
Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
385 390 395 400
Val Ser Asn Ser Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu
405 410 415
Arg Glu Phe Val Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala
420 425 430
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
435 440 445
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
450 455 460
Tyr Val Cys Asn Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr
465 470 475 480
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
485 490 495
Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
500 505 510
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr
515 520 525
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
530 535 540
Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp
545 550 555 560
Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
565 570 575
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
580 585 590
Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
595 600 605
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
610 615 620
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu
625 630 635 640
Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp
645 650 655
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg
660 665 670
Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys
675 680 685
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
690 695 700
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
705 710 715 720
Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
725 730 735
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
740 745 750
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
755 760 765
Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
770 775 780
Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
785 790 795 800
Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala
805 810 815
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr
820 825 830
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val
835 840 845
Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr
850 855 860
Leu Val Thr Val Ser Ser His His His His His His
865 870 875
<210> 240
<211> 502
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro300 (Pro51 aFOLR1 h77-2)
<400> 240
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
115 120 125
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
130 135 140
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
165 170 175
Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg
180 185 190
Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met
195 200 205
Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His
210 215 220
Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln
225 230 235 240
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
245 250 255
Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
370 375 380
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg
385 390 395 400
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser
405 410 415
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile
420 425 430
Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg
435 440 445
Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met
450 455 460
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly
465 470 475 480
Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
485 490 495
His His His His His His
500
<210> 241
<211> 874
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro301 (FL aFOLR1 h59.3 KLK7.6 接头)
<400> 241
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
355 360 365
Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
370 375 380
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe
385 390 395 400
Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg
405 410 415
Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp
420 425 430
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
435 440 445
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
450 455 460
Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val
465 470 475 480
Thr Val Ser Ser Ser Gly Gly Gly Gln Asn Pro Tyr Ser Ala Gly Arg
485 490 495
Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
500 505 510
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
515 520 525
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln
530 535 540
Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly
545 550 555 560
Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
565 570 575
Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val
580 585 590
Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
595 600 605
Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
610 615 620
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
625 630 635 640
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg
645 650 655
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
660 665 670
Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg
675 680 685
Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met
690 695 700
Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His
705 710 715 720
Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln
725 730 735
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
740 745 750
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
755 760 765
Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys
770 775 780
Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
785 790 795 800
Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser
805 810 815
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu
820 825 830
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
835 840 845
Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val
850 855 860
Thr Val Ser Ser His His His His His His
865 870
<210> 242
<211> 874
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro302 (FL aFOLR1 h59.3 KLK7.11 接头)
<400> 242
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
355 360 365
Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
370 375 380
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe
385 390 395 400
Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg
405 410 415
Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp
420 425 430
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
435 440 445
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
450 455 460
Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val
465 470 475 480
Thr Val Ser Ser Ser Gly Gly Gly Arg Asn Val Tyr Ser Ala Gly Gly
485 490 495
Gly Ser Gly Gly Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
500 505 510
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
515 520 525
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln
530 535 540
Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly
545 550 555 560
Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
565 570 575
Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val
580 585 590
Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
595 600 605
Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
610 615 620
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
625 630 635 640
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg
645 650 655
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
660 665 670
Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg
675 680 685
Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met
690 695 700
Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His
705 710 715 720
Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln
725 730 735
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
740 745 750
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
755 760 765
Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys
770 775 780
Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
785 790 795 800
Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser
805 810 815
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu
820 825 830
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
835 840 845
Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val
850 855 860
Thr Val Ser Ser His His His His His His
865 870
<210> 243
<211> 874
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro303 (FL aFOLR1 h59.3 NC 接头)
<400> 243
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
355 360 365
Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
370 375 380
Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe
385 390 395 400
Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg
405 410 415
Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp
420 425 430
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr
435 440 445
Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr
450 455 460
Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val
465 470 475 480
Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser
485 490 495
Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val
500 505 510
Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala
515 520 525
Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln
530 535 540
Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly
545 550 555 560
Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu
565 570 575
Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val
580 585 590
Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr
595 600 605
Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
610 615 620
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
625 630 635 640
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg
645 650 655
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
660 665 670
Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg
675 680 685
Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met
690 695 700
Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His
705 710 715 720
Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln
725 730 735
Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly
740 745 750
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
755 760 765
Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys
770 775 780
Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
785 790 795 800
Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser
805 810 815
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu
820 825 830
Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr
835 840 845
Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val
850 855 860
Thr Val Ser Ser His His His His His His
865 870
<210> 244
<211> 501
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro304 (Pro51 aFOLR1 h59.3)
<400> 244
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
245 250 255
Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu
260 265 270
Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr
275 280 285
Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro
290 295 300
Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro
305 310 315 320
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
325 330 335
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
340 345 350
Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
355 360 365
Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
370 375 380
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
385 390 395 400
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
405 410 415
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
420 425 430
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
465 470 475 480
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
485 490 495
His His His His His
500
<210> 245
<211> 882
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro305 (FL aFOLR1 h22.4 KLK7.6 接头)
<400> 245
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Gly
485 490 495
Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val
500 505 510
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
515 520 525
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
530 535 540
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
545 550 555 560
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
565 570 575
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
580 585 590
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
595 600 605
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
610 615 620
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
625 630 635 640
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
645 650 655
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
660 665 670
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
675 680 685
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
690 695 700
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
705 710 715 720
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
725 730 735
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
755 760 765
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
770 775 780
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
785 790 795 800
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
805 810 815
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
820 825 830
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
835 840 845
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
850 855 860
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His
865 870 875 880
His His
<210> 246
<211> 882
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro306 (FL aFOLR1 h22.4 KLK7.11 接头)
<400> 246
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Gly
485 490 495
Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val
500 505 510
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
515 520 525
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
530 535 540
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
545 550 555 560
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
565 570 575
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
580 585 590
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
595 600 605
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
610 615 620
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
625 630 635 640
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
645 650 655
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
660 665 670
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
675 680 685
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
690 695 700
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
705 710 715 720
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
725 730 735
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
755 760 765
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
770 775 780
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
785 790 795 800
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
805 810 815
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
820 825 830
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
835 840 845
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
850 855 860
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His
865 870 875 880
His His
<210> 247
<211> 882
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro307 (FL aFOLR1 h22.4 NC 接头)
<400> 247
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
485 490 495
Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
500 505 510
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
515 520 525
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
530 535 540
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
545 550 555 560
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
565 570 575
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
580 585 590
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
595 600 605
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
610 615 620
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
625 630 635 640
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
645 650 655
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
660 665 670
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
675 680 685
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
690 695 700
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
705 710 715 720
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
725 730 735
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
740 745 750
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
755 760 765
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
770 775 780
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
785 790 795 800
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
805 810 815
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
820 825 830
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
835 840 845
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
850 855 860
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His
865 870 875 880
His His
<210> 248
<211> 505
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro308 (Pro51 aFOLR1 h22.4)
<400> 248
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
115 120 125
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
130 135 140
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile
145 150 155 160
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
165 170 175
Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val
180 185 190
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
195 200 205
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
210 215 220
Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
225 230 235 240
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln
260 265 270
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
275 280 285
Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
290 295 300
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys
305 310 315 320
Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
325 330 335
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
340 345 350
Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
355 360 365
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser
370 375 380
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
385 390 395 400
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
405 410 415
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
420 425 430
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
435 440 445
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
450 455 460
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
465 470 475 480
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
485 490 495
Val Ser Ser His His His His His His
500 505
<210> 249
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro335 (FL aEGFR2 NC 接头)
<400> 249
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr
20 25 30
Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr
100 105 110
Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
115 120 125
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
130 135 140
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
145 150 155 160
Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro
165 170 175
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn
180 185 190
Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser
195 200 205
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
210 215 220
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly
225 230 235 240
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
245 250 255
Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
260 265 270
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
275 280 285
Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
290 295 300
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
305 310 315 320
Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
325 330 335
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
340 345 350
Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe
355 360 365
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
370 375 380
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
385 390 395 400
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser
405 410 415
Tyr Ala Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe
420 425 430
Val Val Ala Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser
435 440 445
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu
450 455 460
Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr
465 470 475 480
Cys Ala Ala Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp
485 490 495
Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
500 505 510
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
515 520 525
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
530 535 540
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
545 550 555 560
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
565 570 575
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
580 585 590
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
595 600 605
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
610 615 620
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
690 695 700
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
705 710 715 720
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
725 730 735
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
740 745 750
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
755 760 765
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
770 775 780
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
785 790 795 800
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
805 810 815
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
820 825 830
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
835 840 845
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
850 855 860
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
865 870 875 880
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
885 890 895
His His His His His
900
<210> 250
<211> 894
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro345 (人源化Pro186 Vli2 结构域 MMP9
接头)
<400> 250
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro
500 505 510
Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp
565 570 575
Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
625 630 635 640
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
645 650 655
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met
660 665 670
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
675 680 685
Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser
690 695 700
Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala
705 710 715 720
Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr
725 730 735
Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala
740 745 750
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
770 775 780
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
785 790 795 800
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
805 810 815
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
820 825 830
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
835 840 845
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
850 855 860
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
865 870 875 880
Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 251
<211> 894
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro346 (人源化Pro186 Vli2 结构域 NC
接头)
<400> 251
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly Ser Leu
385 390 395 400
Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly
500 505 510
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Asp
565 570 575
Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
580 585 590
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
595 600 605
Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
610 615 620
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
625 630 635 640
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
645 650 655
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met
660 665 670
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
675 680 685
Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser
690 695 700
Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala
705 710 715 720
Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr
725 730 735
Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala
740 745 750
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
770 775 780
Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe
785 790 795 800
Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys
805 810 815
Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu
820 825 830
Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
835 840 845
Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr
850 855 860
Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln
865 870 875 880
Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 252
<211> 880
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro368 (FL aFOLR1 wt22.4 MMP9 接头)
<400> 252
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Pro
485 490 495
Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr
500 505 510
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
515 520 525
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
530 535 540
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr
545 550 555 560
Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
565 570 575
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
580 585 590
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
595 600 605
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
610 615 620
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
625 630 635 640
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
645 650 655
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
660 665 670
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
675 680 685
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
690 695 700
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
705 710 715 720
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
725 730 735
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
740 745 750
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
755 760 765
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
770 775 780
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
785 790 795 800
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
805 810 815
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
820 825 830
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
835 840 845
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
850 855 860
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
865 870 875 880
<210> 253
<211> 881
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro369 (FL aFOLR1 wt22.4 KLK7.6 接头)
<400> 253
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly
485 490 495
Gln Asn Pro Tyr Ser Ala Gly Arg Gly Gly Gly Ser Gln Thr Val Val
500 505 510
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
515 520 525
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
530 535 540
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
545 550 555 560
Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
565 570 575
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
580 585 590
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
595 600 605
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
610 615 620
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
625 630 635 640
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
645 650 655
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
660 665 670
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
675 680 685
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
690 695 700
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
705 710 715 720
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
725 730 735
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
740 745 750
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
755 760 765
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
770 775 780
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
785 790 795 800
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
805 810 815
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
820 825 830
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
835 840 845
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
850 855 860
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
865 870 875 880
His
<210> 254
<211> 881
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro370 (FL aFOLR1 wt22.4 KLK7.11 接头)
<400> 254
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly
485 490 495
Arg Asn Val Tyr Ser Ala Gly Gly Gly Ser Gly Gly Gln Thr Val Val
500 505 510
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
515 520 525
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
530 535 540
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
545 550 555 560
Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
565 570 575
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
580 585 590
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
595 600 605
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
610 615 620
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
625 630 635 640
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
645 650 655
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
660 665 670
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
675 680 685
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
690 695 700
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
705 710 715 720
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
725 730 735
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
740 745 750
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
755 760 765
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
770 775 780
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
785 790 795 800
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
805 810 815
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
820 825 830
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
835 840 845
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
850 855 860
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
865 870 875 880
His
<210> 255
<211> 881
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro371 (FL aFOLR1 wt22.4 NC 接头)
<400> 255
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
115 120 125
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
130 135 140
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn
145 150 155 160
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
165 170 175
Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys
180 185 190
Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu
195 200 205
Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val
210 215 220
Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp
225 230 235 240
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
245 250 255
Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro
260 265 270
Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr
275 280 285
Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro
290 295 300
Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala
305 310 315 320
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
325 330 335
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr
340 345 350
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Gln Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Ala Gly Gly Ser Leu Arg Leu Ser Cys Glu Ala Ser
385 390 395 400
Gly Thr Thr Phe Ser Arg Asp Val Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Leu Val Ala Ile Ile Ser Arg Gly Gly Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ala Lys Asn Thr Val Tyr Leu Gln Met Asn Ser Leu Ala Pro Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Asn Ala Asn Thr Ala Thr Trp Gly Arg Val
465 470 475 480
Phe Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
485 490 495
Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val
500 505 510
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
515 520 525
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
530 535 540
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly
545 550 555 560
Thr Lys Asp Asp Ala Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
565 570 575
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
580 585 590
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
595 600 605
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
610 615 620
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
625 630 635 640
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
645 650 655
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
660 665 670
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
675 680 685
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
690 695 700
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
705 710 715 720
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
725 730 735
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
740 745 750
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
755 760 765
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
770 775 780
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
785 790 795 800
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
805 810 815
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
820 825 830
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
835 840 845
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
850 855 860
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
865 870 875 880
His
<210> 256
<211> 505
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro372 (Pro51 aFOLR1 wt22.4)
<400> 256
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Ala Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Gly Thr Thr Phe Ser Arg Asp
20 25 30
Val Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Leu Val
35 40 45
Ala Ile Ile Ser Arg Gly Gly Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Ala Pro Glu Asp Thr Ala Val Tyr Tyr Cys Asn
85 90 95
Ala Asn Thr Ala Thr Trp Gly Arg Val Phe Trp Gly Gln Gly Thr Gln
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
115 120 125
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
130 135 140
Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile
145 150 155 160
Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg
165 170 175
Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val
180 185 190
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
195 200 205
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
210 215 220
Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
225 230 235 240
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Thr Val Val Thr Gln
260 265 270
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
275 280 285
Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
290 295 300
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys
305 310 315 320
Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
325 330 335
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
340 345 350
Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
355 360 365
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gly Gly Gly Ser
370 375 380
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
385 390 395 400
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
405 410 415
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
420 425 430
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
435 440 445
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
450 455 460
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
465 470 475 480
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
485 490 495
Val Ser Ser His His His His His His
500 505
<210> 257
<211> 895
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro373 (FL aB7H3 hF7 Meprin 接头)
<400> 257
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr
20 25 30
His Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ala Val Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Pro Ser Arg Arg Thr Phe His Thr Tyr His Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ala Val
420 425 430
Ile Asn Trp Ser Gly Gly Ser Thr Val Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Gly Ala Thr Thr Gln Arg Ala Thr Glu Ala Ser Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Gly Lys Lys
500 505 510
Leu Ala Asp Glu Pro Glu Gly Gly Ser Gln Thr Val Val Thr Gln Glu
515 520 525
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly
530 535 540
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
545 550 555 560
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp
565 570 575
Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly
580 585 590
Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala
595 600 605
Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly
610 615 620
Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu
625 630 635 640
Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser
645 650 655
Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala
660 665 670
Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala
675 680 685
Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp
690 695 700
Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr
705 710 715 720
Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr
725 730 735
Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp
740 745 750
Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly
755 760 765
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
770 775 780
Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly
785 790 795 800
Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly
805 810 815
Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr
820 825 830
Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
835 840 845
Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp
850 855 860
Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser
865 870 875 880
Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895
<210> 258
<211> 891
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro374 (FL aB7H3 hF12 Meprin 接头)
<400> 258
Gln Val Gln Leu Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr
20 25 30
Ser Met Ala Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val
35 40 45
Ala Ala Ile Asn Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Ala Gly Gly Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly
115 120 125
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
130 135 140
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
145 150 155 160
Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
165 170 175
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr Tyr Tyr
180 185 190
Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
195 200 205
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
210 215 220
Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr Ile Ser
225 230 235 240
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
245 250 255
Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
260 265 270
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala Ser Ser
275 280 285
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
290 295 300
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe Leu Val
305 310 315 320
Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala
325 330 335
Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr
340 345 350
Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys
355 360 365
Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu
370 375 380
Gln Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu
385 390 395 400
Ser Cys Glu Ala Ser Pro Arg Thr Phe Ser Thr Tyr Ser Met Ala Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Ser Phe Val Ala Ala Ile Asn
420 425 430
Trp Ser Gly Gly Asn Thr Ser Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn
450 455 460
Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala Gly Gly
465 470 475 480
Val Leu Ala His His Asn Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr
485 490 495
Leu Val Thr Val Ser Ser Ser Gly Gly Gly Lys Lys Leu Ala Asp Glu
500 505 510
Pro Glu Gly Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
515 520 525
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
530 535 540
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
545 550 555 560
Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys
565 570 575
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
580 585 590
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
595 600 605
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
610 615 620
Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
625 630 635 640
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
645 650 655
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val
660 665 670
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
675 680 685
Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp
690 695 700
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
705 710 715 720
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
725 730 735
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
740 745 750
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
755 760 765
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
770 775 780
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
785 790 795 800
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
805 810 815
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
820 825 830
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
835 840 845
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
850 855 860
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
865 870 875 880
Val Thr Val Ser Ser His His His His His His
885 890
<210> 259
<211> 898
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro375 (FL hEGFR1/hEGFR2 Meprin 接头)
<400> 259
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Ala Ser Gly Arg Thr Phe Ser Ser Tyr Ala Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Val Ala
420 425 430
Ile Asn Trp Ser Ser Gly Ser Thr Tyr Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln
450 455 460
Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Ala Ala
465 470 475 480
Gly Tyr Gln Ile Asn Ser Gly Asn Tyr Asn Phe Lys Asp Tyr Glu Tyr
485 490 495
Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly
500 505 510
Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Ser Gln Thr Val Val
515 520 525
Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu
530 535 540
Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn
545 550 555 560
Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp
565 570 575
Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser
580 585 590
Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu
595 600 605
Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val
610 615 620
Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly
625 630 635 640
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
645 650 655
Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn
660 665 670
Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
675 680 685
Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp
690 695 700
Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser
705 710 715 720
Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr
725 730 735
Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile
740 745 750
Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
755 760 765
Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
770 775 780
Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala
785 790 795 800
Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln
805 810 815
Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly
820 825 830
Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser
835 840 845
Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg
850 855 860
Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser
865 870 875 880
Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His
885 890 895
His His
<210> 260
<211> 902
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro376 (Pro262 Meprin 接头)
<400> 260
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
275 280 285
Thr Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly
290 295 300
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
305 310 315 320
Leu Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe
325 330 335
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
340 345 350
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn
355 360 365
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
370 375 380
Ser Gly Gly Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser
385 390 395 400
Val Gln Thr Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg
405 410 415
Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys
420 425 430
Glu Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly
435 440 445
Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala
450 455 460
Lys Asn Thr Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr
465 470 475 480
Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr
485 490 495
Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser
500 505 510
Ser Ser Gly Gly Gly Lys Lys Leu Ala Asp Glu Pro Glu Gly Gly Ser
515 520 525
Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly
530 535 540
Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly
545 550 555 560
Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly
565 570 575
Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg
580 585 590
Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly
595 600 605
Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser
610 615 620
Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly
625 630 635 640
Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly
645 650 655
Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly
660 665 670
Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly
675 680 685
Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys
690 695 700
Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser
705 710 715 720
Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys
725 730 735
Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly
740 745 750
Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val
755 760 765
Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
770 775 780
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg
785 790 795 800
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser
805 810 815
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile
820 825 830
Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg
835 840 845
Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met
850 855 860
Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly
865 870 875 880
Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser
885 890 895
His His His His His His
900
<210> 261
<211> 877
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro390 (FL aFOLR1 h59.3延长的中心
接头 MMP9 接头)
<400> 261
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro
385 390 395 400
Gly Asn Thr Phe Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln
465 470 475 480
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
485 490 495
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
500 505 510
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
515 520 525
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
530 535 540
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
545 550 555 560
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
565 570 575
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
580 585 590
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
595 600 605
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
610 615 620
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
625 630 635 640
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
645 650 655
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
660 665 670
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
675 680 685
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
690 695 700
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
705 710 715 720
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
725 730 735
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
740 745 750
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
755 760 765
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
770 775 780
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
785 790 795 800
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
805 810 815
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
820 825 830
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
835 840 845
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
850 855 860
Thr Leu Val Thr Val Ser Ser His His His His His His
865 870 875
<210> 262
<211> 881
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro391 (FL aFOLR1 h59.3延长的中心
接头和延长的MMP9 接头)
<400> 262
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Pro Gly Asn Thr Phe Ser Ile Ser
20 25 30
Ala Met Gly Trp Tyr Arg Gln Ala Pro Gly Lys Gln Arg Glu Trp Val
35 40 45
Ala Val Thr His Ser Asp Tyr Ser Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys Lys
85 90 95
His Tyr Gly Ile Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
115 120 125
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
130 135 140
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln
145 150 155 160
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
165 170 175
Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr
180 185 190
Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn
195 200 205
Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn
210 215 220
Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr
225 230 235 240
Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr
245 250 255
Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val
260 265 270
Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr
275 280 285
Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile
290 295 300
Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly
305 310 315 320
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
325 330 335
Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp
340 345 350
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
355 360 365
Gly Gly Ser Gly Gly Gly Ser Gln Val Gln Leu Val Glu Ser Gly Gly
370 375 380
Gly Leu Val Gln Pro Gly Gly Ser Leu Arg Leu Ser Cys Ala Ala Pro
385 390 395 400
Gly Asn Thr Phe Ser Ile Ser Ala Met Gly Trp Tyr Arg Gln Ala Pro
405 410 415
Gly Lys Gln Arg Glu Trp Val Ala Val Thr His Ser Asp Tyr Ser Thr
420 425 430
Asn Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn
435 440 445
Ser Lys Asn Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp
450 455 460
Thr Ala Val Tyr Tyr Cys Lys His Tyr Gly Ile Asp Tyr Trp Gly Gln
465 470 475 480
Gly Thr Leu Val Thr Val Ser Ser Ser Gly Gly Pro Gly Pro Ala Gly
485 490 495
Met Lys Gly Leu Pro Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr
500 505 510
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
515 520 525
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
530 535 540
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
545 550 555 560
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
565 570 575
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
580 585 590
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
595 600 605
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
610 615 620
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
625 630 635 640
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
645 650 655
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
660 665 670
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
675 680 685
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
690 695 700
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
705 710 715 720
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
725 730 735
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
740 745 750
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
755 760 765
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
770 775 780
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
785 790 795 800
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
805 810 815
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
820 825 830
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
835 840 845
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
850 855 860
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
865 870 875 880
His
<210> 263
<211> 897
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro412 (具有2aa延长的中心
接头的Pro186)
<400> 263
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
370 375 380
Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser
385 390 395 400
Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly
405 410 415
Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser
420 425 430
Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys
435 440 445
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu
450 455 460
Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala
465 470 475 480
Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr
485 490 495
Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Ser Gly Gly Pro
500 505 510
Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr
515 520 525
Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr
530 535 540
Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp
545 550 555 560
Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr
565 570 575
Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu
580 585 590
Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp
595 600 605
Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe
610 615 620
Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly
625 630 635 640
Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
645 650 655
Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys
660 665 670
Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
675 680 685
Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys
690 695 700
Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys
705 710 715 720
Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala
725 730 735
Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser
740 745 750
Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
755 760 765
Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly
770 775 780
Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala
785 790 795 800
Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala
805 810 815
Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg
820 825 830
Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg
835 840 845
Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro
850 855 860
Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val
865 870 875 880
Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His
885 890 895
His
<210> 264
<211> 899
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro413 (具有4aa延长的中心
接头的Pro186)
<400> 264
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Ser Gly Gly Gly Ser Gly Gly Gly Ser
370 375 380
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
385 390 395 400
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
405 410 415
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
420 425 430
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
435 440 445
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
450 455 460
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
465 470 475 480
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
485 490 495
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Ser Gly
500 505 510
Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln Thr Val
515 520 525
Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr
530 535 540
Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro
545 550 555 560
Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly
565 570 575
Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly
580 585 590
Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro
595 600 605
Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp
610 615 620
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly
625 630 635 640
Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln
645 650 655
Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
660 665 670
Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
675 680 685
Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp
690 695 700
Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
705 710 715 720
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
725 730 735
Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr
740 745 750
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
770 775 780
Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys
785 790 795 800
Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg
805 810 815
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser
820 825 830
Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile
835 840 845
Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu
850 855 860
Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu
865 870 875 880
Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His
885 890 895
His His His
<210> 265
<211> 901
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro414 (具有6aa延长的中心
接头的Pro186)
<400> 265
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly Gly Ser Gly Gly Gly
370 375 380
Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly
385 390 395 400
Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser
405 410 415
Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe
420 425 430
Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser
435 440 445
Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val
450 455 460
Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr
465 470 475 480
Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr
485 490 495
Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly
500 505 510
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
515 520 525
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
530 535 540
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
545 550 555 560
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
565 570 575
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
580 585 590
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
595 600 605
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
610 615 620
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
625 630 635 640
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
645 650 655
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
660 665 670
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
675 680 685
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
690 695 700
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
705 710 715 720
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
725 730 735
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
740 745 750
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
755 760 765
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
770 775 780
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
785 790 795 800
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
805 810 815
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
820 825 830
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
835 840 845
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
850 855 860
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
865 870 875 880
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
885 890 895
His His His His His
900
<210> 266
<211> 903
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro415 (具有8aa延长的中心
接头的Pro186)
<400> 266
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gly Gly
370 375 380
Gly Ser Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr
385 390 395 400
Gly Gly Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg
405 410 415
Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu
420 425 430
Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp
435 440 445
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr
450 455 460
Val Asp Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr
465 470 475 480
Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu
485 490 495
Tyr Asp Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly
500 505 510
Gly Gly Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly
515 520 525
Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly
530 535 540
Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser
545 550 555 560
Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg
565 570 575
Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala
580 585 590
Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser
595 600 605
Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr
610 615 620
Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly
625 630 635 640
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
645 650 655
Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser
660 665 670
Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro
675 680 685
Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr
690 695 700
Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile
705 710 715 720
Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu
725 730 735
Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe
740 745 750
Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu
755 760 765
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val
770 775 780
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu
785 790 795 800
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met
805 810 815
Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser
820 825 830
Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly
835 840 845
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln
850 855 860
Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile
865 870 875 880
Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser
885 890 895
Ser His His His His His His
900
<210> 267
<211> 893
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro416 (具有2aa缩短的中心
接头的Pro186)
<400> 267
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Ser Gly Gly Gly Ser Gln Val Lys
370 375 380
Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu Arg
385 390 395 400
Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly
405 410 415
Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile
420 425 430
Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg
435 440 445
Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln Met
450 455 460
Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala Ala
465 470 475 480
Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly
485 490 495
Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Pro Gly Pro Ala Gly
500 505 510
Met Lys Gly Leu Pro Gly Ser Gln Thr Val Val Thr Gln Glu Pro Ser
515 520 525
Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser
530 535 540
Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys
545 550 555 560
Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp
565 570 575
Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys
580 585 590
Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr
595 600 605
Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr
610 615 620
Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln
625 630 635 640
Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys
645 650 655
Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn
660 665 670
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile
675 680 685
Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val
690 695 700
Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr
705 710 715 720
Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys
725 730 735
Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr
740 745 750
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser
755 760 765
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
770 775 780
Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr
785 790 795 800
Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly
805 810 815
Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr
820 825 830
Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
835 840 845
Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala
850 855 860
Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly
865 870 875 880
Thr Leu Val Thr Val Ser Ser His His His His His His
885 890
<210> 268
<211> 891
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro417 (具有4aa缩短的中心
接头的Pro186)
<400> 268
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Ser Gly Gly Gly Ser Gln Val Lys Leu
370 375 380
Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu Arg Leu
385 390 395 400
Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp
405 410 415
Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser
420 425 430
Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe
435 440 445
Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln Met Asn
450 455 460
Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala
465 470 475 480
Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln
485 490 495
Gly Thr Gln Val Thr Val Ser Ser Ser Gly Pro Gly Pro Ala Gly Met
500 505 510
Lys Gly Leu Pro Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr
515 520 525
Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly
530 535 540
Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly
545 550 555 560
Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys
565 570 575
Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala
580 585 590
Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys
595 600 605
Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu
610 615 620
Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val
625 630 635 640
Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser
645 650 655
Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val
660 665 670
Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser
675 680 685
Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp
690 695 700
Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln
705 710 715 720
Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg
725 730 735
His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly
740 745 750
Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly
755 760 765
Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro
770 775 780
Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser
785 790 795 800
Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu
805 810 815
Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu
820 825 830
Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr
835 840 845
Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr
850 855 860
Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu
865 870 875 880
Val Thr Val Ser Ser His His His His His His
885 890
<210> 269
<211> 889
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro418 (具有6aa缩短的中心
接头的Pro186)
<400> 269
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Gly Ser Gln Val Lys Leu Glu
370 375 380
Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu Arg Leu Thr
385 390 395 400
Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met Gly Trp Phe
405 410 415
Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly Ile Ser Trp
420 425 430
Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly Arg Phe Thr
435 440 445
Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln Met Asn Ser
450 455 460
Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala Ala Ala Gly
465 470 475 480
Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly
485 490 495
Thr Gln Val Thr Val Ser Ser Gly Pro Gly Pro Ala Gly Met Lys Gly
500 505 510
Leu Pro Ser Gln Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser
515 520 525
Pro Gly Gly Thr Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val
530 535 540
Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala
545 550 555 560
Pro Arg Gly Leu Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr
565 570 575
Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr
580 585 590
Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu
595 600 605
Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val
610 615 620
Leu Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser
625 630 635 640
Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala
645 650 655
Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln
660 665 670
Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr
675 680 685
Asp Tyr Lys Asp Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe
690 695 700
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
705 710 715 720
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly
725 730 735
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
740 745 750
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser
755 760 765
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn
770 775 780
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe
785 790 795 800
Gly Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
805 810 815
Ser Ser Ile Ser Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val
820 825 830
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr
835 840 845
Leu Gln Met Asn Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys
850 855 860
Thr Ile Gly Gly Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr
865 870 875 880
Val Ser Ser His His His His His His
885
<210> 270
<211> 885
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro420 (FL aFOLR1 h77.2/haEGFR1
异质COBRA MMP9 接头)
<400> 270
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser
20 25 30
Val Met Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val
35 40 45
Ala Ile Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys
50 55 60
Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu
65 70 75 80
Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn
85 90 95
Arg Asn Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val
100 105 110
Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu
115 120 125
Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys
130 135 140
Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg
145 150 155 160
Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys
165 170 175
Tyr Asn Asn Tyr Ala Thr Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe
180 185 190
Thr Ile Ser Arg Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn
195 200 205
Asn Leu Lys Thr Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Ala
210 215 220
Asn Phe Gly Asn Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly
225 230 235 240
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln
245 250 255
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
260 265 270
Val Thr Leu Thr Cys Ala Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
275 280 285
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
290 295 300
Ile Gly Gly Thr Lys Phe Leu Val Pro Gly Thr Pro Ala Arg Phe Ser
305 310 315 320
Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln
325 330 335
Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg
340 345 350
Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser
355 360 365
Gly Gly Gly Ser Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val
370 375 380
Arg Pro Gly Gly Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr
385 390 395 400
Ser Arg Ser Tyr Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu
405 410 415
Arg Glu Phe Val Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr
420 425 430
Ala Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys
435 440 445
Asn Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala
450 455 460
Leu Tyr Tyr Cys Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu
465 470 475 480
Tyr Glu Tyr Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490 495
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
500 505 510
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
515 520 525
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
530 535 540
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
545 550 555 560
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
565 570 575
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
580 585 590
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
595 600 605
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
610 615 620
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
625 630 635 640
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
645 650 655
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
660 665 670
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
675 680 685
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
690 695 700
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
705 710 715 720
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
725 730 735
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
740 745 750
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
755 760 765
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
770 775 780
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
785 790 795 800
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
805 810 815
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
820 825 830
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
835 840 845
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
850 855 860
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
865 870 875 880
His His His His His
885
<210> 271
<211> 885
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro421 (FL haEGFR1/aFOLR1 h77.2
异质COBRA MMP9 接头)
<400> 271
Gln Val Lys Leu Val Glu Ser Gly Gly Gly Val Val Arg Pro Gly Gly
1 5 10 15
Ser Leu Thr Leu Ser Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Leu Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly Ser Leu
385 390 395 400
Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Ser Asn Ser Val Met
405 410 415
Ala Trp Tyr Arg Gln Thr Pro Gly Asn Glu Arg Glu Phe Val Ala Ile
420 425 430
Ile Asn Ser Ile Gly Ile Thr Asn Tyr Ala Asp Ser Val Lys Gly Arg
435 440 445
Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr Leu Gln Met
450 455 460
Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Val Cys Asn Arg Asn
465 470 475 480
Phe Asp Arg Ile Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490 495
Ser Gly Gly Pro Gly Pro Ala Gly Met Lys Gly Leu Pro Gly Ser Gln
500 505 510
Thr Val Val Thr Gln Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr
515 520 525
Val Thr Leu Thr Cys Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn
530 535 540
Tyr Pro Asn Trp Val Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu
545 550 555 560
Ile Gly Asp Tyr Lys Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe
565 570 575
Ser Gly Ser Leu Leu Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val
580 585 590
Gln Pro Glu Asp Glu Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn
595 600 605
Arg Trp Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly
610 615 620
Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu
625 630 635 640
Val Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe
645 650 655
Thr Phe Asn Lys Tyr Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys
660 665 670
Gly Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp
675 680 685
Asp Asp Asp Lys Ala Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg
690 695 700
Asp Asp Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr
705 710 715 720
Glu Asp Thr Ala Val Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn
725 730 735
Ser Tyr Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr
740 745 750
Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu
755 760 765
Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu
770 775 780
Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp
785 790 795 800
Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser
805 810 815
Gly Ser Gly Arg Asp Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe
820 825 830
Thr Ile Ser Arg Asp Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn
835 840 845
Ser Leu Arg Pro Glu Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly
850 855 860
Ser Leu Ser Val Ser Ser Gln Gly Thr Leu Val Thr Val Ser Ser His
865 870 875 880
His His His His His
885
<210> 272
<211> 896
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<223> 合成构建体 - Pro429 (Pro186 Meprin/颗粒酶B接头)
<400> 272
Gln Val Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly
1 5 10 15
Ser Leu Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr
20 25 30
Gly Met Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val
35 40 45
Ser Gly Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp
65 70 75 80
Leu Gln Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Ala Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp
100 105 110
Tyr Trp Gly Gln Gly Thr Gln Val Thr Val Ser Ser Gly Gly Gly Ser
115 120 125
Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val
130 135 140
Gln Pro Gly Gly Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr
145 150 155 160
Phe Asn Lys Tyr Ala Ile Asn Trp Val Arg Gln Ala Pro Gly Lys Gly
165 170 175
Leu Glu Trp Val Ala Arg Ile Arg Ser Lys Tyr Asn Asn Tyr Ala Thr
180 185 190
Tyr Tyr Ala Asp Gln Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp
195 200 205
Ser Lys Asn Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp
210 215 220
Thr Ala Val Tyr Tyr Cys Val Arg His Ala Asn Phe Gly Asn Ser Tyr
225 230 235 240
Ile Ser Tyr Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
245 250 255
Ser Gly Gly Gly Ser Gly Gly Gly Ser Gln Thr Val Val Thr Gln Glu
260 265 270
Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys Ala
275 280 285
Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val Gln
290 295 300
Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Gly Thr Lys Phe
305 310 315 320
Leu Val Pro Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu Gly Gly
325 330 335
Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu Ala Glu
340 345 350
Tyr Tyr Cys Thr Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly Gly Gly
355 360 365
Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser Gln Val
370 375 380
Lys Leu Glu Glu Ser Gly Gly Gly Ser Val Gln Thr Gly Gly Ser Leu
385 390 395 400
Arg Leu Thr Cys Ala Ala Ser Gly Arg Thr Ser Arg Ser Tyr Gly Met
405 410 415
Gly Trp Phe Arg Gln Ala Pro Gly Lys Glu Arg Glu Phe Val Ser Gly
420 425 430
Ile Ser Trp Arg Gly Asp Ser Thr Gly Tyr Ala Asp Ser Val Lys Gly
435 440 445
Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Thr Val Asp Leu Gln
450 455 460
Met Asn Ser Leu Lys Pro Glu Asp Thr Ala Ile Tyr Tyr Cys Ala Ala
465 470 475 480
Ala Ala Gly Ser Ala Trp Tyr Gly Thr Leu Tyr Glu Tyr Asp Tyr Trp
485 490 495
Gly Gln Gly Thr Gln Val Thr Val Ser Ser Ser Gly Gly Gly Val Tyr
500 505 510
Ala Asp Ser Leu Glu Asp Gly Gly Gly Ser Gln Thr Val Val Thr Gln
515 520 525
Glu Pro Ser Leu Thr Val Ser Pro Gly Gly Thr Val Thr Leu Thr Cys
530 535 540
Gly Ser Ser Thr Gly Ala Val Thr Ser Gly Asn Tyr Pro Asn Trp Val
545 550 555 560
Gln Gln Lys Pro Gly Gln Ala Pro Arg Gly Leu Ile Gly Asp Tyr Lys
565 570 575
Asp Asp Asp Asp Lys Gly Thr Pro Ala Arg Phe Ser Gly Ser Leu Leu
580 585 590
Gly Gly Lys Ala Ala Leu Thr Leu Ser Gly Val Gln Pro Glu Asp Glu
595 600 605
Ala Glu Tyr Tyr Cys Val Leu Trp Tyr Ser Asn Arg Trp Val Phe Gly
610 615 620
Gly Gly Thr Lys Leu Thr Val Leu Gly Gly Gly Ser Gly Gly Gly Ser
625 630 635 640
Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
645 650 655
Ser Leu Lys Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Asn Lys Tyr
660 665 670
Ala Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
675 680 685
Ala Arg Ile Arg Ser Lys Tyr Asp Tyr Lys Asp Asp Asp Asp Lys Ala
690 695 700
Asp Ser Val Lys Asp Arg Phe Thr Ile Ser Arg Asp Asp Ser Lys Asn
705 710 715 720
Thr Ala Tyr Leu Gln Met Asn Asn Leu Lys Thr Glu Asp Thr Ala Val
725 730 735
Tyr Tyr Cys Val Arg His Gly Asn Phe Gly Asn Ser Tyr Ile Ser Tyr
740 745 750
Trp Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly Gly
755 760 765
Gly Gly Ser Gly Gly Gly Ser Glu Val Gln Leu Val Glu Ser Gly Gly
770 775 780
Gly Leu Val Gln Pro Gly Asn Ser Leu Arg Leu Ser Cys Ala Ala Ser
785 790 795 800
Gly Phe Thr Phe Ser Lys Phe Gly Met Ser Trp Val Arg Gln Ala Pro
805 810 815
Gly Lys Gly Leu Glu Trp Val Ser Ser Ile Ser Gly Ser Gly Arg Asp
820 825 830
Thr Leu Tyr Ala Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp
835 840 845
Asn Ala Lys Thr Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Pro Glu
850 855 860
Asp Thr Ala Val Tyr Tyr Cys Thr Ile Gly Gly Ser Leu Ser Val Ser
865 870 875 880
Ser Gln Gly Thr Leu Val Thr Val Ser Ser His His His His His His
885 890 895

Claims (49)

1.一种蛋白质，所述蛋白质从N-末端至C-末端包含：
a)结合至人肿瘤靶抗原(TTA)的第一单结构域抗原结合结构域(sdABD)(sdABD-TTA)；
b)第一结构域接头；
c)受约束的Fv结构域，所述受约束的Fv结构域包含：
i)包含vhCDR1、vhCDR2和vhCDR3的第一可变重结构域；
ii)受约束的不可裂解的接头(CNCL)；以及
iii)包含vlCDR1、vlCDR2和vlCDR3的第一可变轻结构域；
d)第二结构域接头；
e)第二sdABD-TTA；
f)可裂解的接头(CL)；
g)受约束的伪Fv结构域，所述受约束的伪Fv结构域包含：
i)第一伪轻可变结构域；
ii)不可裂解的接头(NCL)；以及
iii)第一伪重可变结构域；
h)第三结构域接头；以及
i)结合至人血清白蛋白的第三sdABD；
其中所述第一可变重结构域和所述第一可变轻结构域能够结合人CD3，但所述受约束的Fv结构域不结合CD3；其中所述第一可变重结构域和所述第一伪可变轻结构域分子内缔合以形成无活性的Fv；并且其中所述第一可变轻结构域和所述第一伪可变重结构域分子内缔合以形成无活性的Fv。
2.一种蛋白质，所述蛋白质从N-末端至C-末端包含：
a)第一sdABD-TTA；
b)第一结构域接头；
c)受约束的Fv结构域，所述受约束的Fv结构域包含：
i)包含vhCDR1、vhCDR2和vhCDR3的第一可变重结构域；
ii)受约束的可裂解的接头(CCL)；以及
iii)包含vlCDR1、vlCDR2和vlCDR3的第一可变轻结构域；
d)第二结构域接头；
e)第二sdABD-TTA；
f)可裂解的接头(CL)；
g)受约束的伪Fv结构域，所述受约束的伪Fv结构域包含：
i)第一伪重可变结构域；
ii)不可裂解的接头(NCL)；以及
iii)第一伪轻可变结构域；
h)第三结构域接头；以及
i)结合至人血清白蛋白的第三sdABD；
其中所述第一可变重结构域和所述第一可变轻结构域能够结合人CD3，但所述受约束的Fv结构域不结合CD3；其中所述第一可变重结构域和所述第一伪可变轻结构域分子内缔合以形成无活性的Fv；并且其中所述第一可变轻结构域和所述第一伪可变重结构域分子内缔合以形成无活性的Fv。
3.根据权利要求1至2中任一项所述的蛋白质，其中所述第一可变重结构域在所述第一可变轻结构域的N-末端，并且所述伪轻可变结构域在所述伪可变重结构域的N-末端。
4.根据权利要求1至2中任一项所述的蛋白质，其中所述第一可变重结构域在所述第一可变轻结构域的N-末端，并且所述伪可变重结构域在所述伪可变轻结构域的N-末端。
5.根据权利要求1至2中任一项所述的蛋白质，其中所述第一可变轻结构域在所述第一可变重结构域的N-末端，并且所述伪轻可变结构域在所述伪可变重结构域的N-末端。
6.根据权利要求1至2中任一项所述的蛋白质，其中所述第一可变轻结构域在所述第一可变重结构域的N-末端，并且所述伪可变重结构域在所述伪可变轻结构域的N-末端。
7.根据权利要求1-6中任一项所述的蛋白质，其中所述第一TTA和所述第二TTA是相同的。
8.根据权利要求1-6中任一项所述的蛋白质，其中所述第一TTA和所述第二TTA是不同的。
9.根据权利要求1-8中任一项所述的蛋白质，其中所述第一TTA和所述第二TTA选自EGFR、EpCAM、FOLR1和B7H3。
10.根据权利要求1-9中任一项所述的蛋白质，其中所述第一sdABD-TTA和所述第二sdABD-TTA选自由以下组成的组：SEQ ID NO:1、SEQ ID NO:5、SEQ ID NO:9、SEQ ID NO:13、SEQ ID NO:17、SEQ ID NO:21、SEQ ID NO:25、SEQ ID NO:29、SEQ ID NO:33、SEQ ID NO:37以及SEQ ID NO:41。
11.根据权利要求1至10所述的蛋白质，其中所述半衰期延长结构域具有SEQ ID NO:45。
12.根据权利要求1至11所述的蛋白质，其中所述可裂解的接头被选自由以下组成的组的人蛋白酶裂解：MMP2、MMP9、穿膜肽酶A、穿膜肽酶B、组织蛋白酶S、组织蛋白酶K、组织蛋白酶L、颗粒酶B、uPA、激肽释放酶7、蛋白裂解酶和凝血酶。
13.根据权利要求1所述的蛋白质，所述蛋白质包括选自由以下组成的组的蛋白质：Pro186、Pro225、Pro226、Pro233、Pro311、Pro312、Pro313、Pro495、Pro246、Pro254、Pro255、Pro256、Pro420、Pro421、Pro432、Pro479、Pro480、Pro187、Pro221、Pro222、Pro223、Pro224、Pro393、Pro394、Pro395、Pro396、Pro429、Pro430以及Pro431。
14.一种核酸，所述核酸编码根据权利要求1至13中任一项所述的蛋白质。
15.一种表达载体，所述表达载体包含如权利要求14所述的核酸。
16.一种宿主细胞，所述宿主细胞包含如权利要求15所述的表达载体。
17.一种制备蛋白质的方法，所述方法包括在所述蛋白质被表达的条件下培养如权利要求16所述的宿主细胞以及回收所述蛋白质。
18.一种治疗癌症的方法，所述方法包括向患者施用如权利要求1至13中任一项所述的蛋白质。
19.一种组合物，所述组合物包含：
a)第一蛋白质，所述第一蛋白质从N-末端至C-末端包含：
i)第一sdABD-TTA；
ii)第一结构域接头；
iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：
1)包含vhCDR1、vhCDR2和vhCDR3的可变重链；
2)可裂解的接头；以及
3)包含iVLCDR1、iVLCDR2和iVLCDR3的第一伪可变轻结构域；
iv)第二结构域接头；
v)结合至人血清白蛋白的第一sdABD；
a)第二蛋白质，所述第二蛋白质从N-末端至C-末端包含：
i)结合至人肿瘤靶抗原的第三sdABD；
ii)第三结构域接头；
iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：
1)包含VLCDR1、VLCDR2和VLCDR3的可变轻链；
2)可裂解的接头；以及
3)包含iVHCDR1、iVHCDR2和iVHCDR3的第一伪可变重结构域；
iv)第四结构域接头；
v)结合至人血清白蛋白的第四sdABD；
其中
所述第一可变重结构域和所述第一可变轻结构域能够在缔合时结合人CD3；
所述第一可变重结构域和所述第一伪可变轻结构域分子间缔合以形成无活性的Fv；
所述第一可变轻结构域和所述第一伪可变重结构域分子间缔合以形成无活性的Fv；
其中所述第一sdABD和所述第三sdABD选自由以下组成的组：SEQ ID NO:1、SEQ ID NO:5、SEQ ID NO:9、SEQ ID NO:13、SEQ ID NO:17、SEQ ID NO:21、SEQ ID NO:25、SEQ ID NO:29、SEQ ID NO:33、SEQ ID NO:37以及SEQ ID NO:41。
20.根据权利要求19所述的蛋白质，其中所述第一TTA和所述第二TTA是相同的。
21.根据权利要求19所述的蛋白质，其中所述第一TTA和所述第二TTA是不同的。
22.根据权利要求19至21中任一项所述的蛋白质，其中所述第三sdABD和所述第四sdABD具有SEQ ID NO:45。
23.一种核酸组合物，所述核酸组合物包含：
a)编码根据权利要求19至22中任一项所述的第一蛋白质的第一核酸；以及
b)编码根据权利要求19至22中任一项所述的第二蛋白质的第二核酸。
24.一种表达载体组合物，所述表达载体组合物包含：
a)第一表达载体，所述第一表达载体包含如权利要求23所述的第一核酸；以及
b)第二表达载体，所述第二表达载体包含如权利要求23所述的第二核酸。
25.一种宿主细胞，所述宿主细胞包含如权利要求24所述的表达载体组合物。
26.一种制备组合物的方法，所述方法包括在所述蛋白质被表达的条件下培养如权利要求25所述的宿主细胞以及回收所述蛋白质。
27.一种治疗癌症的方法，所述方法包括向患者施用如权利要求19至22中任一项所述的蛋白质。
28.一种组合物，所述组合物包含：
a)第一蛋白质，所述第一蛋白质从N-末端至C-末端包含：
i)第一sdABD-TTA；
ii)第一结构域接头；
iii)第二sdABD-TTA；
iv)第二结构域接头；
iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：
1)包含vhCDR1、vhCDR2和vhCDR3的可变重链；
2)可裂解的接头；以及
3)包含iVLCDR1、iVLCDR2和iVLCDR3的第一伪可变轻结构域；
iv)第三结构域接头；以及
v)sdABD-HSA；
a)第二蛋白质，所述第二蛋白质从N-末端至C-末端包含：
i)第三sdABD-TTA；
ii)第四结构域接头；
iii)第四sdABD-TTA；
iv)第五结构域接头；
iii)伪Fv结构域，所述伪Fv结构域从N-末端至C-末端包含：
1)包含VLCDR1、VLCDR2和VLCDR3的可变轻链；
2)可裂解的接头；以及
3)包含iVHCDR1、iVHCDR2和iVHCDR3的第一伪可变重结构域；
iv)第六结构域接头；
v)sdABD-HSA；
其中
所述第一可变重结构域和所述第一可变轻结构域能够在缔合时结合人CD3；
所述第一可变重结构域和所述第一伪可变轻结构域分子间缔合以形成无活性的Fv；
所述第一可变轻结构域和所述第一伪可变重结构域分子间缔合以形成无活性的Fv。
29.根据权利要求28所述的组合物，其中所述sdABD-HSA具有SEQ ID NO:45。
30.一种核酸组合物，所述核酸组合物包含：
a)编码根据权利要求28至29中任一项所述的第一蛋白质的第一核酸；以及
b)编码根据权利要求28至29中任一项所述的第二蛋白质的第二核酸。
31.一种表达载体组合物，所述表达载体组合物包含：
a)第一表达载体，所述第一表达载体包含如权利要求30所述的第一核酸；以及
b)第二表达载体，所述第二表达载体包含如权利要求30所述的第二核酸。
32.一种宿主细胞，所述宿主细胞包含如权利要求31所述的表达载体组合物。
33.一种制备组合物的方法，所述方法包括在所述蛋白质被表达的条件下培养如权利要求32所述的宿主细胞以及回收所述蛋白质。
34.一种治疗癌症的方法，所述方法包括向患者施用如权利要求28至29中任一项所述的蛋白质。
35.一种蛋白质，所述蛋白质从N-末端至C-末端包含：
a)结合至人肿瘤靶抗原(TTA)的单结构域抗原结合结构域(sdABD)(sdABD-TTA)；
b)第一结构域接头；
c)受约束的Fv结构域，所述受约束的Fv结构域包含：
i)包含vhCDR1、vhCDR2和vhCDR3的第一可变重结构域；
ii)受约束的不可裂解的接头(CNCL)；以及
iii)包含vlCDR1、vlCDR2和vlCDR3的第一可变轻结构域；
d)可裂解的接头(CL)；
e)结合至人血清白蛋白的第二sdABD；
f)结构域接头；
g)受约束的伪Fv结构域，所述受约束的伪Fv结构域包含：
i)第一伪轻可变结构域；
ii)不可裂解的接头(NCL)；以及
iii)第一伪重可变结构域；
其中所述第一可变重结构域和所述第一可变轻结构域能够结合人CD3，但所述受约束的Fv结构域不结合CD3；
所述第一可变重结构域和所述第一伪可变轻结构域分子内缔合以形成无活性的Fv；并且
所述第一可变轻结构域和所述第一伪可变重结构域分子内缔合以形成无活性的Fv。
36.根据权利要求35所述的蛋白质，其中所述第一可变重结构域在所述第一可变轻结构域的N-末端，并且所述伪轻可变结构域在所述伪可变重结构域的N-末端。
37.根据权利要求35所述的蛋白质，其中所述第一可变重结构域在所述第一可变轻结构域的N-末端，并且所述伪可变重结构域在所述伪可变轻结构域的N-末端。
38.根据权利要求35所述的蛋白质，其中所述第一可变轻结构域在所述第一可变重结构域的N-末端，并且所述伪轻可变结构域在所述伪可变重结构域的N-末端。
39.根据权利要求35所述的蛋白质，其中所述第一可变轻结构域在所述第一可变重结构域的N-末端，并且所述伪可变重结构域在所述伪可变轻结构域的N-末端。
40.根据权利要求35至39所述的蛋白质，其中所述TTA选自EGFR、EpCAM、FOLR1和B7H3。
41.根据权利要求35至40中任一项所述的蛋白质，其中所述sdABD-TTA选自由以下组成的组：SEQ ID NO:1、SEQ ID NO:5、SEQ ID NO:9、SEQ ID NO:13、SEQ ID NO:17、SEQ ID NO:21、SEQ ID NO:25、SEQ ID NO:29、SEQ ID NO:33、SEQ ID NO:37以及SEQ ID NO:41。
42.根据权利要求35至41中任一项所述的蛋白质，其中所述半衰期延长结构域具有SEQID NO:45。
43.根据权利要求35至42中任一项所述的蛋白质，其中所述可裂解的接头被选自由以下组成的组的人蛋白酶裂解：MMP2、MMP9、穿膜肽酶A、穿膜肽酶B、组织蛋白酶S、组织蛋白酶K、组织蛋白酶L、颗粒酶B、uPA、激肽释放酶7、蛋白裂解酶和凝血酶。
44.根据权利要求35所述的蛋白质，所述蛋白质包括Pro258、Pro356、Pro359、Pro388以及Pro364。
45.一种核酸，所述核酸编码根据权利要求35至44中任一项所述的蛋白质。
46.一种表达载体，所述表达载体包含如权利要求45所述的核酸。
47.一种宿主细胞，所述宿主细胞包含如权利要求46所述的表达载体。
48.一种制备蛋白质的方法，所述方法包括在所述蛋白质被表达的条件下培养如权利要求47所述的宿主细胞以及回收所述蛋白质。
49.一种治疗癌症的方法，所述方法包括向患者施用如权利要求35至44中任一项所述的蛋白质。
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