CN117255691A - 干扰素前药、制备方法及应用 - Google Patents

干扰素前药、制备方法及应用 Download PDF

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CN117255691A
CN117255691A CN202280009981.9A CN202280009981A CN117255691A CN 117255691 A CN117255691 A CN 117255691A CN 202280009981 A CN202280009981 A CN 202280009981A CN 117255691 A CN117255691 A CN 117255691A
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吕越峰
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Askgene Pharma Inc
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Abstract

本发明提供干扰素前药和其制备方法及其在刺激免疫系统或治疗癌症或感染性疾病中的应用。

Description

干扰素前药、制备方法及应用
相关申请交叉引用
本申请要求于2021年1月14日提交的美国临时申请第63/137,370号的优先权，优先权申请的内容以全文引用的方式并入本文中。
序列表
本申请含有已经以ASCII格式电子提交的序列表，并且特此以全文引用的方式并入。创建于2022年1月13日的所述ASCII副本名称为025471_WO014_SL.txt且大小为397,253字节。
背景技术
干扰素(IFN)调控多种免疫功能，包括在病毒感染时调控及活化免疫反应。根据不同干扰素所传递信号的受体不同，干扰素可分为多个类型。I型干扰素和细胞表面上受体复合物结合，所述受体复合物也即由IFNAR1链和IFNAR2链构成的IFN-α/β受体(IFNAR)(Weerdet al.The Journal of Biological Chemistry(2007)282(28):20053–7)。II型干扰素(人干扰素γ，IFNγ)由细胞毒性T细胞和辅助型T细胞分泌、释放，并与由IFNGR1链和IFNGR2链构成的IFNγ受体(IFNGR)结合(Parkin and Cohen.Immunology(2001)357(9270):1777-89)。
干扰素-γ(IFNγ)和干扰素-α(IFNα)在调控免疫系统中起着重要作用。他们已在临床研究中被证实可用于治疗癌症。例如，IFNγ被证实可用于治疗卵巢癌(Marth etal.,Int.J.Gynecol.(Cancer)(2006)16:1522–1528)。在二期临床研究中，高达0.1mg的剂量被证明是有效的，然而，当剂量降低时，出现多种明显的副作用。IFNα-2b已被批准为一种治疗性蛋白，以单一疗法或者与其他抗肿瘤药物联合使用，可以治疗多种癌症，然而其应用中存在类似感冒的并发症限制了其临床应用(Kirwood.,Semin Oncol(2002)29(3Suppl 7):18-26)。
因此有必要开发一种基于IFNγ和IFNα的且具有更强的肿瘤位点特异性，更少的副作用，和/或增强的治疗效率的肿瘤治疗方法。本公开涉及到的所有文献、专利、专利申请在此均全文被引用。
发明概述
本发明提供一种前药，包括人干扰素(IFN)激动剂多肽，掩蔽部分和载体部分，其中所述掩蔽部分包括可以与人干扰素激动剂多肽结合并抑制所述人干扰素激动剂多肽生物学活性的抗体的抗原结合片段，所述人干扰素激动剂多肽为干扰素α(IFNα)且与所述载体部分融合，所述掩蔽部分与所述人干扰素激动剂多肽或所述载体部分融合，以上所述融合可选择地通过肽连接物而融合。
一方面，本发明提供一种前药，包括人干扰素(IFN)激动剂多肽，掩蔽部分和载体部分，其中所述掩蔽部分与人干扰素激动剂多肽结合并抑制所述人干扰素激动剂多肽的生物学活性，所述人干扰素激动剂多肽与所述载体部分融合，且所述掩蔽部分与人干扰素激动剂多肽或所述载体部分融合，以上所述融合可选择地通过肽连接物而融合。
在一些实施例中，所述IFNα为IFNα-2a，IFNα-2b，或其类似物。在一些实施例中，所述IFN为IFNα-2a，IFNα-2b，IFNγ，或其类似物。
在特定实施例中，所述IFNα-2a包括选自SEQ ID NO:65或与SEQ ID NO:65具有至少95％同源性的氨基酸序列。
在特定实施例中，所述IFNγ包括选自SEQ ID NO:5,6和7，或与SEQ ID NO:5,6或7具有至少90％同源性的氨基酸序列。在特定实施例中，所述IFNα-2b包括选自SEQ ID NO:66或与SEQ ID NO:66具有至少95％同源性的氨基酸序列。
在一些实施例中，所述IFN激动剂多肽通过不可切割肽连接物与所述载体部分融合，且所述掩蔽部分通过可切割肽连接物或不可切割肽连接物与所述载体部分融合。在其他实施例中，所述IFN激动剂多肽通过不可切割肽连接物或可切割肽连接物与所述载体融合，且所述掩蔽部分通过不可切割肽连接物与所述载体融合。
在一些实施例中，所述载体部分包括抗体Fc结构域，所述Fc结构域包括具有knob突变的第一Fc多肽链，和具有hole突变的第二Fc多肽链；其中所述IFN激动剂多肽通过可切割肽连接物与所述第一Fc多肽链融合，且所述掩蔽部分通过不可切割肽连接物与第二Fc多肽链融合。
在一些实施例中，所述载体部分为包含球孔突变(knobs-into-holes)的抗体Fc结构域或抗体，其中所述人IFN激动剂多肽和其掩蔽部分分别与抗体Fc结构域不同多肽链融合，或分别与抗体不同重链融合。
在一些实施例中，所述载体为抗体，所述前药包括两条IFN激动剂多肽和两个掩蔽部分，其中所述两条IFN激动剂多肽通过不可切割肽连接物与所述抗体两条重链的C末端融合，其中所述两个掩蔽部分通过可切割肽连接物与所述两条IFN激动剂多肽融合。
在一些实施例中，所述肽连接物为可切割肽连接物，包括以下物质的底物序列：尿激酶型纤溶酶原激活剂(uPA)、膜型基质金属蛋白酶(MT1-MMP)、基质金属蛋白酶2(MMP2)、MMP9、蛋白裂解酶、豆荚蛋白、纤溶酶、TMPRSS-3/4、组织蛋白酶,胱天蛋白酶、人嗜中性粒细胞弹性蛋白酶、β-分泌酶、或PSA，或(i)uPA和MMP2二者,(ii)uPA和MMP9二者，或(iii)蛋白裂解酶,MMP2以及MMP9。在特定实施例中，所述可切割肽连接物包括选自SEQ ID NOs:26-45的氨基酸序列。在其他特定实施例中，所述不可切割肽连接物包括选自SEQ ID NOs:122-125的氨基酸序列。在一些实施例中，所述可切割肽连接物可被位于肿瘤位点或其周围环境中的一个或多个蛋白酶切割，且切割使所述前药在肿瘤位点或其周围环境中活化。
在一些实施例中，所述掩蔽部分抑制所述IFN激动剂多肽与IFN受体的结合。在特定实施例中，所述掩蔽部分包括单链抗体(scFv)，所述scFv包括具有如SEQ ID NO:1所示的重链可变结构域，和如SEQ ID NO:2所示的轻链可变结构域；或具有如SEQ ID NO:3所示的重链可变结构域，和如SEQ ID NO:4所示的轻链可变结构域。
在一些实施例中，所述掩蔽部分选自：干扰素γ受体1胞外结构域(IFNGR1-ECD)或其功能类似物，或可与IFNγ结合的抗体或其结合片段。在特定实施例中，所述掩蔽部分包括IFNGR1-ECD或其功能类似物，并且，可选择地，所述IFNGR1-ECD包括选自SEQ ID NOs:8和9的氨基酸序列。
在一些实施例中，所述载体部分为抗体Fc结构域，抗体，或抗体的抗原结合片段。在一些实施例中，所述载体部分包括抗体或其抗原结合片段，其中所述抗体或其抗原结合片段可与肿瘤细胞、处于肿瘤微环境中的细胞、癌细胞或免疫细胞表面表达的抗原结合。在一些实施例中，所述免疫细胞选自NK细胞、T细胞、B细胞和巨噬细胞。
在一些实施例中，所述载体部分包括可与以下抗原结合的抗体或其抗原结合片段：PD-1,LAG-3,TIGIT,SIRPα,ILT2,CD206,NKD2G,CTLA-4,CD8,NKG2A,CD16a,CD38,BCMA,细胞表面糖蛋白CD2亚型1(CS1),PD-L1,CD47,CMET,EGFR,ROR1,TROP-2,HER2,CLDN18.2以及VEGFR2。
在特定实施例中，一些方面，本发明同样提供包括药物组合物和药学上可接受的赋形剂的前药；编码所述前药的核苷酸，包括所述核苷酸的表达载体，以及包括所述载体的宿主细胞。其中所述宿主细胞可以为原核细胞或真核细胞，如哺乳动物细胞。在一些实施例中，所述哺乳动物宿主细胞中编码uPA,MMP-2和/或MMP-9的基因被敲除(比如包括上述一个或多个基因的无效突变)。
在一些实施例中，本发明同样提供了制备所述前药的方法，包括在允许的条件下培养所述宿主细胞，并表达所述前药以及分离所述前药，其中，所述宿主细胞为哺乳动物细胞。
本发明同样提供了对有需要的患者治疗癌症或感染性疾病或刺激其免疫系统的方法，包括向患者施用治疗有效剂量的本公开所述的前药或药物组合物。所述患者可能患有，例如，病毒性感染或癌症，所述癌症例如可以选自乳腺癌、肺癌、胰腺癌、食管癌、甲状腺髓样癌、卵巢癌、子宫癌、前列腺癌、睾丸癌、结肠癌和胃癌。
本发明同样提供了前药或药物组合物在对有需要的患者治疗癌症、感染性疾病、或刺激其免疫系统中的应用；提供了前药在制备对有需要的患者治疗癌症、感染性疾病、或刺激其免疫系统药物中的应用；以及包括本发明所述前药的一个或多个剂量单位的制品(例如，试剂盒)。
本发明的其他特征、目的和优点在下面详细描述中是显而易见的。然而，应当理解，详细描述虽然指示了本发明的实施例和方面，但其仅以说明而非限制的方式给出。根据详细描述，本发明范围内的各种变化和修改对于本发明所述领域的技术人员而言将是显而易见的。
附图说明
图1A，1B和1C给出了干扰素前药的示意性结构。图1A为可活化的IFNα前药，其包括由抗体构成其载体部分和可切割肽连接物，其中所述前药包括两条相同的轻链，一条含有可切割连接物的重链-掩蔽部分融合多肽链，以及一条重链-细胞因子融合多肽链。图1B为IFNα前药，其包括由抗体构成其载体部分，其中所述前药包括两条相同的轻链，一条含有不可切割连接物的重链-掩蔽部分融合多肽链，以及一条重链-细胞因子融合多肽链。图1C为可活化的IFNα前药，其包括由抗体构成其载体部分和可切割连接物，其中所述前药包括两条相同的轻链和两条相同的重链多肽链，其中每条重链多肽链包括融合到重链的C末端的细胞因子，以及通过可切割肽连接物融合到细胞因子的C末端的掩蔽部分。
图2为5T4抗体JR11.60.1和前药JR11.60.2及JR11.60.3在经过蛋白A亲和柱层析纯化后的SEC-HPLC分析数据，前药JR11.60.2和JR11.60.3的结构如图1A所示。
图3A为JR11.60.1，JR11.60.2和JR11.60.3经过蛋白质A亲和柱层析纯化后的非还原性和还原性SDS-PAGE分析结果。图3B为可活化的融合分子在活化作用前后于非还原条件下的SDS-PAGE分析结果。
图4显示了不同浓度的5T4抗-IFNα前药分子JRl1.60.2和JRl1.60.3以及激活的前药分子JR11.60.2对Daudi细胞增殖的影响。其中干扰素α-2b在其中作为阳性对照。
发明详述
本文及所附权利要求书中使用的单数形式“一”个/种/项(a)、“或”(or)和“所述”/“该”(the)包括复数所指物，除非上下文另有明确规定。此处“约”一个值或参数的应用包括(并描述)该值或参数本身的变体。例如，“约X”的描述包括“X”的描述。此外，在任何一组数字前面使用“约”也包括在这一组所引用的数字中使用“约”。例如，“约X,Y或Z”的描述意在描述“约X、约Y或者约Z”。
术语“抗原结合部分”是指多肽或一组相互作用的多肽，其与抗原特异性结合，包括但不限于抗体(例如，单克隆抗体、多克隆抗体、多特异性抗体、双特异性(a dualspecific or bispecific antibody)抗体、抗独特型抗体或双功能混合抗体)，或抗原结合片段(例如Fab，Fab’，F(ab’)2，Fv，二硫键连接的Fv，scFv，单域抗体(dAb)或双抗体)，或单链抗体和含Fc的多肽，比如免疫粘附素。在一些实施方案中，抗体可以是任何重链种型(例如，IgG，IgA，IgM，IgE或IgD)或亚型(例如，IgGl，IgG2，IgG3或IgG4)。在一些实施方案中，抗体可以是任何轻链种型(例如κ或λ)。抗体可以是人的，非人的(例如，来自小鼠，大鼠，兔，山羊或另种非人的动物)，嵌合的(例如，具有非人可变区和人源恒定区)或人源化的(例如，具有非人CDR，人源构架和恒定区)。在一些实施方案中，抗体是衍生的抗体。
术语“细胞因子激动剂多肽”或“细胞因子部分”是指野生型细胞因子或其类似物。野生型细胞因子的类似物具有与野生型细胞因子相同的生物学特性(例如，与相同的受体结合并激活相同的靶细胞)，尽管该类似物的活性水平可能与野生型细胞因子有所不同。类似物可以是，例如野生型细胞因子的突变蛋白(比如，突变的多肽)，并且相对于野生型细胞因子可以包含至少一个，至少两个，至少三个，至少四个，至少五个，至少六个，至少七个，至少八个，至少九个或至少十个位点的突变。
术语“细胞因子掩蔽体”或“掩蔽部分”是指其部分(moiety)(例如多肽)与细胞因子结合，并由此抑制细胞因子与其在靶细胞表面上的受体结合，和/或在被掩蔽时抑制细胞因子发挥其生物学功能的部分。细胞因子掩蔽体的例子包括但不限于，源自于和细胞因子接触的细胞因子天然受体上胞外域的多肽。
术语“有效量”或“治疗有效量”是指化合物或组合物足以治疗特定病症、病状或疾病，例如改善、缓和、减轻和/或延迟一种或多种症状。
术语“功能类似物”是指与参考分子相比具有相同的生物特性(例如，结合至相同的配体)和/或活性(例如，激活或抑制靶细胞)的分子。
关于两个多肽序列的术语“融合(fused)”或“融合(fusion)”是指两个多肽序列通过主链肽键的链接。两个多肽可以直接融合，亦可以通过含一个或多个氨基酸的连接肽融合。融合多肽可以通过重组技术，由包含着两个融合部分的各自编码序列的一段编码序列制备，其间可具或不具连接肽的编码序列。在一些实施方案中，融合涵盖化学偶联。
术语“药学上可接受的赋形剂”当用于指组合物中的成分时，是指该赋形剂适合施用于治疗对象，包括人，而不会对该对象造成不当的毒副作用，且不会影响活性药物成分(API)的生物学活性。
术语“受试对象”是指哺乳动物，包括但不限于人，宠物(例如犬或猫)，农场动物(例如牛或马)，啮齿动物，或灵长类动物。
如本发明所述“治疗”(treatment)或“治疗”(treating)是用于获得有益的或期望的临床结果的途径。有益的或期望临床结果包括但不限于以下一种或多种：减轻由疾病引起的一种或多种症状、减轻疾病的程度、改善疾病状态、稳定疾病(例如，预防或延缓疾病的恶化或进展)、预防或延缓疾病的扩散(例如转移)、预防或延缓疾病的复发、提供疾病的部分或全部缓解、减少一种或多种其他药物治疗疾病所需的剂量、增加患者生活质量，和/或延长生存期。本发明的方法考虑了其中任何一个或多个方面的治疗。
应当理解，本发明描述的各种实施方案的一种、一些或全部性质，均可以组合以形成本发明的其他实施方案。本发明使用的章节标题仅用于组织目的，而不应将其解释为限制在此描述的主题。
I.IFN前药
本发明描述的全新细胞因子前药包括干扰素(IFN)激动剂分子(细胞因子部分)。在一些实施例中，所述前药在肿瘤位点可被活化。
所述IFN前药具有更小的副作用，更好的体内药动学(比如，更长的半衰期)以及更强的靶特异性，并且所述IFN前药相较于之前IFN疗法具有更好的疗效。本发明所述的前药包括IFN激动剂分子、掩蔽部分、载体，以及可选择地包括肽连接物。在一些实施例中，所述肽连接物为可切割的或不可切割的肽连接物。
本发明披露的干扰素激动剂分子可以选自IFNγ,IFNα-2b和IFNα-2a。在一些实施例中，IFNγ包括如SEQ ID NO:5,6或7所示的氨基酸序列。在一些实施例中，IFNγ类似物包括与SEQ ID NO:5,6或7具有至少90％同源性的氨基酸序列。在其他实施例中，IFNα-2a激动剂多肽包括SEQ ID NO:65或与SEQ ID NO:65具有至少90％同源性的氨基酸序列。在其他实施例中，IFNα-2b激动剂多肽包括SEQ ID NO:66或与SEQ ID NO:66具有至少90％同源性的氨基酸序列。
在一些实施例中，所述IFN前药包括至少一个掩蔽部分。所述掩蔽部分可以通过肽连接物连接到细胞因子部分或载体部分。在一些实施例中，所述肽连接物为不可切割肽连接物。在一些实施例中，所述肽连接物为可切割肽连接物。在一些实施例中，所述可切割肽连接物包括一个或多个可切割部分，这些可切割部分通常为在肿瘤位点的蛋白酶的底物。所述掩蔽体通过与细胞因子结合来抑制细胞因子部分的生物学功能。在特定实施例中，所述掩蔽体抑制IFNγ，IFNα-2b或IFN-2a或其类似物的生物学活性。所述前药在患者靶点(例如，在肿瘤位点或其周围环境)被活化，活化的方式通过连接物的切割，并由此释放前药的细胞因子掩蔽体，将之前被掩蔽的细胞因子部分暴露出来，并使细胞因子部分与靶细胞上的受体结合并在靶细胞上发挥其生物学功能。
在一些实施例中，前药的载体为抗原结合部分，其可在目标靶点(例如，肿瘤表面)与抗原结合。在一些实施例中，本发明所述前药在体内由载体导向的靶点处代谢为活化状态。在进一步实施例中，前药的载体为靶向到肿瘤抗原的抗体，因此所述前药能够被递送至患者的肿瘤位点实现局部代谢(例如，肿瘤微环境的内部或周围)。随后连接细胞因子掩蔽体和载体或细胞因子部分的连接物被切割，使细胞因子部分和其受体在靶细胞发生作用并在局部刺激目标免疫细胞。
在一些实施例中，所述载体选自白蛋白，Fc片段，Fc结构域，聚乙二醇(PEG)，或抗体或其抗原结合片段。
A.IFN前药的掩蔽部分
在一些实施例中，所述掩蔽部分包括IFNγ受体1胞外结构域(IFNGR1-ECD)或其片段。在一些实施例中，所述掩蔽部分包括特异性结合IFNγ，IFNα-2b和/或IFNα-2a的scFv或Fab。在一些实施例中，所述掩蔽部分抑制IFNγ，IFNα-2b或IFNα-2a或其类似物的生物学活性。在一些实施例中，所述掩蔽部分包括scFv，其中所述scFv与SEQ ID NOs:1-4具有至少99％同源性的氨基酸序列。在一些实施例中，所述掩蔽部分包括scFv，其中所述scFv与SEQID NOs:60和61具有至少99％同源性的氨基酸序列。在一些实施例中，所述scFv或Fab包括与抗体隆利珠单抗(rontalizumab)相同的轻链CDR和重链CDR。在一些实施例中，所述scFv和Fab包括氨基酸序列SEQ ID NO:62或与SEQ ID NO:62具有至少90％同源性氨基酸序列的VL结构域。在一些实施例中，所述scFv或Fab包括氨基酸序列为SEQ ID NO:63或与SEQ IDNO:63具有至少90％同源性氨基酸序列的VL结构域，和氨基酸序列为SEQ ID NO:64或与SEQID NO:64具有至少90％同源性氨基酸序列的VH结构域。在一些实施例中，所述scFv或Fab包括与专利申请WO2016/112497A1中披露的IFNα抗体相同的轻链CDR和重链CDR。在一些实施例中，所述scFv包括与西法利木单抗(sifalimumab)或隆利珠单抗(rontalizumab)相同的重链CDR1,CDR2,CDR3和轻链CDR1,CDR2,CDR3。
B.前药的载体部分
本发明前药的载体部分可以是抗原结合部分，或者不是抗原结合部分。载体部分可以改善药动学，例如细胞因子激动剂多肽的血清半衰期，还可以将细胞因子激动剂多肽靶向体内的靶位点，例如肿瘤位点。
1.非抗原结合的载体部分
非抗原结合的载体部分亦可以用于本发明的前药。例如，抗体Fc结构域(例如人IgG1,IgG2,IgG3,或IgG4 Fc)，聚合物(例如PEG)，白蛋白(例如人白蛋白)，或其片段，或纳米颗粒，均可使用。
前药的载体部分可以包括白蛋白(例如，人血清白蛋白)或其片段。在一些实施例中，所述白蛋白或白蛋白片段与人血清白蛋白或其片段具有约85％或更多，约90％或更多，约91％或更多，约92％或更多，约93％或更多，约94％或更多，约95％或更多，约96％或更多，约97％或更多，约98％或更多，约99％或更多，约99.5％或更多，或约99.8％或更多的同源性。
在一些实施例中，所述载体部分包括白蛋白片段(例如，人血清白蛋白片段)，其具有约10个或更多，20个或更多，30个或更多，40个或更多，50个或更多，60个或更多，70个或更多，80个或更多，90个或更多，100个或更多，120个或更多，140个或更多，160个或更多，180个或更多，200个或更多，250个或更多，300个或更多，350个或更多，400个或更多，450个或更多，500个或更多，或550个或更多的氨基酸长度。在一些实施例中，所述白蛋白片段的氨基酸长度在约10个氨基酸到约584个氨基酸之间(例如在约10个到约20个氨基酸之间，约20个到约40个氨基酸之间，约40个到约80个氨基酸之间，约80个到约160个氨基酸之间，约160个到约250个氨基酸之间，约250个到约350个氨基酸之间，约350个到约450个氨基酸之间，约450个到约550个氨基酸之间)。在一些实施例中，所述白蛋白片段包括Sudlow I结构域或其片段，或Sudlow II结构域或其片段。
在一些实施例中，所述载体为抗体Fc片段。Fc为含有两个N末端和两个C末端的二聚体分子。在一些实施例中，所述细胞因子部分与二聚体Fc片段中的一条Fc多肽链融合，所述掩蔽部分与另一条Fc多肽链融合。在一些实施例中，细胞因子部分和掩蔽部分分别与二聚体Fc片段中任一多肽链的C末端融合。在一些实施例中，细胞因子部分和掩蔽部分分别与二聚体Fc片段中任一多肽链的N末端融合。在一些实施例中，两个细胞因子部分分别与二聚体Fc片段中重链的C末端融合，两个掩蔽部分分别再与细胞因子部分的C末端融合。
2.抗原结合(载体)部分
所述抗原结合部分可以为抗体或其抗原结合片段，或免疫粘附素，或受体的配体。在一些实施例中，所述抗原结合部分为具有两条重链和两条轻链的完整抗体，Fab片段，Fab’片段，F(ab’)2片段，Fv片段，二硫键连接的Fv片段，单域抗体，纳米抗体或单链抗体(scFv)。在一些实施例中，所述抗原结合部分是双特异性抗原结合部分，并可以结合两个不同抗原，或同一抗原上的两个不同表位。抗原结合部分可以为细胞因子激动剂多肽提供额外的和潜在的协同治疗功效。在一些实施例中，所述抗原结合部分包括一条完整的抗体重链或一条完整抗体轻链。在一些实施例中，所述抗原结合部分包括抗体重链片段或抗体轻链片段。
在一些实施例中，细胞因子部分和抗体其中一条重链的C末端融合，细胞因子掩蔽体通过肽连接物(可选择地为可切割连接物)与抗体另一条重链的C末端融合，其中所述两条重链可选择地包括可以使两条重链特异性配对的突变。
Fc融合多肽或双特异性抗体形成异二聚体的策略是众所周知的(参见，例如Spieset al.,Mol Imm.(2015)67(2)(A):95-106)。例如，前药中的两个重链多肽可以通过“knobs-into-holes”突变形成稳定的异二聚体。进行“knobs-into-holes”突变以促进抗体重链的异二聚体的形成，并且普遍用于制造双特异性抗体(参见，例如，美国专利号8,642,745)。例如抗体的Fc结构域可在“knob链”的CH3结构域中包含T366W突变，而在“hole链”的CH3结构域中包含T366S，L368A和/或Y407V突变。还可以使用CH3域之间的另一个链间二硫桥，例如，通过将Y349C突变引入“knob链”的CH3域，并将E356C或S354C突变引入“hole链”的CH3域中(参见，例如，Merchant et al.,Nature Biotech(1998)16:677-81)。在其他实施方案中，抗体部分可在两个CH3结构域之一中包含Y349C和/或T366W突变，在另一个CH3结构域中包含E356C，T366S，L368A和/或Y407V突变。在某些特定实施方案中，抗体部分可在两个CH3结构域之一中包含Y349C和/或T366W突变，在另一个CH3结构域中包含S354C(或E356C)，T366S，L368A和/或Y407V突变；另外以一个CH3结构域上额外的Y349C突变，和另一个CH3结构域上额外的E356C或S354C突变，形成一个链间二硫键(编号始终根据Kabat的EU索引编号；Kabat et al.“Sequences of Proteins of Immunological Interest,”5th ed.,Public Health Service,National Institutes of Health,Bethesda,Md.(1991))。其他knobs-in-holes技术，比如EP1870459A1中所述的，均可以替代或附加地使用。于是，抗体部分的knobs-in-holes突变的另一个例子是在“knob链”的CH3域中带有R409D/K370E突变，在“hole链”的CH3域中带有D399K/E357K突变(EU编号)。
在一些实施例中，前药中的抗体部分在Fc结构域中包含L234A和L235A(“LALA”)突变。LALA突变消除了补体结合和固定，以及Fcγ依赖性ADCC(参见，例如，Hezareh etal.J.Virol.(2001)75(24):12161-8)。在进一步的实施例中，除了knobs-in-holes突变之外，LALA突变亦存在于抗体部分之中。
在一些实施例中，抗体部分在Fc结构域中包含M252Y/S254T/T256E(“YTE”)突变。所述YTE突变允许同步调节血清半衰期，组织分布和IgGl的活性(参见Dall’Acqua et al.,J Biol Chem.(2006)281:23514-24；和Robbie et al.Antimicrob Agents Chemother.(2013)57(12):6147-53)。在进一步的实施例中，除了knobs-in-holes突变之外，YTE突变亦存在于抗体部分中。在某特定实施例中，抗体部分具有YTE，LALA和knobs-in-holes突变或上述任何突变类型的组合。
在一些实施例中，所述抗体与PD-L1结合。在一些实施例中，所述抗体与CEA结合。在一些实施例中，所述抗体与肿瘤细胞上的抗原结合，例如，CD38,BCMA,5T4,FAP,Trop-2,PD-L1,HER-2,EGFR,Claudin 18.2,DLL-3,GCP3和CEA。所述抗体具有或不具有抗体依赖的细胞毒性(ADCC)。所述抗体进一步与细胞毒药物偶联。在一些实施例中，所述抗体与免疫细胞表面的靶标结合，激活免疫细胞并增强其抗肿瘤活性。这些抗体的实例包括下述任一：ILT-2抗体，PD-1抗体，LAG3抗体，TIGIT抗体，TGF-β抗体或CTLA4抗体。
所述抗原结合部分(载体部分)可以和细胞表面的抗原结合，如癌细胞。在一些实施例中，所述抗原结合部分为双特异性抗原结合部分，其可以与两个不同的抗原结合也可以与同一抗原的两个不同表位结合。在一些实施例中，所述抗原结合部分可结合于鸟苷酸环化酶C(GCC)，糖类抗原19-9(CA19-9)，糖蛋白A33(gpA33)，粘蛋白1(MUC1)、癌胚抗原(CEA)、胰岛素样生长因子1受体(IGF1-R),人类表皮生长因子受体2(HER2)，人类表皮生长因子受体3(HER3)，δ样蛋白3(DLL3)，δ样蛋白4(DLL4)、表皮生长因子受体(EGFR)，蛋白多糖-3(GPC3)，c-MET，血管内皮生长因子受体1(VEGFR1)，血管内皮生长因子受体2(VEGFR2)、Nectin-4、Liv-1、糖蛋白NMB(GPNMB)、前列腺特异性膜抗原(PSMA)、Trop-2、碳酸酐酶IX(CA9)，内皮素B受体(ETBR)，TF抗原(Thomsen-Friedenrech antigen，TF)、钠依赖性磷酸盐转运蛋白2b(NaPi2b)、前列腺1的6个跨膜上皮抗原(STEAP1)，叶酸受体α(FR-α)，SLIT和NTRK类蛋白6(SLITRK6)，碳酸酐酶VI(CA6)，核苷酸内焦磷酸酶/磷酸二酯酶家族成员3(ENPP3)，间皮素，滋养层糖蛋白(TPBG)，CD19,CD20,CD22,CD30,CD33,CD38,BCMA,CD40,CD56,CD66e,CD70,CD74,CD79b,CD98,CD123,CD138,CD352，程序性死亡配体1(PD-L1)，Claudin 18.2，Claudin 6，PSMA，或FAPα。在一些实施例中，所述抗原结合部分与DLL3的表皮生长因子样结构域结合。在一些实施例中，所述抗原结合部分与DLL3的Delta/Serrate/Lag2(DSL)-样结构域结合。在一些实施例中，抗原结合部分与位于GPC3的第374个氨基酸后的一个表位结合。在一些实施例中，抗原结合部分与GPC3的硫酸肝素聚糖结合。在一些实施例中，抗原结合部分与Claudin 18.2结合，但不与Claudin 18.1结合。在一些实施例中，抗原结合部分与Claudin 18.1的结合亲和力不足其与Claudin 18.2的结合亲和力的十分之一。
所述抗原结合部分可以和细胞表面的抗原结合，例如免疫细胞，例如T细胞，NK细胞，B细胞和巨噬细胞。在一些实施例中，所述抗原结合部分为双特异性抗原结合部分，其可结合两个不同的抗原或同一抗原上的两个不同的表位。在一些实施例中，所述抗原结合部分结合ILT2,PD-1,LAG-3,TIM-3,CTLA-4或TGF-β。
在一些实施例中，所述抗原结合部分包括本领域技术人员已知的抗体或其片段，所述抗体或者其片段与PD-1结合并破坏PD-1与其配体(PD-L1)之间的相互作用以刺激抗肿瘤免疫应答。在一些实施例中，抗体或其抗原结合部分与PD-1特异性结合。例如，在本发明中可以使用的靶向PD-1的抗体包含但不限于纳武利尤单抗(BMS-936558，百时美施贵宝公司)、帕博利珠单抗(MK03475或MK-3475，默克公司)、人源化抗PD-1抗体JS001(上海君实公司)、单克隆抗PD-1抗体TSR-042(Tesaro公司)、匹地利珠单抗(pidilizumab)(抗PD-1mAbCT-011，麦迪韦逊医疗公司)、抗PD-1单克隆抗体BGB-A317(百济神州公司)和/或抗PD-1抗体SHR-1210(上海恒瑞公司)、人单克隆抗体REGN2810(再生元制药公司)、人单克隆抗体MDX-1106(百时美施贵宝公司)和/或人源化抗PD-1IgG4抗体PDR001(诺华公司)。在一些实施例中，PD-1抗体来自克隆：RMP1-14(大鼠IgG)—BioXcell目录号BP0146。其它合适的抗PD-1抗体包含在美国专利第8,008,449号中公开的那些抗体。在一些实施例中，抗体或其抗原结合部分与PD-L1特异性结合并抑制其与PD-1的相互作用，从而增加免疫活性。与PD-L1结合并破坏PD-1与PD-L1之间的相互作用，并刺激抗肿瘤免疫应答的，本领域已知的任何抗体均适用于本文公开的组合治疗方法。例如，靶向PD-L1的抗体包含BMS-936559(百时美施贵宝)和MPDL3280A(基因泰克；目前正在进行人体试验)。其它合适的靶向PD-L1抗体公开于美国专利第7,943,743号中。本领域技术人员应当理解，任何与PD-1或PD-L1结合、破坏PD-1/PD-L1相互作用并刺激抗肿瘤免疫应答的抗体均适用于本文公开的组合治疗方法。
在一些实施例中，所述载体为选自ASKB1296，阿维单抗(avelumab)，阿替利珠单抗和度伐利尤单抗的抗人PD-L1抗体。
在一些实施例中，所述载体为选自达雷妥尤单抗、艾萨妥昔单抗(isatuximab)和菲泽妥单抗(felzartamab)的抗人CD38抗体。在一些实施例中，所述载体为埃罗妥珠单抗(elotuzumab)。在一些实施例中，所述载体部分包括抗体，所述抗体包括：i)具有SEQ IDNO:97或与SEQ ID NO:97具有至少95％同源性的重链可变区，和具有SEQ ID NO:98或与SEQID NO:98具有至少95％同源性的轻链可变区；或者ii)具有SEQ ID NO:99或与SEQ ID NO:99具有至少95％同源性的重链可变区，和具有SEQ ID NO:100或与SEQ ID NO:100具有至少95％同源性的轻链可变区；iii)具有SEQ ID NO:101或与SEQ ID NO:101具有至少95％同源性的重链可变区，和具有SEQ ID NO:102或与SEQ ID NO:102具有至少95％同源性的轻链可变区；或者iv)具有SEQ ID NO:103或与SEQ ID NO:103具有至少95％同源性的重链可变区，和具有SEQ ID NO:104或与SEQ ID NO:104具有至少95％同源性的轻链可变区。
示例性的抗原结合部分包括达雷妥尤单抗，艾萨妥昔单抗，和菲泽妥单抗，曲妥珠单抗，利妥昔单抗，维布妥昔单抗，西妥昔单抗，帕尼单抗(panitumumab)，GC33(或其人源化形式)，抗EGFR抗体mAb806(或其人源化形式)，抗FAP-α抗体西罗珠单抗(sibrotuzumab)(BIBH1)，和其片段。在一些实施例中，抗原结合部分与达雷妥尤单抗，艾萨妥昔单抗，和菲泽妥单抗，曲妥珠单抗，利妥昔单抗，维布妥昔单抗，西妥昔单抗，帕尼单抗，GC33(或其人源化形式)，抗EGFR抗体mAb806(或其人源化形式)，抗FAP-α抗体西罗珠单抗(BIBH1)，或其片段具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％或99％的同源性。在一些实施例中，抗原结合部分的的抗体重链与达雷妥尤单抗，艾萨妥昔单抗，和菲泽妥单抗，曲妥珠单抗，利妥昔单抗，维布妥昔单抗，西妥昔单抗，帕尼单抗，GC33(或其人源化形式)，抗EGFR抗体mAb806(或其人源化形式)，抗FAP-α抗体西罗珠单抗(BIBH1)，或其片段的重链具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％或99％的同源性。在一些实施例中，抗原结合部分的的抗体轻链与达雷妥尤单抗，艾萨妥昔单抗，和菲泽妥单抗，曲妥珠单抗，利妥昔单抗，维布妥昔单抗，西妥昔单抗，帕尼单抗，GC33(或其人源化形式)，抗EGFR抗体mAb806(或其人源化形式)，抗FAP-α抗体西罗珠单抗(BIBH1)，或其片段的轻链具有至少90％，91％，92％，93％，94％，95％，96％，97％，98％或99％的同源性。
在一些实施例中，所述抗原结合部分包括达雷妥尤单抗，艾萨妥昔单抗，和菲泽妥单抗，曲妥珠单抗，利妥昔单抗，维布妥昔单抗，西妥昔单抗，帕尼单抗，GC33(或其人源化形式)，抗EGFR抗体mAb806(或其人源化形式)，抗FAP-α抗体西罗珠单抗(BIBH1)的6个互补决定区(CDRs)。许多CDR描述是本领域已知的，并且在本文中涵盖。本领域技术人员可以基于重链或轻链可变区的序列，轻易地确定所给定描述的CDR。“Kabat”CDRs乃基于序列可变性且最为常用(Kabat et al.,Sequences of Proteins of Immunological Interest,5thEd.Public Health Service,National Institutes of Health,Bethesda,Md.(1991))。“Chothia”CDRs是指结构环的位置(Chothia&Lesk,J.Mol.Biol.(1987)196:901-917)。“AbM”CDRs代表了Kabat CDRs和Chothia结构环之间的折中，其亦被牛津分子(OxfordMolecular)的AbM抗体建模软件使用。“Contact”CDRs为基于对可用复杂晶体结构的分析。参考常见的抗体编号方案，这些CDRs的各个残基在下表1中列出。除非本文另有说明，否则抗体中的氨基酸编号是指如上文Kabat等人所述的Kabat编号方案，其包括当参照Kabat，Chothia，AbM或Contact方案进行CDR描述时。使用该编号系统，实际的线性氨基酸序列可以包含较少或额外的氨基酸，其对应于可变结构域的框架区(FR)或CDR的缩短或插入。例如，重链可变域可以包括在H2的残基52之后的单个氨基酸插入(根据Kabat的残基52a)，亦包括在重链FR残基82之后的插入的残基(例如，根据Kabat的残基82a，82b和82c等)。对于所给定的抗体，通过在抗体序列同源区域与“标准”Kabat编号序列进行比对，可以确定其抗体残基的Kabat编号。
表1：根据各种方案的CDR描述
在一些实施例中，CDRs是“扩展的CDRs”，包含根据不同方案开始或结束的区域。例如，扩展的CDR可如下所示：L24—L36,L26—L34,或L26—L36(VL-CDR1)；L46—L52,L46—L56,或L50—L55(VL-CDR2)；L91—L97(VL-CDR3)；H47—H55,H47—H65,H50—H55,H53—H58,或H53—H65(VH-CDR2)；和/或H93—H102(VH-CDR3)。
在一些实施例中，本发明提供的所述IFN前药包括载体部分，所述载体部分含有抗原结合部分，其中，所述抗原结合部分与Trop-2结合。在一些实施例中，所述IFN前药用于治疗实体瘤患者。在一些实施例中，所述前药用于治疗三阴性乳腺癌，泌尿上皮癌，小细胞肺癌，胰腺癌，肝门部胆管癌，宫颈癌和胃癌。
在一些实施例中，所述IFN前药包括载体部分，所述载体部分包括抗原结合部分，其中，所述抗原结合部分与5T4结合。在一些实施例中，所述IFN前药用于治疗实体瘤患者。在一些实施例中，所述前药用于治疗三阴性乳腺癌，小细胞肺癌，非小细胞肺癌，胰腺癌，卵巢癌和胃癌。
在一些实施例中，所述IFN前药包括载体部分，所述载体部分含有抗原结合部分，其中所述抗原结合部分与Claudin18.2结合。在一些实施例中，所述IFN前药用于对患有胰腺癌或胃癌的患者进行治疗。
在一些实施例中，所述IFN前药包括载体，所述载体包括抗原结合部分，其中，所述抗原结合部分与EGFR III结合，在一些实施例中，所述IFN用于对患有肺癌、恶性胶质瘤和结肠癌患者进行治疗。
在一些实施例中，所述IFN前药包括载体，所述载体包括抗原结合部分，其中，所述抗原结合部分与CD38或BCMA结合，在一些实施例中，所述IFN用于对患有多发性骨髓瘤的患者进行治疗。
在一些实施例中，所述IFN前药与免疫检查点阻滞剂联合使用，所述免疫检查点阻滞剂如PD-1抗体或其PD-1抗体片段。
C.前药的连接部分
所述IFN激动剂多肽(细胞因子部分)可通过或不通过肽连接物与所述载体部分融合。所述肽连接物可以为不可切割的并可选自以下序列：GGGGS(SEQ ID NO:122),GGGGSGGGGS(SEQ ID NO:123),GGGGSGGGGSGGGGS(SEQ ID NO:124),或GGGGSGGGGSAAGGGGSGGGGS(SEQ ID NO:125)。
所述掩蔽部分可通过不可切割连接物或可切割连接物与所述细胞因子部分、载体或另一掩蔽体融合。所述可切割连接物包括一个或多个(例如，两个或三个)可切割部分(CM)。每个CM可以是选自豆蔻蛋白酶、纤溶酶、TMPRSS-3/4、MMP-2、MMP-9、MT1-MMP、组织蛋白酶、胱天蛋白酶、人嗜中性粒细胞弹性蛋白酶、β-分泌酶、uPA和PSA的酶或蛋白酶的底物。可切割连接物的实施例包括，但不限于，那些选自SEQ ID NOs:26-45的氨基酸序列。
II.IFN前药实施方式
在一些实施例中，所述IFN前药包括抗体或Fc结构域以及IFN激动剂多肽，其中，所述IFN激动剂多肽可选择地通过肽连接物与抗体其中一条重链或Fc结构域中的其中一条Fc多肽链的C末端融合，其中所述掩蔽部分通过可切割肽连接物与另一条重链或另一条Fc多肽链的C末端融合。在一些实施例中，细胞因子部分和掩蔽部分位于Fc结构域的N末端。
例如，IFNα前药包括如图1A，1B或1C所示的结构。图1A为可活化的IFNα前药，所述IFNα前药以抗体作为其载体并包含可切割连接物，其中，所述前药包含两条相同的轻链，一条含有可切割连接物的重链-掩蔽体融合多肽链，以及一条重链-细胞因子融合多肽链。图1B为以抗体作为其载体的IFNα前药，其中，所述前药包含两条相同的轻链，一条含有不可切割连接物的重链-掩蔽体融合多肽链，以及一条重链-细胞因子融合多肽链。图1C为可活化的IFNα前药，所述IFNα前药以抗体作为其载体并包含可切割连接物，其中，所述前药包含两条相同的轻链和两条相同的重链多肽链，其中，每条重链多肽链包含一个与所述重链C末端融合的细胞因子和一个通过可切割连接物与任一细胞因子C末端融合的掩蔽体。
例如，所述IFNγ前药包含第一多肽链和第二多肽链，其中，所述第一多肽链包括选自SEQ ID NOs:14,15,16和17,或与SEQ ID NO:14,15,16或17具有至少90％、至少95％、或至少99％同源性的氨基酸序列，且所述第二多肽链包括选自SEQ ID NOs:18和19，或与SEQID NO:18或19具有至少90，至少95％，或至少99％同源性的氨基酸序列。
例如，所述IFNγ前药包含第一多肽链和第二多肽链，其中，所述第一多肽链包括选自SEQ ID NOs:20,21,22,和23，或与SEQ ID NO:20,21,22或23具有至少90％，至少95％，或至少99％同源性的氨基酸序列，且所述第二多肽链包括选自SEQ ID NOs:24和25，或与SEQID NO:24或25具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNγ前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括SEQ ID NO:46或与SEQ ID NO:46具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:47,48,49和50，或与SEQ ID NOs:47,48,49或50具有至少90％，至少95％，或至少99％同源性的氨基酸序列，以及所述第二重链多肽链包括选自SEQ ID NOs:51和52，或与SEQ ID NO:51或52具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNγ前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括SEQ ID NO:53或与SEQ ID NO:53具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:54,55,56和57，或与SEQ ID NO:54,55,56或57具有至少90％，至少95％，或至少99％同源性的氨基酸序列，以及所述第二重链多肽链包括选自SEQ ID NOs:58和59，或与SEQ ID NO:58或59具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNα前药包括第一多肽链和第二多肽链，其中，所述第一多肽链包括选自SEQ ID NOs:67,68,69和70，或与SEQ ID NO:67,68,69或70具有至少90％，至少95％或至少99％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NOs:71和72，或与SEQID NO:71或72具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNα前药包括第一多肽链和第二多肽链，其中，所述第一多肽链包括选自SEQ ID NOs:73,74,75和76，或与SEQ ID NO:73,74,75或76具有至少90％，至少95％或至少99％同源性的氨基酸序列；以及所述第二多肽链包括选自SEQ ID NO:77和78，或与SEQID NO:77或78具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNα前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括SEQ ID NO:46或与SEQ ID NO:46具有至少90％，至少95％或至少99％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:79,80,81和82，或与SEQ IDNO:79,80,81或82具有至少90％，至少95％或至少99％同源性的氨基酸序列，以及所述第二重链多肽链包括选自SEQ ID NOs:83和84，或与SEQ ID NO:83或84具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNα前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括SEQ ID NO:53或与SEQ ID NO:53具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:85,86,87和88，或与SEQ ID NO:85,86,87或88具有至少90％，至少95％或至少99％同源性的氨基酸序列，以及所述第二重链多肽链包括SEQID NOs:89和90，或与SEQ ID NO:89或90具有至少90％，至少95％或至少99％同源性的氨基酸序列。
例如，所述IFNα前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括SEQ ID NO:120或与SEQ ID NO:120具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:113和114，或与SEQ ID NO:113或114具有至少98％同源性的氨基酸序列，以及所述第二重链多肽链包括选自SEQ ID NOs:115,116,117,118和119，或与SEQ ID NO:115,116,117,118或119具有至少98％同源性的氨基酸序列。
例如，所述IFNα前药包括两条相同的轻链和两条相同的重链多肽链，其中，所述轻链包括SEQ ID NO:94，或与SEQ ID NO:94具有至少95％同源性的氨基酸序列，以及所述重链多肽链包括氨基酸序列SEQ ID NO:126。例如，所述IFNα前药包括两条相同的轻链和两条相同的重链多肽链，其中，所述轻链包括SEQ ID NO:96或与SEQ ID NO:96具有至少95％同源性的氨基酸序列，所述重链多肽链包括SEQ ID NO:127或与SEQ ID NO:127具有至少98％同源性的氨基酸序列。
III.药物组合物
所述前药的药物组合物可通过，将所需纯度的本发明所述前药、或抗体融合分子或抗体融合分子药物偶联物，与一个或多个可选的药学上可接受的载体进行混合以制备(参见，Osol,A.Ed.Remington's Pharmaceutical Sciences 16th edition(1980))，其形式为冻干制剂或水溶液。药学上可接受的载体通常在使用的剂量和浓度下对给予者无毒，包括但不限于：缓冲剂例如，磷酸盐，柠檬酸盐，与其他有机酸；抗氧化剂，包括抗坏血酸和蛋氨酸；防腐剂(例如十八烷基二甲基苄基氯化铵；六甲基氯化铵；苯扎氯铵；苄索氯铵；苯酚，丁醇或苄醇；对羟基苯甲酸烷基酯如对羟基苯甲酸甲酯或对羟基苯甲酸丙酯；邻苯二酚；间苯二酚；环己醇；3-戊醇和间甲酚)；低分子量(少于约10个残基)多肽；蛋白质，例如血清白蛋白，明胶或免疫球蛋白；亲水性聚合物，例如聚乙烯吡咯烷酮；氨基酸，例如甘氨酸，谷氨酰胺，天冬酰胺，组氨酸，精氨酸或赖氨酸；单糖，二糖和其他碳水化合物，包括葡萄糖，甘露糖或糊精；螯合剂，如EDTA；糖，例如蔗糖，甘露醇，海藻糖或山梨糖醇；成盐的抗衡离子，例如钠；金属配合物(例如锌-蛋白配合物)；和/或非离子表面活性剂，例如聚乙二醇(PEG)。
缓冲液用于将pH控制在最佳的治疗效果范围内，特别是当稳定性依赖于pH时。缓冲液浓度最好在50mM到250mM之间。适用于与本发明一起使用的缓冲剂包括有机和无机酸及其盐类，如柠檬酸盐、磷酸盐、琥珀酸盐、酒石酸盐、富马酸盐、葡萄糖酸盐、草酸盐、乳酸盐和醋酸盐。此外，缓冲液可包括组氨酸和三甲胺盐，如三羟甲基氨基甲烷。
添加防腐剂以减缓微生物的生长，通常在0.2％-1.0％(w/v)范围内使用。本发明使用的适用防腐剂包括十八烷基二甲基苄基氯化铵；六甲铵氯化物；苯扎卤铵(如氯、溴、碘)、苯扎氯铵；硫柳汞、苯酚、丁基或苄醇；羟苯甲酸酯类，例如羟苯甲酸甲酯或羟苯甲酸丙酯；邻苯二酚；间苯二酚；环己醇，3-戊醇和间甲酚。
张度剂，有时称为“稳定剂”，是用以调节或维持成分中液体的张力。当其与带电荷的大型生物分子(如蛋白质和抗体)一起使用时，它们通常被称为“稳定剂”，因其可与氨基酸侧链的带电基团相互作用，从而降低了分子间和分子内相互作用的可能性。当考虑其他成分的相对量时，张度剂可在0.1％至25％重量比之间的任何量使用，或更优选于1％至5％重量比之间。优选的张度剂包括多元糖醇，更优选地为三元或更高级的糖醇，例如甘油，赤藓糖醇，阿拉伯糖醇，木糖醇，山梨糖醇和甘露糖醇。
非离子表面活性剂或去污剂(也称为“湿润剂”)，被用以帮助溶解治疗剂，并保护治疗蛋白避免因搅动所导致的聚集，其亦允许了该制剂配方可暴露于剪切表面应力而不引起活性治疗性蛋白或抗体的变性。非离子表面活性剂的使用范围为约0.05mg/ml至约1.0mg/ml，优选为约0.07mg/ml至约0.2mg/ml。
合适的非离子表面活性剂包括聚山梨酯(20、40、60、65、80等)，泊咯沙姆(184、188等)，普朗尼克多元醇，曲拉通，聚氧乙烯山梨糖醇单醚(吐温-20，吐温-80等)，聚桂醇400，聚氧化烯硬脂酸酯40，聚氧乙烯氢化蓖麻油10、50和60，单硬脂酸甘油酯，蔗糖脂肪酸酯，甲基纤维素和羧甲基纤维素。可使用的阴离子去污剂包括月桂基硫酸钠，磺基琥珀酸二辛酯钠和磺酸二辛基钠。阳离子去污剂包括苯扎氯铵或苄索氯铵。
药物载体、赋形剂或稀释剂的选择可以根据预期施用途径和标准药物实践进行选择。除载体、赋形剂或稀释剂之外，药物组合物还包含任何合适的粘合剂，润滑剂，助悬剂，包衣剂或增溶剂。
取决于不同的给药途径，可能存在不同的组成/配方要求。举例来说，本发明有效的药物组合物可配制成使用微型泵或通过粘膜途径给药的形式，例如作为用于吸入或可吸收溶液的鼻喷雾剂或气雾剂，或其中组合物可配制成注射液形式，给药途径通过例如静脉，肌肉或皮下注射。或者，可以将制剂设计成通过多种途径给药。在一些实施方案中，所述制剂直接在一个或多个肿瘤中施用。
在一些实施例中，抗体或蛋白制剂为冻干制剂，在另一些实施例中，抗体或蛋白制剂为液体制剂
在一些实施例中，所述药物组合物为药物组合物的结合，其包括本发明所述的IFN前药，药学上可接受的赋形剂，和第二活性成分，所述第二活性成分选自除了IFN，或其前药或融合分子的细胞因子，抗PD-1抗体，抗PD-L1抗体，抗CTLA-4抗体，抗CD47抗体，PD-1抗体-IL-15融合分子，PD-1-IL-2融合分子，以及PD-1-IL-21融合分子。
IV.治疗方法
本发明披露的前药可以根据抗原和抗原结合部分的结合用于治疗疾病。在一些实施例中，本发明披露的前药用于治疗癌症。在一些实施例中，例如，当药物分子为抗菌药或抗病毒药时，所述前药可用于治疗感染性疾病。
在一些实施例中，治疗受试者疾病(例如癌症，病毒感染或细菌感染)的方法包含向受试对象施用有效剂量的本发明披露的前药。
在一些实施例中，所述癌症为实体瘤。在一些实施例中，所述癌症为血液肿瘤。可治疗的示例性癌症包括，但不限于，白血病，淋巴瘤，肾癌，膀胱癌，泌尿道癌，宫颈癌，脑癌，头颈癌，皮肤癌，子宫癌，睾丸癌，食道癌，肝癌，结肠癌，胃癌，鳞状细胞癌，前列腺癌，胰腺癌，肺癌，胆管癌，乳腺癌和卵巢癌。
在一些实施例中，本发明披露的前药用于治疗细菌感染，如败血症。在一些实施例中，引起细菌感染的细菌为耐药细菌。在一些实施例中，所述抗原结合部分与细菌抗原结合。
在一些实施例中，本发明披露的前药用于治疗病毒感染。在一些实施例中，引起病毒感染的病毒是丙型肝炎病毒(HCV)、乙型肝炎病毒(HBV)、人体免疫缺陷病毒(HIV)或人乳头瘤病毒(HPV)。在一些实施例中，所述抗原结合部分与病毒抗原结合。
一般来讲，现有药物的给药剂量和给药途径是根据受试者的情况和条件，按照标准的药学实践来确定。在一些实施例中，药物组合物的给予是通过任一给药途径，包括口服，皮下，吸入，静脉注射，动脉内的，肌肉，直接应用于伤口，应用手术部位，腹腔内，栓剂，皮下，皮内注射，经皮，雾化，胸膜腔内，脑室，关节内的，眼内，颅内或脊柱内。在一些实施例中，药物通过静脉注射的方式施用于患者。
在一些实施例中，所述前药以单剂量或重复剂量的形式施用给受试者。在一些实施例中，剂量为每天一次，每天两次，每天三次，或每天四次或每天更多次给予受试者。在一些实施例中，一周内给予约1次或更多(例如约2,3,4,5,6或7或更多次)剂量。在一些实施例中，与药物偶联的抗体融合分子以每周一次，每两周一次，每三周一次，每四周一次，每三周中的两周进行按周给药，或每四周中的三周进行按周给药。在一些实施例中，多剂量于几天，几周，几个月或几年的疗程中给予。在一些实施例中，疗程为约1或更多剂量(例如约2,3,4,5,7,10,15或20或更多剂量)。
在一些实施例中，所述IFN前药与第二药物组合物联合施用于受试者，其中，所述第二药物组合物包括活性成分，所述活性成分选自除了IFN或其前药或融合分子的细胞因子，抗PD-1抗体，抗PD-L1抗体，抗CTLA-4抗体，抗CD47抗体，PD-1抗体-IL-2融合分子，PD-1-IL-7融合分子，PD-1抗体-IL-15融合分子，和PD-1-IL-21融合分子。
V.前药制备方法
本发明披露的前药可通过重组DNA方法制备。将编码所述前药多肽或融合多肽的核酸分离出来，并将其插入到一个或多个载体中以使其在宿主细胞中进一步克隆和/或表达。所述核酸分子可很容易的通过传统方法被分离和测序。适合克隆或表达融合多肽载体的宿主细胞包括原核细胞和真核细胞。示例性的宿主细胞包括中国仓鼠卵巢细胞(CHO)或人胚肾细胞(例如，HEK293)。
用于表达的宿主细胞表达所述抗体融合分子，宿主细胞完成表达后，将所述宿主细胞裂解，并纯化前药或抗体融合分子。示例性的纯化方法包括液相色谱，例如离子交换色谱，亲和色谱(例如，蛋白A亲和色谱)，或尺寸排阻色谱法。
VI.示例性的实施例
本发明的其他特定实施例描述如下。这些实施方案旨在说明本发明中描述的成分和方法，而并非旨在限制本发明的范围。
1、干扰素γ(IFNγ)前药，其包括IFNγ激动剂多肽和掩蔽部分，其中所述掩蔽部分与IFNγ结合并抑制IFNγ的生物学活性；并且所述IFNγ包括选自SEQ ID NO:5,6,和7或与SEQID NO:5,6或7具有至少90％同源性的氨基酸序列。
2、实施例1所述的前药，其中所述掩蔽部分选自干扰素γ受体1胞外结构域(IFGR1-ECD)或其功能类似物，或与IFNγ结合的抗体或其结合片段。
3、实施例1,2或3所述的前药，其中所述掩蔽部分包括IFGR1-ECD或其功能类似物；并且所述IFGR1-ECD包括选自SEQ ID NOs:8和9的氨基酸序列。
4、实施例1,2或3所述的前药，其中所述掩蔽部分包括scFv，所述scFv包括选自SEQID NOs:1-4，或与SEQ ID NOs:1,2,3或4具有至少90％同源性的氨基酸序列。
5、实施例1,2,3，或4所述的前药，其进一步包括载体部分，所述载体部分选自Fc结构域，抗原结合部分，或白蛋白或其片段。
6、实施例1,2,3,或4所述的前药，其进一步包括载体部分，其中所述载体部分包括抗体的Fc结构域。
7、实施例1,2,3，或4所述的前药，其进一步包括载体部分，其中所述载体部分包括与肿瘤细胞、癌细胞或免疫细胞表面表达抗原结合的抗体。
8、实施例7所述的前药，其中所述免疫细胞选自NK细胞，T细胞，B细胞及巨噬细胞。
9、实施例1,2,3或4所述的前药，其进一步包括载体部分，其中所述载体部分包括与选自PD-1,LAG-3,SIRPα,ILT2,CD206,NKD2G,CTLA-4,CD8,以及CD16a的抗原结合的抗体。
10、实施例1,2,3，或4所述的前药，其进一步包括载体部分，其中所述载体部分包括与选自PD-L1,CD47,CMET,EGFR,ROR1,TROP-2,HER2,CLDN18.2,以及VEGFR2的抗原结合的抗体。
11、实施例1,2,3或4所述的前药，其进一步包括载体部分，其中所述载体部分包括与PD-1结合的抗体，并且其中所述抗体包括具有氨基酸序列SEQ ID NO:10的轻链可变区结构域以及具有氨基酸序列SEQ ID NO:11的重链可变区结构域，或具有氨基酸序列SEQ IDNO:12的轻链可变区结构域和具有氨基酸序列SEQ ID NO:13的重链可变区结构域。
12、实施例1-11任一项所述的前药，其进一步包括可切割肽连接物，所述可切割肽连接物可被肿瘤细胞表达或肿瘤细胞附近表达的酶所切割。
13、实施例6所述的前药，其中所述可切割肽连接物包括选自SEQ ID NOs:26-45所述的氨基酸序列。
14、IFNγ前药，其包括第一多肽链和第二多肽链，其中所述第一多肽链包括选自SEQ ID NOs:14,15,16和17或与SEQ ID NO:14,15,16或17具有至少95％同源性的氨基酸序列，且所述第二多肽链包括选自SEQ ID NOs:18和19或与SEQ ID NO:18或19具有至少95％同源性的氨基酸序列。
15、IFNγ前药，其包括第一多肽链和第二多肽链，其中所述第一多肽链包括选自SEQ ID NOs:20,21,22和23或与SEQ ID NO:20,21,22或23具有至少95％同源性的氨基酸序列，所述第二多肽链包括选自SEQ ID NOs:24和25或与SEQ ID NO:24或25具有至少95％同源性的氨基酸序列。
16、IFNγ前药，其包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中所述轻链包括SEQ ID NO:46或与SEQ ID NO:46具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:47,48,49和50或与SEQ ID NOs:47,48,49或50具有至少98％同源性的氨基酸序列，且所述第二重链多肽链包括选自SEQ ID NOs:51和52或与SEQID NO:51或52具有至少98％同源性的氨基酸序列。
17、IFNγ前药，其包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中所述轻链包括SEQ ID NO:53或与SEQ ID NO:53具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:54,55,56和57或与SEQ ID NO:54,55,56或57具有至少98％同源性的氨基酸序列，且所述第二重链多肽链包括选自SEQ ID NOs:58和59或与SEQID NO:58或59具有至少98％同源性的氨基酸序列。
18、干扰素α(IFNα)前药，其包括IFNα激动剂多肽，掩蔽部分和载体部分，其中所述掩蔽部分包括与所述IFNα激动剂结合的Fab，纳米抗体或单域抗体(scFv)。
19、实施例18所述的前药，其中所述IFNα包括选自SEQ ID NOs:65和66或与SEQ IDNO:65或66具有至少95％同源性的氨基酸序列。
20、实施例18或19所述的前药，其中所述掩蔽部分包括scFv，所述scFv包括包括与衍生自西法利木单抗和隆利珠单抗相同的重链CDR1,CDR2,CDR3和轻链CDR1,CDR2,CDR3。
21、实施例18或19所述的前药，其中所述掩蔽部分包括scFv，其包括SEQ ID NO:63或与SEQ ID NO:63具有至少95％同源性氨基酸序列的VL结构域，和SEQ ID NO:64或与SEQID NO:64具有至少95％同源性氨基酸序列的VH结构域。
22、实施例18或19所述的前药，其中所述掩蔽部分包括scFv，所述scFv包括SEQ IDNO:60或61或与SEQ ID NO:60或61具有至少95％同源性的氨基酸序列。
23、实施例18-22所述的前药，其中所述载体部分选自Fc结构域，抗原结合部分，或白蛋白或其片段。
24、实施例18-22所述的前药，其中所述载体部分包括与肿瘤细胞、癌细胞或免疫细胞表面表达抗原结合的抗体。
25、实施例24所述的前药，其中所述免疫细胞选自NK细胞、T细胞、B细胞和巨噬细胞。
26、实施例18-22所述的前药，其中所述载体部分包括与选自PD-1、LAG-3、SIRPα、ILT2、CD206、NKD2G、CTLA-4、CD8以及CD16a的抗原结合的抗体。
27、实施例18-22所述的前药，其中所述载体部分包括与选自PD-L1、CD47、CMET、EGFR、ROR1、TROP-2、HER2、CLDN18.2以及VEGFR2的抗原结合的抗体。
28、实施例18-22所述的前药，其中所述载体部分包括与PD-1结合的抗体，且其中所述抗体包括具有SEQ ID NO:10氨基酸序列的轻链可变区结构域和具有SEQ IDNO:11氨基酸序列的重链可变区结构域，或具有SEQ ID NO:12氨基酸序列的轻链可变区结构域和具有SEQ ID NO:13氨基酸序列的重链可变区结构域。
29、实施例18-28所述的前药，其进一步包括可切割肽连接物，所述可切割肽连接物可被肿瘤细胞表达或肿瘤细胞附近表达的酶所切割。
30、实施例29所述的前药，其中所述可切割肽连接物包括选自SEQ ID NOs:26-45的氨基酸序列。
31、INFα前药，其包括第一多肽链和第二多肽链，所述第一多肽链包括选自SEQ IDNOs:67,68,69和70或与SEQ ID NO:67,68,69或70具有至少95％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NOs:71和72或与SEQ ID NO:71或72具有至少95％同源性的氨基酸序列。
32、IFNα前药，其包括第一多肽链和第二多肽链，其中所述第一多肽链包括选自SEQ ID NOs:73,74,75和76或与SEQ ID NO:73,74,75或76具有至少95％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NO:77,78或与SEQ ID NO:77或78具有至少95％同源性的氨基酸序列。
33、IFNα前药，其包括两条相同的轻链，第一重链多肽链和第二重链多肽连，其中所述轻链包括SEQ ID NO:46或与SEQ ID NO:46具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:79,80,81和82或与SEQ ID NO:79,80,81或82具有至少98％同源性的氨基酸序列，以及所述第二重链多肽链包括选自SEQ ID NOs:83和84或与SEQID NO:83或84具有至少98％同源性的氨基酸序列。
34、IFNα前药，其包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中所述轻链包括SEQ ID NO:53或与SEQ ID NO:53具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:85,86,87和88或与SEQ ID NO:85,86,87或88具有至少98％同源性的氨基酸序列，以及第二重链多肽链包括选自SEQ ID NOs:89和90或与SEQ IDNO:89或90具有至少98％同源性的氨基酸序列。
35、一种药物组合物，其包括实施例1-34任一项所述的前药作为其活性成分，及药学上可接受的赋形剂。
36、实施例35所述的药物组合物，其进一步包括CD47拮抗剂，SIRPα拮抗剂，或CTLA4拮抗剂。
37、编码实施例1-34任一项所述嵌合分子的多核苷酸。
38、包括实施例37所述多核苷酸的表达载体。
39、包括实施例38所述表达载体的宿主细胞。
40、实施例39所述的宿主细胞，其中所述宿主细胞中编码uPA,MMP-2,MMP-9和/或蛋白裂解酶的基因被敲除
41、制备实施例1-34任一项所述嵌合分子的方法，包括：
在允许所述嵌合分子表达的条件下培养实施例39或40所述的宿主细胞，
分离所述嵌合分子。
42、对有需要的患者治疗癌症或感染性疾病或刺激其免疫系统的方法，包括施用根据实施例1-34任一项所述的前药或根据实施例35或36所述的药物组合物。
43、对有需要的患者治疗癌症的方法，包括施用根据实施例1-34任一项所述的前药或根据实施例35所述的药物组合物，其中所述患者同时被施用包括CD47拮抗剂、IL T2拮抗剂、SIRPα拮抗剂、抗PD-1抗体、抗CTLA-4抗体或抗PD-1抗体的药物组合物。
44、癌症患者的治疗方法，包括将根据实施例1-34任一项所述的前药或根据实施例35或36所述的药物组合物直接用于肿瘤或肿瘤组织。
45、根据实施例42.43或44所述的方法，其中所述癌症选自乳腺癌，肺癌、胰腺癌、食管癌、甲状腺髓样癌、卵巢癌、子宫癌、前列腺癌、睾丸癌、结肠癌和胃癌。
应当理解，尽管通过参考具体实施例突出了本说明书的各方面，但是本领域技术人员容易理解这些公开的实施例仅说明本发明公开主题的原理。因此应当理解的是，除非明确说明，否则所公开的主题不限于本文所述的特定化合物，组合物，制品，或方法。另外，本领域普通技术人员将认识到，可以根据本文的教导进行某些改变，修改，置换，变更，增加，减少和进一步组合，而不背离本说明书的主题。
除非本文另有定义，否则结合本公开使用的科学和技术术语应具有本领域的普通技术人员通常理解的含义。下文描述的示例性方法和材料，但是与本文所述的那些方法和材料类似的或等同的方法和材料也可以用于本公开的实践或测试。在发生冲突的情况下，应以本说明书(包含定义)为准。通常，本文所述的与细胞和组织培养、分子生物学、免疫学、微生物学、遗传学、分析化学、合成有机化学、药用和药物化学以及蛋白质和核酸化学和杂交结合使用的术语表达和技术是本领域众所周知的和常用的表达。如本领域通常实现的或如本文所描述的来根据制造商的说明执行酶促反应和纯化技术。此外，除非上下文另有要求，否则单数术语应包含复数含义并且复数术语应包含单数含义。贯穿本说明书和实施例，词语“具有(have)”“包括(comprise)”或如“具有(has)”，“具有(having)”，“包括(comprises)”或“包括(comprising)”等变体应当被理解为暗示包含所陈述整数或整数组，但不排除任何其他整数或整数组。应当理解，本文所述的本发明的方面和变体包含”由方面和变体组成”和/或“基本上由方面和变体组成”。本文提及的所有出版物和其他参考文献以全文引用的方式并入，尽管本文引用了许多文件，但此引用并不构成承认这些文件中的任何文件形成本领域公知常识的一部分。
为了更好地理解本发明，阐述以下实例。这些实例仅出于说明目的并且不应该被解释为以任何方式限制本发明的范围。
实施例
实施例1：Expi CHO细胞的瞬时转染
利用ExpiFectaminTMCHO转染试剂盒(Giboco)将表达质粒以1μg/ml的浓度与细胞密度为6*106个细胞/ml的Freestyle ExpiCHO细胞共转染。对于抗体，其中，HC和LC的比例为1:2。对于抗体-融合IFNα前药，其中，HC-IFNα融合多肽，HC-掩蔽部分融合多肽和LC的比例为1:1.5:4。表2给出了5T4抗体JR11.60.1和表达的5T4抗体-IFNα前药分子JR11.60.2和JR11.60.3的序列编号。转染7天后，收集细胞培养液，并于9000rpm的转速离心45分钟，然后进行0.22μM过滤。
表2：在瞬时转染中表达IFNα前药的序列编号
实施例2：IFNα前药的纯化
利用蛋白A亲和柱层析对IFNα前药进行纯化，利用其它层析或过滤步骤对其进行进一步纯化，例如可采用树脂层析步骤，例如可采用CaptoTM MMC ImpRes，CaptoTM Adhere，CaptoTM SP，和/或Q Sepharose FF对所述前药进行进一步纯化。
实施例3：SEC-HPLC分析
SEC-HPLC的分析是在Agilent 1100系列HPLC系统上进行并以从TosohBioscience订购的TSKgel G3000SWXL为层析柱(7.8mmID*30cm，粒径5μm)。样品装载量不超过100μl，色谱柱的流动相为200mM K3PO4、250mM KCl，pH6.5的缓冲液。流速设定为0.5ml/min。柱温为室温。蛋白质洗脱的检测UV波长为220nm和280nm。图2展示了5T4抗体JR11.60.1和前药JR11.60.2和JR11.60.3经蛋白A亲和柱层析纯化后的SEC-HPLC数据。
实施例4：SDS-PAGE分析
将10μl培养物上清液或4μg纯化后的蛋白样品与具有或不具有还原剂的BoltTMLDS样品缓冲液(Novex)混合。样品于70℃加热3分钟，然后加载到NuPAGETM 4-12％BisTris凝胶(InvitrogenTM)上。该凝胶在NuPAGETM MOPS SDS运行缓冲液(InvitrogenTM)中以200伏特运行35分钟，然后使用考马斯染色。图3展示了JR11.60.1，JR11.60.2和JR11.60.3经蛋白A亲和柱层析纯化后的非还原和还原SDS-PAGE分析结果。在还原SDS-PAGE分析中，轻链和重链多肽链显示为具有预期的分子量。
实施例5：蛋白水解处理
将1μg的蛋白酶，人MMP-2(R&D systems)，人MMP-9(R&D systems)，小鼠MMP-2(R&Dsystems)，或小鼠MMP-9(R&D systems)加入到50μg的前体蛋白中，于37℃条件下孵育过夜。图3B展示了可活化的融合分子在活化前后的SDS-PAGE(非还原的)分析结果，可以看出，酶解作用降低了融合分子的分子量。
实施例6：抗增殖分析
I型干扰素抑制某些肿瘤细胞系的活性早已为人所知。多种可能的作用机制使其具有该活性，包括下调转录因子c-myc和抑制肿瘤抑制蛋白pRb的磷酸化作用，以上两个作用均可导致细胞周期停滞。IFNα的治疗也可上调促凋亡蛋白，例如Fas，FasL和TRAIL。为了检测其抗增殖效应，将连续稀释的测试样品接种至含有100mL/孔分析培养基(RPMI 1640，10％FBS，NEAA，Pyruvate，NEAA，β-巯基乙醇))的96孔板中。待测细胞系以5000或10000细胞/孔的密度加入100mL培养基中。将培养物在37℃条件下孵育3天后，去除100mL的培养上清液，并替换为100mL的CellTiter(Promega,Catalog#G9241)。利用光度计测试其发光强度(luminescence)。CellTiter />通过测定ATP活性来检测活细胞数量。通过四参数(4PL)逻辑回归模型的拟合得到所述样品的EC50值。
图4展示了Daudi细胞分别在不同浓度的5T4抗体-IFNα前药分子JR11.60.2和JR11.60.3以及活化后的JR11.60.2中的增殖情况，其中IFNα-2b作为阳性对照。结果显示，前药分子JR11.60.2在蛋白酶MMP-2的活化作用下，其生物学活性增加约50倍。另外，研究人员意外地发现，JR11.60.2及活化的JR11.60.2二者相较于对照IFNα-2b均明显地具有更低的效价强度，意味着所述前药比野生型干扰素更加安全。
上述非限制性示例仅出于说明性目的而提供，以便于更全面地理解所公开的主题。这些示例不应被解释为限制本说明书中描述的任何实施方案，包括那些涉及抗体，药物成分，或用于治疗癌症，神经变性或感染性疾病的方法或用途的实施方案。
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序列表
<110> 奥美药业有限公司
<120> 干扰素前药、制备方法及应用
<130> 025471.WO014
<140>
<141>
<150> 63/137,370
<151> 2021-01-14
<160> 127
<170> PatentIn version 3.5
<210> 1
<211> 240
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 1
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asn Val Asp Thr Tyr
20 25 30
Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr Asn Tyr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ser Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Ser Trp Ile Asn Trp Val
145 150 155 160
Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro
165 170 175
Ser Asp Gly Glu Val His Tyr Asn Gln Asp Phe Lys Asp Lys Ala Thr
180 185 190
Leu Thr Val Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser
195 200 205
Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Phe Leu
210 215 220
Pro Trp Phe Ala Asp Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235 240
<210> 2
<211> 240
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 2
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Ser
20 25 30
Trp Ile Asn Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Ser Asp Gly Glu Val His Tyr Asn Gln Asp Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Phe Leu Pro Trp Phe Ala Asp Trp Gly Arg Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser
130 135 140
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asn
145 150 155 160
Val Asp Thr Tyr Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro
165 170 175
Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser
180 185 190
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
195 200 205
Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr
210 215 220
Asn Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg
225 230 235 240
<210> 3
<211> 240
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 3
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg Ser Gly Gly Ser Ser
85 90 95
Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser
130 135 140
Cys Lys Gly Ser Gly Tyr Asn Phe Thr Ser Tyr Trp Ile Gly Trp Val
145 150 155 160
Arg Gln Met Pro Gly Lys Gly Leu Glu Leu Met Gly Ile Ile Tyr Pro
165 170 175
Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr
180 185 190
Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr Leu Gln Trp Ser Ser
195 200 205
Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Gly Ser Gly Ser Tyr
210 215 220
Phe Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
225 230 235 240
<210> 4
<211> 240
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 4
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Asn Phe Thr Ser Tyr
20 25 30
Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Leu Met
35 40 45
Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Gly Ser Gly Ser Tyr Phe Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
130 135 140
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
145 150 155 160
Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
165 170 175
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
180 185 190
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
195 200 205
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg Ser
210 215 220
Gly Gly Ser Ser Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
225 230 235 240
<210> 5
<211> 138
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 5
Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn
1 5 10 15
Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile
20 25 30
Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln
35 40 45
Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln
50 55 60
Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys
65 70 75 80
Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr
85 90 95
Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu
100 105 110
Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys
115 120 125
Arg Lys Arg Ser Gln Met Leu Phe Arg Gly
130 135
<210> 6
<211> 146
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 6
Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys
1 5 10 15
Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe
20 25 30
Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met
35 40 45
Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys
50 55 60
Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met
65 70 75 80
Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu
85 90 95
Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala
100 105 110
Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys
115 120 125
Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala
130 135 140
Ser Gln
145
<210> 7
<211> 166
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 7
Met Lys Tyr Thr Ser Tyr Ile Leu Ala Phe Gln Leu Cys Ile Val Leu
1 5 10 15
Gly Ser Leu Gly Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu
20 25 30
Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn
35 40 45
Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp
50 55 60
Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe
65 70 75 80
Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile
85 90 95
Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg
100 105 110
Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val
115 120 125
Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser
130 135 140
Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg
145 150 155 160
Gly Arg Arg Ala Ser Gln
165
<210> 8
<211> 220
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 8
Glu Met Gly Thr Ala Asp Leu Gly Pro Ser Ser Val Pro Thr Pro Thr
1 5 10 15
Asn Val Thr Ile Glu Ser Tyr Asn Met Asn Pro Ile Val Tyr Trp Glu
20 25 30
Tyr Gln Ile Met Pro Gln Val Pro Val Phe Thr Val Glu Val Lys Asn
35 40 45
Tyr Gly Val Lys Asn Ser Glu Trp Ile Asp Ala Cys Ile Asn Ile Ser
50 55 60
His His Tyr Cys Asn Ile Ser Asp His Val Gly Asp Pro Ser Asn Ser
65 70 75 80
Leu Trp Val Arg Val Lys Ala Arg Val Gly Gln Lys Glu Ser Ala Tyr
85 90 95
Ala Lys Ser Glu Glu Phe Ala Val Cys Arg Asp Gly Lys Ile Gly Pro
100 105 110
Pro Met Gly Thr Ala Asp Leu Gly Pro Ser Ser Val Pro Thr Pro Thr
115 120 125
Asn Val Thr Ile Glu Ser Tyr Asn Met Asn Pro Ile Val Tyr Trp Glu
130 135 140
Tyr Gln Ile Met Pro Gln Val Pro Val Phe Thr Val Glu Val Lys Asn
145 150 155 160
Tyr Gly Val Lys Asn Ser Glu Trp Ile Asp Ala Cys Ile Asn Ile Ser
165 170 175
His His Tyr Cys Asn Ile Ser Asp His Val Gly Asp Pro Ser Asn Ser
180 185 190
Leu Trp Val Arg Val Lys Ala Arg Val Gly Gln Lys Glu Ser Ala Tyr
195 200 205
Ala Lys Ser Glu Glu Phe Ala Val Cys Arg Asp Gly
210 215 220
<210> 9
<211> 229
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 9
Glu Met Gly Thr Ala Asp Leu Gly Pro Ser Ser Val Pro Thr Pro Thr
1 5 10 15
Asn Val Thr Ile Glu Ser Tyr Asn Met Asn Pro Ile Val Tyr Trp Glu
20 25 30
Tyr Gln Ile Met Pro Gln Val Pro Val Phe Thr Val Glu Val Lys Asn
35 40 45
Tyr Gly Val Lys Asn Ser Glu Trp Ile Asp Ala Cys Ile Asn Ile Ser
50 55 60
His His Tyr Cys Asn Ile Ser Asp His Val Gly Asp Pro Ser Asn Ser
65 70 75 80
Leu Trp Val Arg Val Lys Ala Arg Val Gly Gln Lys Glu Ser Ala Tyr
85 90 95
Ala Lys Ser Glu Glu Phe Ala Val Cys Arg Asp Gly Lys Ile Gly Pro
100 105 110
Pro Lys Leu Asp Ile Arg Lys Glu Glu Lys Gln Ile Met Ile Asp Ile
115 120 125
Phe His Pro Ser Val Phe Val Asn Gly Asp Glu Gln Glu Val Asp Tyr
130 135 140
Asp Pro Glu Thr Thr Cys Tyr Ile Arg Val Tyr Asn Val Tyr Val Arg
145 150 155 160
Met Asn Gly Ser Glu Ile Gln Tyr Lys Ile Leu Thr Gln Lys Glu Asp
165 170 175
Asp Cys Asp Glu Ile Gln Cys Gln Leu Ala Ile Pro Val Ser Ser Leu
180 185 190
Asn Ser Gln Tyr Cys Val Ser Ala Glu Gly Val Leu His Val Trp Gly
195 200 205
Val Thr Thr Glu Lys Ser Lys Glu Val Cys Ile Thr Ile Phe Asn Ser
210 215 220
Ser Ile Lys Gly Ser
225
<210> 10
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 10
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro Arg
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 11
<211> 113
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 11
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser
<210> 12
<211> 111
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 12
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser
20 25 30
Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro
35 40 45
Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
65 70 75 80
Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg
85 90 95
Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys
100 105 110
<210> 13
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 13
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 14
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 14
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu
225 230 235 240
Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln
245 250 255
Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val
260 265 270
Thr Ile Thr Cys Lys Ala Ser Glu Asn Val Asp Thr Tyr Val Ser Trp
275 280 285
Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala
290 295 300
Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser
305 310 315 320
Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe
325 330 335
Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr Asn Tyr Pro Phe Thr Phe Gly
340 345 350
Gln Gly Thr Lys Val Glu Val Lys Arg Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly
370 375 380
Ala Glu Leu Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala
385 390 395 400
Ser Gly Tyr Ile Phe Thr Ser Ser Trp Ile Asn Trp Val Lys Gln Ala
405 410 415
Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro Ser Asp Gly
420 425 430
Glu Val His Tyr Asn Gln Asp Phe Lys Asp Lys Ala Thr Leu Thr Val
435 440 445
Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser
450 455 460
Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Phe Leu Pro Trp Phe
465 470 475 480
Ala Asp Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490
<210> 15
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 15
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu
225 230 235 240
Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln
245 250 255
Leu Val Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ser Ser Val Lys
260 265 270
Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Ser Trp Ile Asn
275 280 285
Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile
290 295 300
Asp Pro Ser Asp Gly Glu Val His Tyr Asn Gln Asp Phe Lys Asp Lys
305 310 315 320
Ala Thr Leu Thr Val Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu
325 330 335
Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly
340 345 350
Phe Leu Pro Trp Phe Ala Asp Trp Gly Arg Gly Thr Leu Val Thr Val
355 360 365
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
370 375 380
Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val
385 390 395 400
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asn Val Asp Thr
405 410 415
Tyr Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
420 425 430
Ile Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser
435 440 445
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
450 455 460
Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr Asn Tyr Pro
465 470 475 480
Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg
485 490
<210> 16
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 16
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu
225 230 235 240
Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val
245 250 255
Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
260 265 270
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala
275 280 285
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly
290 295 300
Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly
305 310 315 320
Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp
325 330 335
Phe Ala Val Tyr Tyr Cys Gln Arg Ser Gly Gly Ser Ser Phe Thr Phe
340 345 350
Gly Pro Gly Thr Lys Val Asp Ile Lys Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly
370 375 380
Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly
385 390 395 400
Ser Gly Tyr Asn Phe Thr Ser Tyr Trp Ile Gly Trp Val Arg Gln Met
405 410 415
Pro Gly Lys Gly Leu Glu Leu Met Gly Ile Ile Tyr Pro Gly Asp Ser
420 425 430
Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala
435 440 445
Asp Lys Ser Ile Ser Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala
450 455 460
Ser Asp Thr Ala Met Tyr Tyr Cys Gly Ser Gly Ser Tyr Phe Tyr Phe
465 470 475 480
Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
485 490
<210> 17
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 17
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu
225 230 235 240
Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln
245 250 255
Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys
260 265 270
Ile Ser Cys Lys Gly Ser Gly Tyr Asn Phe Thr Ser Tyr Trp Ile Gly
275 280 285
Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Leu Met Gly Ile Ile
290 295 300
Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln
305 310 315 320
Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr Leu Gln Trp
325 330 335
Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Gly Ser Gly
340 345 350
Ser Tyr Phe Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val
355 360 365
Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
370 375 380
Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro
385 390 395 400
Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser
405 410 415
Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu
420 425 430
Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe
435 440 445
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu
450 455 460
Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg Ser Gly Gly Ser
465 470 475 480
Ser Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
485 490
<210> 18
<211> 380
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 18
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr
245 250 255
Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu
260 265 270
Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln
275 280 285
Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp
290 295 300
Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn
305 310 315 320
Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys
325 330 335
Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile
340 345 350
His Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr
355 360 365
Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg Gly
370 375 380
<210> 19
<211> 388
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 19
Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys
1 5 10 15
Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe
20 25 30
Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met
35 40 45
Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys
50 55 60
Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met
65 70 75 80
Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu
85 90 95
Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala
100 105 110
Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys
115 120 125
Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala
130 135 140
Ser Gln Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
145 150 155 160
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
165 170 175
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
180 185 190
Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser
195 200 205
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
210 215 220
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
225 230 235 240
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
245 250 255
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
260 265 270
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
275 280 285
Val Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val
290 295 300
Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
305 310 315 320
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
325 330 335
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
340 345 350
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
355 360 365
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
370 375 380
Ser Pro Gly Ala
385
<210> 20
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 20
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asn Val Asp Thr Tyr
20 25 30
Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr Asn Tyr Pro Phe
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ser Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Ser Trp Ile Asn Trp Val
145 150 155 160
Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro
165 170 175
Ser Asp Gly Glu Val His Tyr Asn Gln Asp Phe Lys Asp Lys Ala Thr
180 185 190
Leu Thr Val Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser
195 200 205
Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Phe Leu
210 215 220
Pro Trp Phe Ala Asp Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys
260 265 270
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu
275 280 285
Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu
290 295 300
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
305 310 315 320
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
325 330 335
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
340 345 350
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
355 360 365
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
370 375 380
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser
385 390 395 400
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys
405 410 415
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
420 425 430
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
435 440 445
Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
450 455 460
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
465 470 475 480
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
485 490
<210> 21
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 21
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Ser
20 25 30
Trp Ile Asn Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Arg Ile Asp Pro Ser Asp Gly Glu Val His Tyr Asn Gln Asp Phe
50 55 60
Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Thr Asn Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Phe Leu Pro Trp Phe Ala Asp Trp Gly Arg Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser
130 135 140
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asn
145 150 155 160
Val Asp Thr Tyr Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro
165 170 175
Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser
180 185 190
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
195 200 205
Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr
210 215 220
Asn Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys
260 265 270
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu
275 280 285
Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu
290 295 300
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
305 310 315 320
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
325 330 335
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
340 345 350
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
355 360 365
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
370 375 380
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser
385 390 395 400
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys
405 410 415
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
420 425 430
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
435 440 445
Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
450 455 460
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
465 470 475 480
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
485 490
<210> 22
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 22
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg Ser Gly Gly Ser Ser
85 90 95
Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser
130 135 140
Cys Lys Gly Ser Gly Tyr Asn Phe Thr Ser Tyr Trp Ile Gly Trp Val
145 150 155 160
Arg Gln Met Pro Gly Lys Gly Leu Glu Leu Met Gly Ile Ile Tyr Pro
165 170 175
Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr
180 185 190
Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr Leu Gln Trp Ser Ser
195 200 205
Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Gly Ser Gly Ser Tyr
210 215 220
Phe Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys
260 265 270
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu
275 280 285
Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu
290 295 300
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
305 310 315 320
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
325 330 335
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
340 345 350
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
355 360 365
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
370 375 380
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser
385 390 395 400
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys
405 410 415
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
420 425 430
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
435 440 445
Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
450 455 460
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
465 470 475 480
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
485 490
<210> 23
<211> 493
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 23
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu
1 5 10 15
Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Asn Phe Thr Ser Tyr
20 25 30
Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Leu Met
35 40 45
Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe
50 55 60
Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr
65 70 75 80
Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Gly Ser Gly Ser Tyr Phe Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu
100 105 110
Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
115 120 125
Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
130 135 140
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
145 150 155 160
Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
165 170 175
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
180 185 190
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
195 200 205
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg Ser
210 215 220
Gly Gly Ser Ser Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys
225 230 235 240
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg
245 250 255
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys
260 265 270
Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu
275 280 285
Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu
290 295 300
Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys
305 310 315 320
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
325 330 335
Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu
340 345 350
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
355 360 365
Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys
370 375 380
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser
385 390 395 400
Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys
405 410 415
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
420 425 430
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
435 440 445
Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln
450 455 460
Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
465 470 475 480
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
485 490
<210> 24
<211> 379
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 24
Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn
1 5 10 15
Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile
20 25 30
Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln
35 40 45
Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln
50 55 60
Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys
65 70 75 80
Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr
85 90 95
Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu
100 105 110
Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys
115 120 125
Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Gly Gly Gly Ser Gly Gly
130 135 140
Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro
145 150 155 160
Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro
165 170 175
Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr
180 185 190
Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn
195 200 205
Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg
210 215 220
Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val
225 230 235 240
Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser
245 250 255
Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
260 265 270
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Glu
275 280 285
Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe
290 295 300
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
305 310 315 320
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
325 330 335
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
340 345 350
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
355 360 365
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
370 375
<210> 25
<211> 388
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 25
Cys Tyr Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys
1 5 10 15
Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe
20 25 30
Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met
35 40 45
Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys
50 55 60
Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met
65 70 75 80
Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu
85 90 95
Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala
100 105 110
Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys
115 120 125
Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala
130 135 140
Ser Gln Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
145 150 155 160
Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala
165 170 175
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
180 185 190
Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser
195 200 205
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
210 215 220
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
225 230 235 240
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
245 250 255
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
260 265 270
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
275 280 285
Val Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val
290 295 300
Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
305 310 315 320
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
325 330 335
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
340 345 350
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
355 360 365
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
370 375 380
Ser Pro Gly Lys
385
<210> 26
<211> 13
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 26
Gly Gly Ser Leu Ser Gly Arg Ser Asp Asn His Gly Ser
1 5 10
<210> 27
<211> 42
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 27
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ile
1 5 10 15
Ser Ser Gly Leu Leu Ser Ser Gly Gly Ser Gly Gly Ser Leu Ser Gly
20 25 30
Arg Ser Asp Asn His Gly Gly Gly Gly Ser
35 40
<210> 28
<211> 6
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 28
Gly Pro Leu Gly Val Arg
1 5
<210> 29
<211> 7
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 29
Pro Leu Gly Met Trp Ser Arg
1 5
<210> 30
<211> 7
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 30
Pro Leu Gly Leu Trp Ala Arg
1 5
<210> 31
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 31
Pro Gln Gly Ile Ala Gly Gln Arg
1 5
<210> 32
<211> 6
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 32
Pro Leu Gly Leu Ala Gly
1 5
<210> 33
<211> 6
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 33
Leu Ala Leu Gly Pro Arg
1 5
<210> 34
<211> 10
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 34
Gly Gly Pro Leu Gly Met Leu Ser Gln Ser
1 5 10
<210> 35
<211> 9
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 35
Gly Gly Gly Gly Arg Arg Gly Gly Ser
1 5
<210> 36
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 36
Thr Gly Arg Gly Pro Ser Trp Val
1 5
<210> 37
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 37
Ser Ala Arg Gly Pro Ser Arg Trp
1 5
<210> 38
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 38
Thr Ala Arg Gly Pro Ser Phe Lys
1 5
<210> 39
<211> 7
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 39
Thr Ala Arg Gly Pro Ser Trp
1 5
<210> 40
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 40
Gly Gly Trp His Thr Gly Arg Asn
1 5
<210> 41
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 41
His Thr Gly Arg Ser Gly Ala Leu
1 5
<210> 42
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 42
Pro Leu Thr Gly Arg Ser Gly Gly
1 5
<210> 43
<211> 7
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 43
Leu Thr Gly Arg Ser Gly Ala
1 5
<210> 44
<211> 8
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 44
Arg Gln Ala Arg Val Val Asn Gly
1 5
<210> 45
<211> 18
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 45
Val His Met Pro Leu Gly Phe Leu Gly Pro Arg Gln Ala Arg Val Val
1 5 10 15
Asn Gly
<210> 46
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 46
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Ser Ser Asn Trp Pro Arg
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 47
<211> 706
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 47
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly
450 455 460
Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser
465 470 475 480
Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Glu Asn Val Asp
485 490 495
Thr Tyr Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu
500 505 510
Leu Ile Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe
515 520 525
Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu
530 535 540
Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr Asn Tyr
545 550 555 560
Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Val Lys Arg Gly Gly
565 570 575
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln
580 585 590
Leu Val Gln Ser Gly Ala Glu Leu Lys Lys Pro Gly Ser Ser Val Lys
595 600 605
Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser Ser Trp Ile Asn
610 615 620
Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile
625 630 635 640
Asp Pro Ser Asp Gly Glu Val His Tyr Asn Gln Asp Phe Lys Asp Lys
645 650 655
Ala Thr Leu Thr Val Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu
660 665 670
Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly
675 680 685
Phe Leu Pro Trp Phe Ala Asp Trp Gly Gln Gly Thr Leu Val Thr Val
690 695 700
Ser Ser
705
<210> 48
<211> 706
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 48
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly
450 455 460
Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Leu Lys Lys Pro
465 470 475 480
Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr
485 490 495
Ser Ser Trp Ile Asn Trp Val Lys Gln Ala Pro Gly Gln Gly Leu Glu
500 505 510
Trp Ile Gly Arg Ile Asp Pro Ser Asp Gly Glu Val His Tyr Asn Gln
515 520 525
Asp Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Thr Asn Thr
530 535 540
Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr
545 550 555 560
Tyr Cys Ala Arg Gly Phe Leu Pro Trp Phe Ala Asp Trp Gly Arg Gly
565 570 575
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
580 585 590
Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Thr
595 600 605
Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser
610 615 620
Glu Asn Val Asp Thr Tyr Val Ser Trp Tyr Gln Gln Lys Pro Gly Lys
625 630 635 640
Ala Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg Tyr Thr Gly Val
645 650 655
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
660 665 670
Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys Gly Gln
675 680 685
Ser Tyr Asn Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys Val Glu Val
690 695 700
Lys Arg
705
<210> 49
<211> 706
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 49
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly
450 455 460
Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser
465 470 475 480
Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser
485 490 495
Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg
500 505 510
Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg
515 520 525
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg
530 535 540
Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Arg Ser Gly Gly
545 550 555 560
Ser Ser Phe Thr Phe Gly Pro Gly Thr Lys Val Asp Ile Lys Gly Gly
565 570 575
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln
580 585 590
Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys
595 600 605
Ile Ser Cys Lys Gly Ser Gly Tyr Asn Phe Thr Ser Tyr Trp Ile Gly
610 615 620
Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu Leu Met Gly Ile Ile
625 630 635 640
Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln
645 650 655
Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr Ala Tyr Leu Gln Trp
660 665 670
Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr Tyr Cys Gly Ser Gly
675 680 685
Ser Tyr Phe Tyr Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val
690 695 700
Ser Ser
705
<210> 50
<211> 706
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 50
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly
450 455 460
Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro
465 470 475 480
Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Asn Phe Thr
485 490 495
Ser Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly Leu Glu
500 505 510
Leu Met Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr Ser Pro
515 520 525
Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile Ser Thr
530 535 540
Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala Met Tyr
545 550 555 560
Tyr Cys Gly Ser Gly Ser Tyr Phe Tyr Phe Asp Leu Trp Gly Arg Gly
565 570 575
Thr Leu Val Thr Val Ser Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
580 585 590
Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr
595 600 605
Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser
610 615 620
Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly
625 630 635 640
Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly
645 650 655
Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu
660 665 670
Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln
675 680 685
Arg Ser Gly Gly Ser Ser Phe Thr Phe Gly Pro Gly Thr Lys Val Asp
690 695 700
Ile Lys
705
<210> 51
<211> 593
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 51
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Gly Gly Gly Ser Gln Asp Pro Tyr Val Lys Glu Ala Glu
450 455 460
Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val Ala Asp Asn
465 470 475 480
Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp
485 490 495
Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe
500 505 510
Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val Glu Thr Ile
515 520 525
Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg
530 535 540
Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp Leu Asn Val
545 550 555 560
Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala Glu Leu Ser
565 570 575
Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met Leu Phe Arg
580 585 590
Gly
<210> 52
<211> 601
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 52
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Gly Gly Gly Ser Cys Tyr Cys Gln Asp Pro Tyr Val Lys
450 455 460
Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly His Ser Asp Val
465 470 475 480
Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys Asn Trp Lys Glu
485 490 495
Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val Ser Phe Tyr Phe
500 505 510
Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile Gln Lys Ser Val
515 520 525
Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe Asn Ser Asn Lys
530 535 540
Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr Ser Val Thr Asp
545 550 555 560
Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile Gln Val Met Ala
565 570 575
Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg Lys Arg Ser Gln Met
580 585 590
Leu Phe Arg Gly Arg Arg Ala Ser Gln
595 600
<210> 53
<211> 218
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 53
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Lys Gly Val Ser Thr Ser
20 25 30
Gly Tyr Ser Tyr Leu His Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro
35 40 45
Arg Leu Leu Ile Tyr Leu Ala Ser Tyr Leu Glu Ser Gly Val Pro Ala
50 55 60
Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser
65 70 75 80
Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln His Ser Arg
85 90 95
Asp Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105 110
Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln
115 120 125
Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr
130 135 140
Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser
145 150 155 160
Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr
165 170 175
Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys
180 185 190
His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro
195 200 205
Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
210 215
<210> 54
<211> 713
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 54
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
450 455 460
Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser
465 470 475 480
Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys
485 490 495
Lys Ala Ser Glu Asn Val Asp Thr Tyr Val Ser Trp Tyr Gln Gln Lys
500 505 510
Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala Ser Asn Arg Tyr
515 520 525
Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
530 535 540
Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr
545 550 555 560
Cys Gly Gln Ser Tyr Asn Tyr Pro Phe Thr Phe Gly Gln Gly Thr Lys
565 570 575
Val Glu Val Lys Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
580 585 590
Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Leu Lys
595 600 605
Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile
610 615 620
Phe Thr Ser Ser Trp Ile Asn Trp Val Lys Gln Ala Pro Gly Gln Gly
625 630 635 640
Leu Glu Trp Ile Gly Arg Ile Asp Pro Ser Asp Gly Glu Val His Tyr
645 650 655
Asn Gln Asp Phe Lys Asp Lys Ala Thr Leu Thr Val Asp Lys Ser Thr
660 665 670
Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala
675 680 685
Val Tyr Tyr Cys Ala Arg Gly Phe Leu Pro Trp Phe Ala Asp Trp Gly
690 695 700
Gln Gly Thr Leu Val Thr Val Ser Ser
705 710
<210> 55
<211> 713
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 55
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
450 455 460
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser
465 470 475 480
Gly Ala Glu Leu Lys Lys Pro Gly Ser Ser Val Lys Val Ser Cys Lys
485 490 495
Ala Ser Gly Tyr Ile Phe Thr Ser Ser Trp Ile Asn Trp Val Lys Gln
500 505 510
Ala Pro Gly Gln Gly Leu Glu Trp Ile Gly Arg Ile Asp Pro Ser Asp
515 520 525
Gly Glu Val His Tyr Asn Gln Asp Phe Lys Asp Lys Ala Thr Leu Thr
530 535 540
Val Asp Lys Ser Thr Asn Thr Ala Tyr Met Glu Leu Ser Ser Leu Arg
545 550 555 560
Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Gly Phe Leu Pro Trp
565 570 575
Phe Ala Asp Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly Gly
580 585 590
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln
595 600 605
Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly Asp Arg Val
610 615 620
Thr Ile Thr Cys Lys Ala Ser Glu Asn Val Asp Thr Tyr Val Ser Trp
625 630 635 640
Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Gly Ala
645 650 655
Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser
660 665 670
Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe
675 680 685
Ala Thr Tyr Tyr Cys Gly Gln Ser Tyr Asn Tyr Pro Phe Thr Phe Gly
690 695 700
Gln Gly Thr Lys Val Glu Val Lys Arg
705 710
<210> 56
<211> 713
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 56
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
450 455 460
Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser
465 470 475 480
Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys
485 490 495
Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln
500 505 510
Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg
515 520 525
Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
530 535 540
Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr
545 550 555 560
Tyr Cys Gln Arg Ser Gly Gly Ser Ser Phe Thr Phe Gly Pro Gly Thr
565 570 575
Lys Val Asp Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
580 585 590
Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
595 600 605
Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys Gly Ser Gly Tyr Asn
610 615 620
Phe Thr Ser Tyr Trp Ile Gly Trp Val Arg Gln Met Pro Gly Lys Gly
625 630 635 640
Leu Glu Leu Met Gly Ile Ile Tyr Pro Gly Asp Ser Asp Thr Arg Tyr
645 650 655
Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser Ala Asp Lys Ser Ile
660 665 670
Ser Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys Ala Ser Asp Thr Ala
675 680 685
Met Tyr Tyr Cys Gly Ser Gly Ser Tyr Phe Tyr Phe Asp Leu Trp Gly
690 695 700
Arg Gly Thr Leu Val Thr Val Ser Ser
705 710
<210> 57
<211> 713
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 57
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
450 455 460
Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Val Gln Leu Val Gln Ser
465 470 475 480
Gly Ala Glu Val Lys Lys Pro Gly Glu Ser Leu Lys Ile Ser Cys Lys
485 490 495
Gly Ser Gly Tyr Asn Phe Thr Ser Tyr Trp Ile Gly Trp Val Arg Gln
500 505 510
Met Pro Gly Lys Gly Leu Glu Leu Met Gly Ile Ile Tyr Pro Gly Asp
515 520 525
Ser Asp Thr Arg Tyr Ser Pro Ser Phe Gln Gly Gln Val Thr Ile Ser
530 535 540
Ala Asp Lys Ser Ile Ser Thr Ala Tyr Leu Gln Trp Ser Ser Leu Lys
545 550 555 560
Ala Ser Asp Thr Ala Met Tyr Tyr Cys Gly Ser Gly Ser Tyr Phe Tyr
565 570 575
Phe Asp Leu Trp Gly Arg Gly Thr Leu Val Thr Val Ser Ser Gly Gly
580 585 590
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val
595 600 605
Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
610 615 620
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Ser Tyr Leu Ala
625 630 635 640
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly
645 650 655
Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly
660 665 670
Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp
675 680 685
Phe Ala Val Tyr Tyr Cys Gln Arg Ser Gly Gly Ser Ser Phe Thr Phe
690 695 700
Gly Pro Gly Thr Lys Val Asp Ile Lys
705 710
<210> 58
<211> 600
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 58
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Asp
450 455 460
Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe Asn Ala Gly
465 470 475 480
His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly Ile Leu Lys
485 490 495
Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser Gln Ile Val
500 505 510
Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp Gln Ser Ile
515 520 525
Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val Lys Phe Phe
530 535 540
Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu Thr Asn Tyr
545 550 555 560
Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His Glu Leu Ile
565 570 575
Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly Lys Arg Lys
580 585 590
Arg Ser Gln Met Leu Phe Arg Gly
595 600
<210> 59
<211> 608
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 59
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Tyr
450 455 460
Cys Gln Asp Pro Tyr Val Lys Glu Ala Glu Asn Leu Lys Lys Tyr Phe
465 470 475 480
Asn Ala Gly His Ser Asp Val Ala Asp Asn Gly Thr Leu Phe Leu Gly
485 490 495
Ile Leu Lys Asn Trp Lys Glu Glu Ser Asp Arg Lys Ile Met Gln Ser
500 505 510
Gln Ile Val Ser Phe Tyr Phe Lys Leu Phe Lys Asn Phe Lys Asp Asp
515 520 525
Gln Ser Ile Gln Lys Ser Val Glu Thr Ile Lys Glu Asp Met Asn Val
530 535 540
Lys Phe Phe Asn Ser Asn Lys Lys Lys Arg Asp Asp Phe Glu Lys Leu
545 550 555 560
Thr Asn Tyr Ser Val Thr Asp Leu Asn Val Gln Arg Lys Ala Ile His
565 570 575
Glu Leu Ile Gln Val Met Ala Glu Leu Ser Pro Ala Ala Lys Thr Gly
580 585 590
Lys Arg Lys Arg Ser Gln Met Leu Phe Arg Gly Arg Arg Ala Ser Gln
595 600 605
<210> 60
<211> 239
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 60
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val
165 170 175
Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile
210 215 220
Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
225 230 235
<210> 61
<211> 234
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 61
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr
115 120 125
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile
130 135 140
Thr Cys Arg Ala Ser Gln Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met
145 150 155 160
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile Ser
165 170 175
Tyr Ala Ser Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Gln His Ser Trp Gly Ile Pro Arg Thr
210 215 220
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
225 230
<210> 62
<211> 116
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 62
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Ser Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Leu Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Pro Ile Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val
100 105 110
Thr Val Ser Ser
115
<210> 63
<211> 112
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 63
Gln Ser Val Leu Thr Gln Pro Pro Ser Val Ser Gly Ala Pro Gly Gln
1 5 10 15
Arg Val Thr Ile Ser Cys Ser Gly Ser Ser Ser Asn Ile Gly Ser Asn
20 25 30
Tyr Val Ser Trp Tyr Gln Gln Leu Pro Gly Thr Ala Pro Lys Leu Leu
35 40 45
Ile Tyr Asp Asn Asn Gln Arg Pro Ser Gly Val Pro Asp Arg Phe Ser
50 55 60
Gly Ser Lys Ser Gly Thr Ser Ala Ser Leu Ala Ile Thr Gly Leu Gln
65 70 75 80
Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Gln Ser Asn Asp Ala Ser Leu
85 90 95
Val Glu Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro
100 105 110
<210> 64
<211> 119
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 64
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 Phe Thr Phe Ser Ser Tyr
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly 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 Arg Tyr Tyr Ser Phe Tyr Thr Ser Phe Asp Tyr Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 65
<211> 165
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 65
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu
165
<210> 66
<211> 165
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 66
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu
165
<210> 67
<211> 492
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 67
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu
225 230 235 240
Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val
245 250 255
Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
260 265 270
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala
275 280 285
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly
290 295 300
Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly
305 310 315 320
Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp
325 330 335
Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe
340 345 350
Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly
370 375 380
Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala
385 390 395 400
Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val Arg Gln Ala
405 410 415
Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val Tyr Asn Gly
420 425 430
Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Thr
435 440 445
Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser Leu Arg Ser
450 455 460
Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile Ala Ala Gly
465 470 475 480
Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
485 490
<210> 68
<211> 499
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 68
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Val His Met Pro Leu Gly Phe Leu
225 230 235 240
Gly Pro Arg Gln Ala Arg Val Val Asn Ala Gly Gly Gly Gly Ser Gly
245 250 255
Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
260 265 270
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
275 280 285
Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
290 295 300
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
305 310 315 320
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
325 330 335
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr
340 345 350
Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
355 360 365
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
370 375 380
Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser
385 390 395 400
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser
405 410 415
Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
420 425 430
Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln
435 440 445
Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu
450 455 460
Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala
465 470 475 480
Arg Asp Pro Ile Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr
485 490 495
Val Ser Ser
<210> 69
<211> 487
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 69
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu
225 230 235 240
Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val
245 250 255
Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala
260 265 270
Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala
275 280 285
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly
290 295 300
Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly
305 310 315 320
Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp
325 330 335
Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe
340 345 350
Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly
355 360 365
Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro
370 375 380
Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg
385 390 395 400
Ala Ser Gln Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met His Trp Tyr
405 410 415
Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile Ser Tyr Ala Ser
420 425 430
Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly
435 440 445
Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala
450 455 460
Thr Tyr Tyr Cys Gln His Ser Trp Gly Ile Pro Arg Thr Phe Gly Gln
465 470 475 480
Gly Thr Lys Val Glu Ile Lys
485
<210> 70
<211> 494
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 70
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Val His Met Pro Leu Gly Phe Leu
225 230 235 240
Gly Pro Arg Gln Ala Arg Val Val Asn Ala Gly Gly Gly Gly Ser Gly
245 250 255
Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
260 265 270
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
275 280 285
Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
290 295 300
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
305 310 315 320
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
325 330 335
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr
340 345 350
Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
355 360 365
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp
370 375 380
Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp
385 390 395 400
Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Val Ser Thr Ser Ser
405 410 415
Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys
420 425 430
Val Leu Ile Ser Tyr Ala Ser Asn Leu Glu Ser Gly Val Pro Ser Arg
435 440 445
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser
450 455 460
Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Ser Trp Gly
465 470 475 480
Ile Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
485 490
<210> 71
<211> 407
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 71
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr
245 250 255
Leu Met Leu Leu Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu
260 265 270
Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln
275 280 285
Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln
290 295 300
Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu
305 310 315 320
Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp
325 330 335
Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu
340 345 350
Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile
355 360 365
Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val
370 375 380
Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln
385 390 395 400
Glu Ser Leu Arg Ser Lys Glu
405
<210> 72
<211> 407
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 72
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
1 5 10 15
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
20 25 30
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
35 40 45
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
50 55 60
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
65 70 75 80
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
85 90 95
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
100 105 110
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
115 120 125
Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys Asn Gln Val Ser
130 135 140
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
145 150 155 160
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
165 170 175
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
180 185 190
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
195 200 205
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
210 215 220
Pro Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
225 230 235 240
Gly Ser Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr
245 250 255
Leu Met Leu Leu Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu
260 265 270
Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln
275 280 285
Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln
290 295 300
Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu
305 310 315 320
Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp
325 330 335
Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu
340 345 350
Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile
355 360 365
Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val
370 375 380
Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln
385 390 395 400
Glu Ser Leu Arg Ser Lys Glu
405
<210> 73
<211> 492
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 73
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val
165 170 175
Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile
210 215 220
Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
245 250 255
Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro
260 265 270
Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe
275 280 285
Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val
290 295 300
Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe
305 310 315 320
Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro
325 330 335
Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr
340 345 350
Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val
355 360 365
Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala
370 375 380
Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg
385 390 395 400
Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly
405 410 415
Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro
420 425 430
Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser
435 440 445
Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln
450 455 460
Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His
465 470 475 480
Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
485 490
<210> 74
<211> 499
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 74
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
115 120 125
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
130 135 140
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val
145 150 155 160
Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val
165 170 175
Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
180 185 190
Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser
195 200 205
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile
210 215 220
Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Gly
225 230 235 240
Gly Gly Gly Ser Val His Met Pro Leu Gly Phe Leu Gly Pro Arg Gln
245 250 255
Ala Arg Val Val Asn Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
260 265 270
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
275 280 285
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr
290 295 300
Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
305 310 315 320
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
325 330 335
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
340 345 350
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
355 360 365
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
370 375 380
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
385 390 395 400
Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser
405 410 415
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
420 425 430
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
435 440 445
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
450 455 460
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
465 470 475 480
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
485 490 495
Pro Gly Lys
<210> 75
<211> 487
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 75
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr
115 120 125
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile
130 135 140
Thr Cys Arg Ala Ser Gln Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met
145 150 155 160
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile Ser
165 170 175
Tyr Ala Ser Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Gln His Ser Trp Gly Ile Pro Arg Thr
210 215 220
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly
225 230 235 240
Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly
245 250 255
Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
260 265 270
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
275 280 285
Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val
290 295 300
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
305 310 315 320
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
325 330 335
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
340 345 350
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
355 360 365
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
370 375 380
Glu Pro Gln Val Cys Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys
385 390 395 400
Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp
405 410 415
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
420 425 430
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser
435 440 445
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
450 455 460
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
465 470 475 480
Leu Ser Leu Ser Pro Gly Lys
485
<210> 76
<211> 494
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 76
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
20 25 30
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
35 40 45
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
50 55 60
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
65 70 75 80
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
85 90 95
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
100 105 110
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr
115 120 125
Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile
130 135 140
Thr Cys Arg Ala Ser Gln Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met
145 150 155 160
His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile Ser
165 170 175
Tyr Ala Ser Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser
180 185 190
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu
195 200 205
Asp Phe Ala Thr Tyr Tyr Cys Gln His Ser Trp Gly Ile Pro Arg Thr
210 215 220
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Val
225 230 235 240
His Met Pro Leu Gly Phe Leu Gly Pro Arg Gln Ala Arg Val Val Asn
245 250 255
Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Lys Thr His Thr
260 265 270
Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe
275 280 285
Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro
290 295 300
Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro Glu Val
305 310 315 320
Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr
325 330 335
Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val
340 345 350
Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys
355 360 365
Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser
370 375 380
Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Cys Thr Leu Pro Pro
385 390 395 400
Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val
405 410 415
Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly
420 425 430
Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp
435 440 445
Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp
450 455 460
Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His
465 470 475 480
Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
485 490
<210> 77
<211> 407
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 77
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
165 170 175
Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
180 185 190
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
195 200 205
Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val
210 215 220
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
225 230 235 240
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
245 250 255
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
260 265 270
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
275 280 285
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
290 295 300
Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys
305 310 315 320
Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
325 330 335
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
340 345 350
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
355 360 365
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
370 375 380
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
385 390 395 400
Leu Ser Leu Ser Pro Gly Lys
405
<210> 78
<211> 407
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 78
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
165 170 175
Gly Gly Gly Ser Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
180 185 190
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
195 200 205
Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val
210 215 220
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
225 230 235 240
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
245 250 255
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
260 265 270
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
275 280 285
Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
290 295 300
Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys Arg Glu Glu Met Thr Lys
305 310 315 320
Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
325 330 335
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
340 345 350
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
355 360 365
Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser
370 375 380
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
385 390 395 400
Leu Ser Leu Ser Pro Gly Lys
405
<210> 79
<211> 705
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 79
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly
450 455 460
Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser
465 470 475 480
Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser
485 490 495
Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg
500 505 510
Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg
515 520 525
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg
530 535 540
Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser
545 550 555 560
Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly
565 570 575
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln
580 585 590
Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys
595 600 605
Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser
610 615 620
Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile
625 630 635 640
Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg
645 650 655
Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu
660 665 670
Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp
675 680 685
Pro Ile Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
690 695 700
Ser
705
<210> 80
<211> 694
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 80
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly
450 455 460
Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala
465 470 475 480
Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro
485 490 495
Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr
500 505 510
Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
515 520 525
Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys
530 535 540
Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val
545 550 555 560
Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
565 570 575
Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro
580 585 590
Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
595 600 605
Ser Tyr Ser Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu
610 615 620
Trp Met Gly Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala Gln
625 630 635 640
Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr
645 650 655
Ala Tyr Leu Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr
660 665 670
Tyr Cys Ala Arg Asp Pro Ile Ala Ala Gly Tyr Trp Gly Gln Gly Thr
675 680 685
Leu Val Thr Val Ser Ser
690
<210> 81
<211> 700
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 81
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Pro Leu Gly Val Arg Gly Gly Gly Gly Ser Gly Gly Gly
450 455 460
Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser
465 470 475 480
Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser
485 490 495
Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg
500 505 510
Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg
515 520 525
Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg
530 535 540
Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser
545 550 555 560
Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly
565 570 575
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln
580 585 590
Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val
595 600 605
Thr Ile Thr Cys Arg Ala Ser Gln Ser Val Ser Thr Ser Ser Tyr Ser
610 615 620
Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu
625 630 635 640
Ile Ser Tyr Ala Ser Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser
645 650 655
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln
660 665 670
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His Ser Trp Gly Ile Pro
675 680 685
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
690 695 700
<210> 82
<211> 689
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 82
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly
450 455 460
Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala
465 470 475 480
Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro
485 490 495
Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr
500 505 510
Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
515 520 525
Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys
530 535 540
Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val
545 550 555 560
Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
565 570 575
Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser
580 585 590
Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Val Ser
595 600 605
Thr Ser Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro Gly Lys
610 615 620
Ala Pro Lys Val Leu Ile Ser Tyr Ala Ser Asn Leu Glu Ser Gly Val
625 630 635 640
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
645 650 655
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His
660 665 670
Ser Trp Gly Ile Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile
675 680 685
Lys
<210> 83
<211> 620
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 83
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Gly Gly Gly Ser Cys Asp Leu Pro Gln Thr His Ser Leu
450 455 460
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Lys Ile Ser
465 470 475 480
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
485 490 495
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
500 505 510
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
515 520 525
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
530 535 540
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
545 550 555 560
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
565 570 575
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
580 585 590
Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu
595 600 605
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
610 615 620
<210> 84
<211> 620
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 84
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Asp Cys Lys Ala Ser Gly Ile Thr Phe Ser Asn Ser
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Tyr Asp Gly Ser Lys Arg Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Phe
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Asn Asp Asp Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser
115 120 125
Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp
130 135 140
Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr
145 150 155 160
Ser Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr
165 170 175
Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys
180 185 190
Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp
195 200 205
Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala
210 215 220
Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro
225 230 235 240
Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val
245 250 255
Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val
260 265 270
Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln
275 280 285
Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln
290 295 300
Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly
305 310 315 320
Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro
325 330 335
Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr
340 345 350
Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser
355 360 365
Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr
370 375 380
Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr
385 390 395 400
Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe
405 410 415
Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys
420 425 430
Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly Gly Ser Gly Gly Gly
435 440 445
Gly Ser Gly Gly Gly Gly Ser Cys Asp Leu Pro Gln Thr His Ser Leu
450 455 460
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Lys Ile Ser
465 470 475 480
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
485 490 495
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
500 505 510
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
515 520 525
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
530 535 540
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
545 550 555 560
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
565 570 575
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
580 585 590
Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu
595 600 605
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
610 615 620
<210> 85
<211> 712
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 85
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
450 455 460
Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser
465 470 475 480
Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys
485 490 495
Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln
500 505 510
Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg
515 520 525
Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
530 535 540
Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr
545 550 555 560
Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr
565 570 575
Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
580 585 590
Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys
595 600 605
Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr
610 615 620
Phe Thr Ser Tyr Ser Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly
625 630 635 640
Leu Glu Trp Met Gly Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr
645 650 655
Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr
660 665 670
Ser Thr Ala Tyr Leu Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala
675 680 685
Val Tyr Tyr Cys Ala Arg Asp Pro Ile Ala Ala Gly Tyr Trp Gly Gln
690 695 700
Gly Thr Leu Val Thr Val Ser Ser
705 710
<210> 86
<211> 701
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 86
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile
450 455 460
Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg
465 470 475 480
Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu
485 490 495
Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
500 505 510
Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser
515 520 525
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu
530 535 540
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr
545 550 555 560
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly
565 570 575
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser
580 585 590
Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys
595 600 605
Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val Arg Gln
610 615 620
Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val Tyr Asn
625 630 635 640
Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr
645 650 655
Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser Leu Arg
660 665 670
Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile Ala Ala
675 680 685
Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
690 695 700
<210> 87
<211> 707
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 87
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly
450 455 460
Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser
465 470 475 480
Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys
485 490 495
Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln
500 505 510
Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg
515 520 525
Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp
530 535 540
Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr
545 550 555 560
Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr
565 570 575
Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
580 585 590
Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser
595 600 605
Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser
610 615 620
Val Ser Thr Ser Ser Tyr Ser Tyr Met His Trp Tyr Gln Gln Lys Pro
625 630 635 640
Gly Lys Ala Pro Lys Val Leu Ile Ser Tyr Ala Ser Asn Leu Glu Ser
645 650 655
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
660 665 670
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
675 680 685
Gln His Ser Trp Gly Ile Pro Arg Thr Phe Gly Gln Gly Thr Lys Val
690 695 700
Glu Ile Lys
705
<210> 88
<211> 696
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 88
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile
450 455 460
Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg
465 470 475 480
Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu
485 490 495
Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
500 505 510
Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser
515 520 525
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu
530 535 540
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr
545 550 555 560
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly
565 570 575
Gly Gly Gly Ser Gly Gly Gly Gly Ser Asp Ile Gln Met Thr Gln Ser
580 585 590
Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys
595 600 605
Arg Ala Ser Gln Ser Val Ser Thr Ser Ser Tyr Ser Tyr Met His Trp
610 615 620
Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Val Leu Ile Ser Tyr Ala
625 630 635 640
Ser Asn Leu Glu Ser Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser
645 650 655
Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe
660 665 670
Ala Thr Tyr Tyr Cys Gln His Ser Trp Gly Ile Pro Arg Thr Phe Gly
675 680 685
Gln Gly Thr Lys Val Glu Ile Lys
690 695
<210> 89
<211> 627
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 89
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Asp
450 455 460
Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu
465 470 475 480
Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His
485 490 495
Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala
500 505 510
Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu
515 520 525
Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp
530 535 540
Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys
545 550 555 560
Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp
565 570 575
Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu
580 585 590
Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala Glu
595 600 605
Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg
610 615 620
Ser Lys Glu
625
<210> 90
<211> 627
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 90
Gln Val Gln Leu Val Gln Ser Gly Val Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr
20 25 30
Tyr Met Tyr Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Gly Ile Asn Pro Ser Asn Gly Gly Thr Asn Phe Asn Glu Lys Phe
50 55 60
Lys Asn Arg Val Thr Leu Thr Thr Asp Ser Ser Thr Thr Thr Ala Tyr
65 70 75 80
Met Glu Leu Lys Ser Leu Gln Phe Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Arg Asp Tyr Arg Phe Asp Met Gly Phe Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro
210 215 220
Pro Cys Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val
225 230 235 240
Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr
245 250 255
Pro Glu Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu
260 265 270
Val Gln Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys
275 280 285
Thr Lys Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser
290 295 300
Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys
305 310 315 320
Cys Lys Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile
325 330 335
Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro
340 345 350
Pro Ser Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu
355 360 365
Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn
370 375 380
Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser
385 390 395 400
Asp Gly Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg
405 410 415
Trp Gln Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu
420 425 430
His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly
435 440 445
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Asp
450 455 460
Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu
465 470 475 480
Ala Gln Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His
485 490 495
Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala
500 505 510
Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu
515 520 525
Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp
530 535 540
Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys
545 550 555 560
Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp
565 570 575
Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu
580 585 590
Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala Glu
595 600 605
Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg
610 615 620
Ser Lys Glu
625
<210> 91
<211> 449
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 91
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 Phe Asp Phe Ser Arg Tyr
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu
50 55 60
Lys Asp Lys Phe Ile 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<210> 92
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 92
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 93
<211> 452
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 93
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Asn Ser Phe
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Gly Gly 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 Phe Cys
85 90 95
Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Lys
450
<210> 94
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 94
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 95
<211> 450
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 95
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Ala Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Trp Met Gln Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Tyr Pro Gly Asp Gly Asp Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Lys Thr Val Tyr
65 70 75 80
Met His Leu Ser Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Asp Tyr Tyr Gly Ser Asn Ser Leu Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 96
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 96
Asp Ile Val Met Thr Gln Ser His Leu Ser Met Ser Thr Ser Leu Gly
1 5 10 15
Asp Pro Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Val
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Arg Leu Ile
35 40 45
Tyr Ser Ala Ser Tyr Arg Tyr Ile Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ala Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala
65 70 75 80
Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Pro Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 97
<211> 119
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 97
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 Phe Asp Phe Ser Arg Tyr
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu
50 55 60
Lys Asp Lys Phe Ile 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser
115
<210> 98
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 98
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 99
<211> 122
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 99
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Asn Ser Phe
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Gly Gly 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 Phe Cys
85 90 95
Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 100
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 100
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
100 105
<210> 101
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 101
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Ala Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Trp Met Gln Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Tyr Pro Gly Asp Gly Asp Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Lys Thr Val Tyr
65 70 75 80
Met His Leu Ser Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Asp Tyr Tyr Gly Ser Asn Ser Leu Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser
115 120
<210> 102
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 102
Asp Ile Val Met Thr Gln Ser His Leu Ser Met Ser Thr Ser Leu Gly
1 5 10 15
Asp Pro Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Val
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Arg Leu Ile
35 40 45
Tyr Ser Ala Ser Tyr Arg Tyr Ile Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ala Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala
65 70 75 80
Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Pro Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105
<210> 103
<211> 120
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 103
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 Phe Ser Ser Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Ser Gly Asp Pro Ser Asn 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 Arg Asp Leu Pro Leu Val Tyr Thr Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 104
<211> 107
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 104
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Leu Arg His Tyr Tyr Val
20 25 30
Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Asp Ser Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Thr Tyr Thr Gly Gly Ala Ser Leu
85 90 95
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu
100 105
<210> 105
<211> 450
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 105
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 Phe Ser Ser Tyr
20 25 30
Tyr Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Gly Ile Ser Gly Asp Pro Ser Asn 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 Arg Asp Leu Pro Leu Val Tyr Thr Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 106
<211> 213
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 106
Asp Ile Glu Leu Thr Gln Pro Pro Ser Val Ser Val Ala Pro Gly Gln
1 5 10 15
Thr Ala Arg Ile Ser Cys Ser Gly Asp Asn Leu Arg His Tyr Tyr Val
20 25 30
Tyr Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Val Leu Val Ile Tyr
35 40 45
Gly Asp Ser Lys Arg Pro Ser Gly Ile Pro Glu Arg Phe Ser Gly Ser
50 55 60
Asn Ser Gly Asn Thr Ala Thr Leu Thr Ile Ser Gly Thr Gln Ala Glu
65 70 75 80
Asp Glu Ala Asp Tyr Tyr Cys Gln Thr Tyr Thr Gly Gly Ala Ser Leu
85 90 95
Val Phe Gly Gly Gly Thr Lys Leu Thr Val Leu Gly Gln Pro Lys Ala
100 105 110
Ala Pro Ser Val Thr Leu Phe Pro Pro Ser Ser Glu Glu Leu Gln Ala
115 120 125
Asn Lys Ala Thr Leu Val Cys Leu Ile Ser Asp Phe Tyr Pro Gly Ala
130 135 140
Val Thr Val Ala Trp Lys Ala Asp Ser Ser Pro Val Lys Ala Gly Val
145 150 155 160
Glu Thr Thr Thr Pro Ser Lys Gln Ser Asn Asn Lys Tyr Ala Ala Ser
165 170 175
Ser Tyr Leu Ser Leu Thr Pro Glu Gln Trp Lys Ser His Arg Ser Tyr
180 185 190
Ser Cys Gln Val Thr His Glu Gly Ser Thr Val Glu Lys Thr Val Ala
195 200 205
Pro Thr Glu Cys Ser
210
<210> 107
<211> 449
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 107
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 Phe Asp Phe Ser Arg Tyr
20 25 30
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Ile
35 40 45
Gly Glu Ile Asn Pro Asp Ser Ser Thr Ile Asn Tyr Ala Pro Ser Leu
50 55 60
Lys Asp Lys Phe Ile 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 Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Asp Gly Asn Tyr Trp Tyr Phe Asp Val Trp Gly Gln Gly
100 105 110
Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe
115 120 125
Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu
130 135 140
Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp
145 150 155 160
Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu
165 170 175
Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser
180 185 190
Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro
195 200 205
Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp Lys
210 215 220
Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly Pro
225 230 235 240
Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser
245 250 255
Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp
260 265 270
Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn
275 280 285
Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val
290 295 300
Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu
305 310 315 320
Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys
325 330 335
Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr
340 345 350
Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu Thr
355 360 365
Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu
370 375 380
Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu
385 390 395 400
Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys
405 410 415
Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu
420 425 430
Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly
435 440 445
Lys
<210> 108
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 108
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Ile Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Val Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Asp Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Val Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 109
<211> 452
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 109
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Asn Ser Phe
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Gly Gly 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 Phe Cys
85 90 95
Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Lys
450
<210> 110
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 110
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Ser Asn Arg Ala Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Arg Ser Asn Trp Pro Pro
85 90 95
Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 111
<211> 450
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 111
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Ala Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Trp Met Gln Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Tyr Pro Gly Asp Gly Asp Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Lys Thr Val Tyr
65 70 75 80
Met His Leu Ser Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Asp Tyr Tyr Gly Ser Asn Ser Leu Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Lys
450
<210> 112
<211> 214
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 112
Asp Ile Val Met Thr Gln Ser His Leu Ser Met Ser Thr Ser Leu Gly
1 5 10 15
Asp Pro Val Ser Ile Thr Cys Lys Ala Ser Gln Asp Val Ser Thr Val
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ser Pro Arg Arg Leu Ile
35 40 45
Tyr Ser Ala Ser Tyr Arg Tyr Ile Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ala Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Val Gln Ala
65 70 75 80
Glu Asp Leu Ala Val Tyr Tyr Cys Gln Gln His Tyr Ser Pro Pro Tyr
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 113
<211> 727
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 113
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr
225 230 235 240
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg
260 265 270
Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
275 280 285
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly
450 455 460
Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro Leu Gly Val Arg Gly Gly
465 470 475 480
Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro
485 490 495
Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg
500 505 510
Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys
515 520 525
Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala
530 535 540
Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe
545 550 555 560
Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr
565 570 575
Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys
580 585 590
Val Glu Ile Lys Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
595 600 605
Gly Gly Ser Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys
610 615 620
Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe
625 630 635 640
Thr Ser Tyr Ser Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu
645 650 655
Glu Trp Met Gly Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala
660 665 670
Gln Lys Phe Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser
675 680 685
Thr Ala Tyr Leu Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val
690 695 700
Tyr Tyr Cys Ala Arg Asp Pro Ile Ala Ala Gly Tyr Trp Gly Gln Gly
705 710 715 720
Thr Leu Val Thr Val Ser Ser
725
<210> 114
<211> 723
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 114
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr
225 230 235 240
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg
260 265 270
Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
275 280 285
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly
450 455 460
Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly Ser Gly
465 470 475 480
Gly Gly Gly Ser Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
485 490 495
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
500 505 510
Val Ser Ser Thr Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
515 520 525
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
530 535 540
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
545 550 555 560
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr
565 570 575
Gly Ser Ser Pro Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys
580 585 590
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln
595 600 605
Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser
610 615 620
Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser
625 630 635 640
Ile Ser Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
645 650 655
Trp Ile Ser Val Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln
660 665 670
Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu
675 680 685
Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala
690 695 700
Arg Asp Pro Ile Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr
705 710 715 720
Val Ser Ser
<210> 115
<211> 632
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 115
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr
225 230 235 240
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg
260 265 270
Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
275 280 285
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly
450 455 460
Gly Gly Ser Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg
465 470 475 480
Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys
485 490 495
Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn
500 505 510
Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln
515 520 525
Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp
530 535 540
Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn
545 550 555 560
Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro
565 570 575
Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg
580 585 590
Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu
595 600 605
Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu
610 615 620
Gln Glu Ser Leu Arg Ser Lys Glu
625 630
<210> 116
<211> 642
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 116
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr
225 230 235 240
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg
260 265 270
Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
275 280 285
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly
450 455 460
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Asp Leu
465 470 475 480
Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala
485 490 495
Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp
500 505 510
Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu
515 520 525
Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe
530 535 540
Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys
545 550 555 560
Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val
565 570 575
Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser
580 585 590
Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys
595 600 605
Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala Glu Ile
610 615 620
Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser
625 630 635 640
Lys Glu
<210> 117
<211> 632
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 117
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr
225 230 235 240
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg
260 265 270
Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
275 280 285
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly
450 455 460
Gly Gly Ser Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg
465 470 475 480
Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys
485 490 495
Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn
500 505 510
Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln
515 520 525
Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp
530 535 540
Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn
545 550 555 560
Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro
565 570 575
Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg
580 585 590
Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu
595 600 605
Val Val Arg Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu
610 615 620
Gln Glu Ser Leu Arg Ser Lys Glu
625 630
<210> 118
<211> 642
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 118
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Lys Ala Glu Pro Lys Ser Cys Asp Lys Thr
225 230 235 240
His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly Gly Pro Ser
245 250 255
Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg
260 265 270
Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu Asp Pro
275 280 285
Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala
290 295 300
Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val
305 310 315 320
Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr
325 330 335
Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr
340 345 350
Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu
355 360 365
Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys
370 375 380
Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser
385 390 395 400
Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp
405 410 415
Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser
420 425 430
Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala
435 440 445
Leu His Asn Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Gly
450 455 460
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Asp Leu
465 470 475 480
Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala
485 490 495
Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp
500 505 510
Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu
515 520 525
Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe
530 535 540
Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys
545 550 555 560
Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val
565 570 575
Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser
580 585 590
Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys
595 600 605
Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala Glu Ile
610 615 620
Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser
625 630 635 640
Lys Glu
<210> 119
<211> 641
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 119
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
225 230 235 240
Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
340 345 350
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Cys
355 360 365
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
Arg Phe Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Ala Gly Gly Gly
450 455 460
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys Asp Leu Pro
465 470 475 480
Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln
485 490 495
Met Arg Lys Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe
500 505 510
Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr
515 520 525
Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser
530 535 540
Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe
545 550 555 560
Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile
565 570 575
Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile
580 585 590
Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu
595 600 605
Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala Glu Ile Met
610 615 620
Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys
625 630 635 640
Glu
<210> 120
<211> 236
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 120
Met Asp Met Arg Val Pro Ala Gln Leu Leu Gly Leu Leu Leu Leu Trp
1 5 10 15
Leu Pro Gly Ala Lys Cys Ala Ile Arg Met Thr Gln Ser Pro Ser Ser
20 25 30
Phe Ser Ala Ser Ala Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser
35 40 45
Glu Asn Ile Tyr Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys
50 55 60
Ser Pro Lys Leu Leu Ile Tyr Asn Ala Lys Thr Leu Ala Glu Gly Val
65 70 75 80
Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr
85 90 95
Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln His
100 105 110
His Tyr Ala Ile Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg Thr Val Ala Ala Pro Ser Val Phe Ile Phe Pro Pro Ser Asp
130 135 140
Glu Gln Leu Lys Ser Gly Thr Ala Ser Val Val Cys Leu Leu Asn Asn
145 150 155 160
Phe Tyr Pro Arg Glu Ala Lys Val Gln Trp Lys Val Asp Asn Ala Leu
165 170 175
Gln Ser Gly Asn Ser Gln Glu Ser Val Thr Glu Gln Asp Ser Lys Asp
180 185 190
Ser Thr Tyr Ser Leu Ser Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr
195 200 205
Glu Lys His Lys Val Tyr Ala Cys Glu Val Thr His Gln Gly Leu Ser
210 215 220
Ser Pro Val Thr Lys Ser Phe Asn Arg Gly Glu Cys
225 230 235
<210> 121
<211> 461
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 121
Met Gly Val Lys Val Leu Phe Ala Leu Ile Cys Ile Ala Val Ala Glu
1 5 10 15
Ala Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser
20 25 30
Glu Thr Leu Ser Ile Thr Cys Thr Val Ser Gly Val Ser Ile Ser Ser
35 40 45
Tyr Gly Leu His Trp Ile Arg Gln Pro Pro Gly Lys Ser Leu Glu Trp
50 55 60
Leu Gly Val Ile Trp Ala Ser Gly Arg Thr Asn Tyr Asn Pro Ala Leu
65 70 75 80
Lys Ser Arg Val Thr Ile Ser Gly Asp Thr Ser Lys Asn Gln Val Ser
85 90 95
Leu Lys Leu Ser Gly Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys
100 105 110
Ala Gly Ser Asn Trp Gly Tyr Ala Met Asp Tyr Trp Gly Gln Gly Thr
115 120 125
Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val Phe Pro
130 135 140
Leu Ala Pro Cys Ser Arg Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly
145 150 155 160
Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser Trp Asn
165 170 175
Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val Leu Gln
180 185 190
Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro Ser Ser
195 200 205
Ser Leu Gly Thr Lys Thr Tyr Thr Cys Asn Val Asp His Lys Pro Ser
210 215 220
Asn Thr Lys Val Asp Lys Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys
225 230 235 240
Pro Pro Cys Pro Ala Pro Glu Phe Leu Gly Gly Pro Ser Val Phe Leu
245 250 255
Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu
260 265 270
Val Thr Cys Val Val Val Asp Val Ser Gln Glu Asp Pro Glu Val Gln
275 280 285
Phe Asn Trp Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys
290 295 300
Pro Arg Glu Glu Gln Phe Asn Ser Thr Tyr Arg Val Val Ser Val Leu
305 310 315 320
Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys
325 330 335
Val Ser Asn Lys Gly Leu Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys
340 345 350
Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser
355 360 365
Gln Glu Glu Met Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys
370 375 380
Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln
385 390 395 400
Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly
405 410 415
Ser Phe Phe Leu Tyr Ser Arg Leu Thr Val Asp Lys Ser Arg Trp Gln
420 425 430
Glu Gly Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn
435 440 445
His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Leu Gly Lys
450 455 460
<210> 122
<211> 5
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 122
Gly Gly Gly Gly Ser
1 5
<210> 123
<211> 10
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 123
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10
<210> 124
<211> 15
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 124
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 125
<211> 22
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成肽
<400> 125
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Ala Gly Gly Gly Gly
1 5 10 15
Ser Gly Gly Gly Gly Ser
20
<210> 126
<211> 895
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 126
Glu Val Gln Leu Leu Glu Ser Gly Gly Gly Leu Val Gln Pro Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Val Ser Gly Phe Thr Phe Asn Ser Phe
20 25 30
Ala Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Gly Gly 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 Phe Cys
85 90 95
Ala Lys Asp Lys Ile Leu Trp Phe Gly Glu Pro Val Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro
115 120 125
Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr
130 135 140
Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr
145 150 155 160
Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro
165 170 175
Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr
180 185 190
Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn
195 200 205
His Lys Pro Ser Asn Thr Lys Val Asp Lys Arg Val Glu Pro Lys Ser
210 215 220
Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu
225 230 235 240
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
245 250 255
Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser
260 265 270
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
275 280 285
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
290 295 300
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
305 310 315 320
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro
325 330 335
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
340 345 350
Val Tyr Thr Leu Pro Pro Ser Arg Glu Glu Met Thr Lys Asn Gln Val
355 360 365
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
370 375 380
Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro
385 390 395 400
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
405 410 415
Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val
420 425 430
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
435 440 445
Ser Pro Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
450 455 460
Ser Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu
465 470 475 480
Met Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys
485 490 495
Asp Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe
500 505 510
Gln Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile
515 520 525
Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr
530 535 540
Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu
545 550 555 560
Glu Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met
565 570 575
Lys Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr
580 585 590
Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val
595 600 605
Arg Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu
610 615 620
Ser Leu Arg Ser Lys Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
625 630 635 640
Gly Pro Leu Gly Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
645 650 655
Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly
660 665 670
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr
675 680 685
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu
690 695 700
Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser
705 710 715 720
Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu
725 730 735
Pro Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro
740 745 750
Arg Thr Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly
755 760 765
Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val
770 775 780
Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser
785 790 795 800
Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val
805 810 815
Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val
820 825 830
Tyr Asn Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr
835 840 845
Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser
850 855 860
Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile
865 870 875 880
Ala Ala Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
885 890 895
<210> 127
<211> 893
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> 人工序列说明：合成多肽
<400> 127
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Ala Lys Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Trp Met Gln Trp Val Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Thr Ile Tyr Pro Gly Asp Gly Asp Thr Gly Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Lys Thr Val Tyr
65 70 75 80
Met His Leu Ser Ser Leu Ala Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Gly Asp Tyr Tyr Gly Ser Asn Ser Leu Asp Tyr Trp Gly Gln
100 105 110
Gly Thr Ser Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser Val
115 120 125
Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala Ala
130 135 140
Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val Ser
145 150 155 160
Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala Val
165 170 175
Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val Pro
180 185 190
Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His Lys
195 200 205
Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys Asp
210 215 220
Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly Gly
225 230 235 240
Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met Ile
245 250 255
Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His Glu
260 265 270
Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val His
275 280 285
Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr Arg
290 295 300
Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly Lys
305 310 315 320
Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile Glu
325 330 335
Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val Tyr
340 345 350
Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser Leu
355 360 365
Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu Trp
370 375 380
Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro Val
385 390 395 400
Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val Asp
405 410 415
Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met His
420 425 430
Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser Pro
435 440 445
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Cys
450 455 460
Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu
465 470 475 480
Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg
485 490 495
His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys
500 505 510
Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe Asn
515 520 525
Leu Phe Ser Thr Lys Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu
530 535 540
Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala
545 550 555 560
Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu
565 570 575
Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr
580 585 590
Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Ala
595 600 605
Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu
610 615 620
Arg Ser Lys Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Pro
625 630 635 640
Leu Gly Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Glu Ile
645 650 655
Val Leu Thr Gln Ser Pro Gly Thr Leu Ser Leu Ser Pro Gly Glu Arg
660 665 670
Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser Val Ser Ser Thr Tyr Leu
675 680 685
Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
690 695 700
Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro Asp Arg Phe Ser Gly Ser
705 710 715 720
Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Arg Leu Glu Pro Glu
725 730 735
Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Gly Ser Ser Pro Arg Thr
740 745 750
Phe Gly Gln Gly Thr Lys Val Glu Ile Lys Gly Gly Gly Gly Ser Gly
755 760 765
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gln Val Gln Leu Val Gln Ser
770 775 780
Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys
785 790 795 800
Ala Ser Gly Tyr Thr Phe Thr Ser Tyr Ser Ile Ser Trp Val Arg Gln
805 810 815
Ala Pro Gly Gln Gly Leu Glu Trp Met Gly Trp Ile Ser Val Tyr Asn
820 825 830
Gly Asn Thr Asn Tyr Ala Gln Lys Phe Gln Gly Arg Val Thr Met Thr
835 840 845
Thr Asp Thr Ser Thr Ser Thr Ala Tyr Leu Glu Leu Arg Ser Leu Arg
850 855 860
Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg Asp Pro Ile Ala Ala
865 870 875 880
Gly Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
885 890

Claims (43)

1.前药，包括人干扰素(IFN)激动剂多肽，掩蔽部分和载体部分，其中，
所述掩蔽部分包括抗体的抗原结合片段，其可以和人干扰素激动剂多肽结合并抑制所述人干扰素激动剂多肽的生物学活性，
所述人干扰素激动剂多肽为干扰素α(IFNα)且与所述载体部分融合，以及，
所述掩蔽部分可选择地通过肽连接物与所述人干扰素激动剂多肽或所述载体部分融合。
2.前药，包括人干扰素(IFN)激动剂多肽，掩蔽部分和载体部分，其中，
所述掩蔽部分与人干扰素激动剂多肽结合并抑制所述人干扰素激动剂多肽的生物学活性，
所述人干扰素激动剂多肽与所述载体部分融合，且
所述掩蔽部分可选择地通过肽连接物与所述人干扰素激动剂多肽或所述载体部分融合。
3.根据权利要求1所述的前药，其特征在于，所述IFNα为IFNα-2a，IFNα-2b，或其类似物。
4.根据权利要求2所述的前药，其特征在于，所述IFN为IFNα-2a，IFNα-2b，IFNγ，或其类似物。
5.根据权利要求4所述的前药，其特征在于，所述IFNγ包括选自SEQ ID NO:5,6和7或与SEQ ID NO:5,6或7具有至少90％同源性的氨基酸序列。
6.根据权利要求1-4任一项所述的前药，其特征在于，所述IFNα-2a包括选自SEQ IDNO:65或与SEQ ID NO:65具有至少95％同源性的氨基酸序列。
7.根据权利要求1-4任一项所述的前药，其特征在于，所述IFNα-2b包括选自SEQ IDNO:66或与SEQ ID NO:66具有至少95％同源性的氨基酸序列。
8.根据权利要求1-7任一项所述的前药，其特征在于，所述IFN激动剂多肽通过不可切割肽连接物与所述载体融合，且所述掩蔽部分通过可切割肽连接物或不可切割肽连接物与所述载体融合。
9.根据权利要求1-7任一项所述的前药，其特征在于，所述IFN激动剂多肽通过不可切割肽连接物或可切割连接物与所述载体融合，且所述掩蔽部分通过不可切割肽连接物与所述载体融合。
10.根据权利要求1-7任一项所述的前药，其特征在于，所述载体包括抗体Fc结构域，所述Fc结构域的第一Fc多肽链包含knob突变，第二Fc多肽链包含hole突变；其中，所述IFN激动剂多肽通过可切割肽连接物与所述第一Fc多肽链融合，所述掩蔽部分通过不可切割肽连接物与所述第二Fc多肽链融合。
11.根据权利要求1-7任一项所述的权利要求，其特征在于，所述载体部分为抗体Fc结构域或为包含knobs-into-holes突变的抗体，其中所述人IFN激动剂多肽和其掩蔽部分分别与抗体Fc结构域的不同多肽链或与抗体不同重链融合。
12.根据权利要求1-7所述的前药，其特征在于，所述载体为抗体，所述前药包括两条通过不可切割肽连接物分别与抗体两条重链的C末端融合的IFN激动剂多肽，以及两个通过可切割肽连接物分别与两条IFN激动剂多肽融合的掩蔽部分。
13.根据权利要求1-11任一项所述的前药，其特征在于，所述肽连接物为可切割肽连接物，所述肽连接物包括以下物质的底物序列：尿激酶型纤溶酶原激活剂(uPA)、膜型基质金属蛋白酶(MT1-MMP)、基质金属蛋白酶2(MMP2)、MMP9、蛋白裂解酶、豆荚蛋白、纤溶酶、TMPRSS-3/4、组织蛋白酶,胱天蛋白酶,人嗜中性粒细胞弹性蛋白酶,β-分泌酶,或PSA，或(i)uPA和MMP2二者，(ii)uPA和MMP9二者，或(iii)蛋白裂解酶,MMP2以及MMP9。
14.根据权利要求8-13任一项所述的前药，其特征在于，所述可切割肽连接物包括选自SEQ ID NOs:26-45的氨基酸序列。
15.根据权利要求8-13任一项所述的前药，其特征在于，所述不可切割肽连接物包括选自SEQ ID NOs:122-125的氨基酸序列。
16.根据权利要求8-13任一项所述的前药，其特征在于，所述可切割肽连接物可被位于肿瘤位点或其周围微环境中的一个或多个蛋白酶切割，且所述切割使所述前药在肿瘤位点或其周围微环境中活化。
17.根据前述任一项权利要求所述的前药，其特征在于，所述掩蔽部分抑制所述IFN激动剂多肽和IFN受体的结合。
18.根据前述任一项权利要求所述的前药，其特征在于，所述掩蔽部分包括单链抗体(scFv)，所述单链抗体包括具有如SEQ ID NO:1所示氨基酸序列的重链可变区和具有如SEQID NO:2所示氨基酸序列的轻链可变区，或具有如SEQ ID NO:3所示氨基酸序列的重链可变区和如SEQ ID NO:4所示氨基酸序列的轻链可变区。
19.根据权利要求2或4-18任一项所述的前药，其特征在于，所述掩蔽部分选自干扰素γ受体1胞外结构域(IFNGR1-ECD)或其功能类似物，或可结合IFNγ的抗体或其结合片段。
20.根据权利要求19所述的前药，其特征在于，所述掩蔽部分包括IFNGR1-ECD或其功能类似物，并且所述IFNGR1-ECD可选择地包括选自SEQ ID NOs:8和9的氨基酸序列。
21.根据前述任一项权利要求所述的前药，其特征在于，所述载体部分为抗体Fc结构域，抗体，或抗体的抗原结合片段。
22.根据前述任一项权利要求所述的前药，其特征在于，所述载体部分包括抗体或其抗原结合片段，所述抗体或其抗原结合片段与肿瘤细胞，肿瘤微环境中的细胞，癌细胞或免疫细胞表面表达的抗原结合。
23.根据权利要求21所述的前药，其特征在于，所述免疫细胞选自NK细胞，T细胞，B细胞和巨噬细胞。
24.根据权利要求21-23任一项所述的前药，其特征在于，所述载体部分包括的抗体或其抗原结合片段可与如下述抗原结合：PD-1、LAG-3、TIGIT、SIRPα、ILT2、CD206、NKD2G、CTLA-4、CD8、NKG2A、CD16a、CD38、BCMA、细胞表面糖蛋白CD2亚型1(CS1)、PD-L1、CD47、CMET、EGFR、ROR1、TROP-2、HER2、CLDN18.2和VEGFR2。
25.根据权利要求21-23任一项所述的前药，其特征在于，所述载体部分包括可与PD-1结合的抗体或其抗原结合片段，其中，所述抗体的轻链可变区含有SEQ ID NO:10氨基酸序列，重链可变区含有SEQ ID NO:11氨基酸序列；或轻链可变区含有SEQ ID
NO:12氨基酸序列，重链可变区含有SEQ ID NO:13氨基酸序列。
26.根据权利要求21-23任一项所述的前药，其特征在于，所述载体部分包括抗体或抗原结合片段，包括：
i)具有SEQ ID NO:97或与SEQ ID NO:97具有至少95％同源性氨基酸序列的重链可变区，以及具有SEQ ID NO:98或与SEQ ID NO:98具有至少95％同源性氨基酸序列的轻链；或
ii)具有SEQ ID NO:99或与SEQ ID NO:99具有至少95％同源性氨基酸序列的重链可变区，以及具有SEQ ID NO:100或与SEQ ID NO:100具有至少95％同源性氨基酸序列的轻链；或
iii)具有SEQ ID NO:101或与SEQ ID NO:101具有至少95％同源性氨基酸序列的重链可变区，以及具有SEQ ID NO:102或与SEQ ID NO:102具有至少95％同源性氨基酸序列的轻链。
27.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括第一多肽链和第二多肽链，其中，所述第一多肽链包括选自SEQ ID NOs:67,68,69和70，或与SEQ ID NO:67,68,69或70具有至少95％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NOs:71和72，或与SEQ ID NO:71或72具有至少95％同源性的氨基酸序列。
28.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括第一多肽链和第二多肽链，其中，所述第一多肽链包括选自SEQ ID NOs:73,74,75和76，或与SEQ ID NO:73,74,75或76具有至少95％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NO:77,78，或与SEQ ID NO:77或78具有至少95％同源性的氨基酸序列。
29.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括具有SEQ IDNO:46或与SEQ ID NO:46具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:79,80,81和82，或与SEQ ID NO:79,80,81或82具有至少98％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NOs:83和84，或与SEQ ID NO:83或84具有至少98％同源性的氨基酸序列。
30.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链包括具有SEQ IDNO:53或与SEQ ID NO:53具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:85,86,87和88，或与SEQ ID NO:85,86,87或88具有至少98％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NOs:89和90，或与SEQ ID NO:89或90具有至少98％同源性的氨基酸序列。
31.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括两条相同的轻链，第一重链多肽链和第二重链多肽链，其中，所述轻链具有SEQ ID NO:120或与SEQ ID NO:120具有至少95％同源性的氨基酸序列，所述第一重链多肽链包括选自SEQ ID NOs:113和114，或与SEQ ID NO:113或114具有至少98％同源性的氨基酸序列，以及所述第二多肽链包括选自SEQ ID NOs:115,116,117,118和119，或与SEQ ID NO:115,116,117,118或119具有至少98％同源性的氨基酸序列。
32.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括两条相同的轻链，两条相同的重链多肽链；其中，所述轻链具有SEQ ID NO:94或与SEQID NO:94具有至少95％同源性的氨基酸序列，所述重链多肽链具有SEQ ID NO:126或与SEQID NO:126具有至少98％同源性的氨基酸序列。
33.根据权利要求1-4,6-11,13-17或21-23任一项所述的前药，其特征在于，所述前药包括两条相同的轻链，两条相同的重链多肽链；其中，所述轻链具有SEQ ID NO:96或与SEQID NO:96具有至少95％同源性的氨基酸序列，所述重链多肽链具有SEQ ID NO:127或与SEQID NO:127具有至少98％同源性的氨基酸序列。
34.包括根据权利要求1-33任一项所述前药和药学上可接受的赋形剂的药物组合物。
35.编码根据权利要求1-33任一项所述前药的多核苷酸。
36.包括根据权利要求35所述多核苷酸的表达载体。
37.包括根据权利要求36所述表达载体的宿主细胞。
38.根据权利要求37所述的宿主细胞，其特征在于，所述宿主细胞中编码蛋白裂解酶(matriptase)、uPA、MMP-2和/或MMP-9的基因被敲除。
39.制备根据权利要求1-33任一项所述前药的方法，包括：
在允许所述前药表达的条件下培养根据权利要求37或38所述的宿主细胞，所述宿主细胞为哺乳动物细胞，
分离所述前药。
40.对有需要的患者治疗癌症、感染性疾病或刺激其免疫系统的方法，包括向患者施用治疗有效剂量的根据权利要求34所述的药物组合物。
41.根据权利要求1-33任一项所述的前药在对有需要的患者治疗癌症、感染性疾病或刺激其免疫系统中的应用。
42.根据权利要求1-33任一项所述前药在制备对有需要的患者治疗癌症或感染性疾病或刺激其免疫系统的药物中的应用。
43.根据权利要求40所述的方法，权利要求41所述前药的应用，或根据权利要求42所述的应用，其中，所述患者患有病毒性感染，或选自由以下的癌症组成的组中的一种：乳腺癌、肺癌、胰腺癌、食管癌、甲状腺髓样癌、卵巢癌、子宫癌、前列腺癌、睾丸癌、结肠癌和胃癌。
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