CN109475622A - 使用il-33抑制剂抑制过敏反应 - Google Patents

使用il-33抑制剂抑制过敏反应 Download PDF

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CN109475622A
CN109475622A CN201780014394.8A CN201780014394A CN109475622A CN 109475622 A CN109475622 A CN 109475622A CN 201780014394 A CN201780014394 A CN 201780014394A CN 109475622 A CN109475622 A CN 109475622A
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M·隆代伊
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Abstract

一种抑制或预防哺乳动物中的过敏反应，特别是针对食物抗原的过敏反应的方法，其包括向所述哺乳动物施用IL‑33抑制剂。

Description

使用IL-33抑制剂抑制过敏反应
优先权信息
本申请要求于2016年1月14日提交的美国临时申请号62/278,671的权益。该临时申请的公开内容出于所有目的以其整体并入本文。
通过引用并入的以电子形式提交的材料
通过引用整体并入本文的是与本文同时提交并且如下标识的计算机可读核苷酸/氨基酸序列表：2017年1月13日创建的名为“727217_ST25.txt”的一个283,263字节的ASCII(文本)文件。
发明背景
相当大比例的个体患有食物过敏，这代表了日益增加的社会经济负担。许多食物抗原可引发过敏反应，在最严重的情况下，其可能导致过敏性休克和死亡。食物过敏最常见的原因是花生过敏，其在美国折磨多达10％的儿童和1％的成人。一旦发生过敏反应，患者可能表现出一系列症状，并且在极端情况下，他们必须住院并迅速治疗。
对于所有特应性疾病，已经在花生过敏患者中描述了高水平的免疫球蛋白E(IgE)和花生蛋白特异性IgE。目前的治疗涉及围绕避免食物中的花生的教育，但是鉴于花生被广泛并经常隐藏得用作食物成分，这可能是有问题的。此外，避免方法并不代表真正的“疗法”。
过敏反应存在于显著比例的花生过敏性个体中，并且在最严重的反应中，患者可能住院，并且如果不适当并快速治疗可能会死亡。在这些情况下，过敏反应的迅速识别和治疗必须在它们出现时尽快进行。过敏反应的唯一有效治疗是肌内施用肾上腺素(EpiPen)，而氧气、雾化沙丁胺醇、系统性皮质类固醇和组胺H1和/或H2受体拮抗剂可以帮助缓解继发症状。
目前正在探索主要基于抗原特异性(即，花生)脱敏的免疫治疗方法，以寻找对于这种危及生命的过敏症的有效治疗。其他策略是基于抗原脱敏，由此在用触发过敏原/抗原进行的慢性和长期攻击后致病性抗原特异性T细胞受到再训练。临床研究提供了对致病性T细胞潜在影响的有趣证据，这具有一些临床益处。然而，脱敏治疗方法具有引起过敏性休克反应的内在风险，因此这类方法可能限于对脱敏治疗的过敏反应风险较低的较轻微患者。此外，具有食物过敏的患者通常对不只对一种食物抗原过敏，并且还患有其他特应性疾病。按照定义，这些脱敏方法对于单一抗原是特异性的，并且不直接针对过敏性休克反应的原因，并且在某些情况下可能实际上诱导该反应。
因此，仍然需要用于抑制或预防过敏反应的新方法。
发明概述
本发明提供了用于抑制或预防哺乳动物中的过敏反应的方法，其包括向所述哺乳动物施用IL-33抑制剂。还提供了相关的方法和组合物。
发明详述
本发明提供了用于抑制或预防哺乳动物中的过敏反应(特别是对食物抗原的过敏反应(即，食物过敏))的方法，其包括向哺乳动物施用IL-33抑制剂。如本文所用，术语“食物过敏”是指在哺乳动物中响应于摄入的物质或“食物抗原”(例如，坚果、花生、贝类、鱼、奶、蛋、小麦和大豆)所引发的慢性或急性免疫超敏反应(例如，I型超敏反应)。在这个意义上，“食物抗原”与“食物过敏原”同义使用。食物过敏的鉴定和诊断在本领域普通技术人员中是常规的。食物过敏反应的临床表现包括但不限于皮疹、湿疹、特应性皮炎、麻疹、荨麻疹、血管性水肿、哮喘、鼻炎、气喘、打喷嚏、呼吸困难、呼吸道肿胀、呼吸急促、其他呼吸道症状、腹痛、痉挛、恶心、呕吐、腹泻、黑便、心动过速、低血压、晕厥、癫痫发作和过敏性休克。诊断食物过敏的方法包括，例如，消除饮食、用疑似过敏原进行口服食物攻击、皮肤点刺试验、在受试者血液内检测过敏原特异性免疫球蛋白(例如，IgE)、以及分子过敏成分测试。可以通过相比于阴性对照中的水平(例如，已知处于非过敏状态的相同类型的正常、非患病受试者或与特定过敏原接触之前的给定个体的血清水平)增加的血清IgE水平或增加的IL-9表达和分泌，和/或过敏性休克的临床表现来定义过敏反应。
不希望受任何特定理论或作用机制的束缚，据信过敏反应(特别是对食物过敏原的过敏反应)涉及IL-33或IL-33活性的增加，其引起或恶化过敏反应。因此，用IL-33抑制剂治疗可减少或消除过敏反应或其症状。
进一步认为，在至少一些实施方式中，本文提供的方法可以靶向致病级联的不同关键步骤，其控制花生过敏反应从开始、过敏原特异性致病性T细胞的功能到过敏性表现的控制。IL-33是预先形成的细胞因子，其主要存在于具有屏障功能的细胞中，例如内皮细胞和上皮细胞。其在过敏原、病原体或环境因子攻击后迅速释放，从而充当Th2炎症反应的主要和初始触发物。经由IL-33对肥大细胞和嗜碱细胞的直接活性影响致病性Th2T细胞，从而放大过敏反应，进而IL-33多效性功能扩展至免疫反应的调控。因此，据信IL-33抑制在不同阶段控制致病性花生(食物)过敏反应。IL-33抑制也可以使伴随食物过敏(即坚果)，或具有花生(食物)过敏患者中经常存在的其他特应性疾病(如特应性皮炎或哮喘)的花生过敏患者受益。因此，IL-33抑制将代表一种用于共享这种致病级联的疾病的整体治疗方法，进一步帮助花生(食物)过敏患者。
本文提供的方法可用于治疗任何哺乳动物，尤其是人。据信该方法对具有增加IL-33表达或信号传导的基因突变的哺乳动物或人类特别有效，特别是在暴露于抗原(例如，食物抗原)之后。
IL-33(也称为在高内皮小静脉中的核因子(NF)(NF-HEV))是IL-1家族的细胞因子，该家族还包括炎性细胞因子IL-1α、IL-1β和IL-18。已经显示IL-33通过ST2受体和IL1RAP受体发出信号。IL-33广泛表达于各种组织(包括胃、肺、脊髓、脑和皮肤)以及细胞(包括支气管和小气道内层平滑肌细胞和上皮细胞)。IL-33表达由肺和真皮成纤维细胞中的IL-1β和肿瘤坏死因子-α(TNF-α)诱导，并且在较小程度上由巨噬细胞活化诱导。已显示IL-33处理在小鼠中诱导T辅助细胞(Th)2型应答，如Th2细胞因子产生和血清免疫球蛋白的增加所示。用IL-33系统性处理小鼠导致肺和消化道中的病理学变化(参见，例如，Choi等，Blood，114(14)：3117-3126(2009)；和Yagami等，J.Immunology，185(10)：5743-5750(2010))。
IL-33以30kDa前体蛋白形式产生，其在体外被胱天蛋白酶-1裂解，释放成熟的18-kDa形式(参见，例如，Schmitz等，Immunity，23(5)：479-490(2005))。在与ST2受体结合后，IL-33促进核因子(NF)-κB和丝裂原活化蛋白激酶(MAPK)的活化，从而导致Th2细胞因子的转录增加(Schmitz等，同上)。
可以根据本发明使用任何IL-33抑制剂。IL-33抑制剂可以是抑制IL-33蛋白表达的分子(例如，反义或siRNA)。或者，IL-33抑制剂可以是阻断IL-33与受体ST2和IL1RAP结合的分子。例如，IL-33抑制剂可以是分离或纯化的IL-33表位，其以间接或变构方式阻断IL-33与其受体的结合。IL-33抑制剂可以是IL-33结合剂，其可以是能够与IL-33结合或相互作用并影响其生物活性的任何物质。IL-33结合剂可以结合IL-33的表位，其阻断IL-33与受体ST2(也称为IL1RL1)和/或IL-1受体辅助蛋白(IL1RAP)的结合并抑制IL-33介导的信号传导。例如，IL-33结合剂可包含IL-33受体或其片段。在一个实施方式中，IL-33结合剂包含ST2的IL-33结合结构域。在另一个实施方式中，ST2的IL-33结合结构域与异源多肽融合，例如免疫球蛋白的Fc部分。IL-33结合剂还可以是免疫球蛋白或其抗体抗原结合抗体片段，其实例在本文中进行描述。IL-33表达或活性的其他抑制剂可包括例如阻断ST2、IL-1RAP的抗体、丙烯醛、青蒿琥酯、牡荆素，I-茶氨酸或长春西汀。
如本文所用的术语“免疫球蛋白”或“抗体”是指在脊椎动物血液或其他体液中发现的蛋白，其被免疫系统用于识别和中和外源性物质，例如细菌和病毒。因为从其天然环境中移除，所以所述多肽是“分离的”。在一个优选实施方式中，免疫球蛋白或抗体是包含至少一个互补决定区(CDR)的蛋白。CDR形成抗体的“高变区”，其负责与抗原结合(下面进一步讨论)。完整的免疫球蛋白通常由四个多肽组成：两个相同拷贝的重(H)链多肽和两个相同拷贝的轻(L)链多肽。各重链均含有一个N端可变(VH)区和三个C端恒定(CH1、CH2和CH3)区，并且各轻链均含有一个N端可变(VL)区和一个C端恒定(CL)区。基于其恒定结构域的氨基酸序列，可以将抗体的轻链分成两种不同类型之一，即kappa(κ)或Iambda(λ)。在典型的免疫球蛋白中，各轻链与重链通过二硫键连接，并且两条重链之间彼此通过二硫键相互连接。轻链可变区与重链可变区对齐，轻链恒定区与重链第一恒定区对齐。重链的其余恒定区彼此相互对齐。
各对轻链和重链的可变区形成抗体的抗原结合位点。VH和VL区具有相同的基本结构，各区域均包含四个框架(FW或FR)区。如本文所用的术语“框架区”是指在可变区内位于高变或互补决定区(CDR)之间的相对保守的氨基酸序列。每个可变区中具有四个框架区，被命名为FR1、FR2、FR3和FR4。框架区形成提供可变区结构框架的β片层(参见例如，C.A.Janeway等(编)，Immunobiology，第5版，Garland Publishing，New York，NY(2001))。
框架区通过三个互补决定区(CDR)相连。如上所述，三个CDR(称为CDR1、CDR2和CDR3)形成抗体的“高变区”，其负责与抗原结合。CDR形成环状连接，并在某些情况下包括部分由框架区形成的β片层结构。虽然轻链和重链的恒定区并不直接参与抗体与抗原的结合，但是恒定区会影响可变区的定向。恒定区还表现出不同的效应器功能，如通过与效应器分子和细胞的相互作用来参与抗体依赖性补体介导溶解或抗体依赖性细胞毒作用。
与IL-33结合的抗体及其组分是本领域已知的(参见，例如，US 2014/0271658、US2009/0041718 A1、2012/0263709 A1、WO2015099175；WO 2016077381；和WO 2016/077366)。抗IL-33抗体也可从诸如Abcam(Cambridge，MA)等来源商购获得。ST2或ST2L的抗体公开于例如US 2014/0004107和US 9090694中。
抗IL-33抗体可以包含免疫球蛋白重链多肽，其包含SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中任一的氨基酸序列，或与SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ IDNO：206-217中的任一具有至少90％同一性的氨基酸序列。在本发明的一个实施方式中，分离的免疫球蛋白重链多肽包含如下氨基酸序列、由如下氨基酸序列组成为或基本由如下氨基酸序列组成：SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQ IDNO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中任一的氨基酸序列。当免疫球蛋白重链多肽基本上由SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中任一的氨基酸序列组成时，多肽中可包含不会实质上影响该多肽的其他组分(例如，促进纯化或分离的蛋白质部分，如生物素)。当免疫球蛋白重链多肽由SEQ ID NO：1，SEQ ID NO：2、SEQID NO：5-50、SEQ ID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中任一的氨基酸序列组成时，该多肽不包含任何其他组分(即，对本发明的免疫球蛋白重链多肽而言非内源性的组分)。
免疫球蛋白重链多肽可包含与SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188或SEQ ID NO：206-217中的任一具有至少90％同一性(例如，至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％或100％同一性)的氨基酸序列。如本文所述的核酸或氨基酸序列“同一性”可通过将目标核酸或氨基酸序列与参考核酸或氨基酸序列进行比对来测定。同一性百分数是目标序列和参考序列间相同(即，具有同一性)的核苷酸或氨基酸残基数目除以最长序列长度(即，目标序列或参考序列中长度更长的那个)。用于获得优化比对以及计算两个或多个序列间同一性的多种数学算法是已知的，并被引入多种可用软件程序。此类程序的实例包括CLUSTAL-W、T-Coffee和ALIGN(用于比对核酸和氨基酸序列)、BLAST程序(例如，BLAST 2.1、BL2SEQ及其后来版本)和FASTA程序(例如，FASTA3x、FASTM和SSEARCH)(用于序列比对和序列相似性搜索)。序列比对算法还公开在例如Altschul等，J.Molecular Biol.，215(3):403-410(1990)，Beigert等，Proc.Natl.Acad.Sci.USA，106(10):3770-3775(2009)，Durbin等编，Biological SequenceAnalysis:Probabilistic Models of Proteins and Nucleic Acids，CambridgeUniversity Press，Cambridge，UK(2009)，Soding，Bioinformatics，21(7):951-960(2005)，Altschul等，Nucleic Acids Res.，25(17):3389-3402(1997)，和Gusfield，Algorithms on Strings,Trees and Sequences，Cambridge University Press，Cambridge UK(1997)中。
抗IL-33抗体可以包含免疫球蛋白轻链多肽，其包含SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ ID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中任一的氨基酸序列，或与SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ ID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中的任一具有至少90％同一性的氨基酸序列。在本发明的一个实施方式中，分离的免疫球蛋白轻链多肽包含如下氨基酸序列、由如下氨基酸序列组成为或基本由如下氨基酸序列组成：SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ ID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中任一的氨基酸序列。当免疫球蛋白轻链多肽基本上由SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ IDNO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中任一的氨基酸序列组成时，多肽中可以包含不会实质上影响该多肽的其他组分(例如，促进纯化或分离的蛋白质部分，如生物素)。当免疫球蛋白轻链多肽由SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ IDNO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中任一的氨基酸序列组成时，该多肽不包含任何其他组分(即，对免疫球蛋白轻链多肽而言非内源性的组分)。
免疫球蛋白轻链多肽可包含与SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQID NO：141-175、SEQ ID NO：189-205或SEQ ID NO：218-231中的任一具有至少90％同一性(例如，至少91％、至少92％、至少93％、至少94％、至少95％、至少96％、至少97％、至少98％、至少99％或100％同一性)的氨基酸序列。如本文所述的核酸或氨基酸序列“同一性”可使用本文所述的方法测定。
前述免疫球蛋白重链多肽和/或轻链多肽的一个或多个氨基酸可被不同氨基酸替换或取代。氨基酸“替换”或“取代”是指在多肽序列内给定位置或残基处的一个氨基酸被另一氨基酸在相同位置或残基处替换。
氨基酸可被大致归类为“芳香族”或“脂肪族”。芳香族氨基酸包含芳环。“芳香族”氨基酸的实例包括组氨酸(H或His)、苯丙氨酸(F或Phe)、酪氨酸(Y或Tyr)和色氨酸(W或Trp)。非芳香族氨基酸可被大致归类为“脂肪族”。“脂肪族”氨基酸的实例包括甘氨酸(G或Gly)、丙氨酸(A或Ala)、缬氨酸(V或Val)、亮氨酸(L或Leu)、异亮氨酸(I或lie)、甲硫氨酸(M或Met)、丝氨酸(S或Ser)、苏氨酸(T或Thr)、半胱氨酸(C或Cys)、脯氨酸(P或pro)、谷氨酸(E或Glu)、天冬氨酸(A或Asp)、天冬酰胺(N或Asn)、谷氨酰胺(Q或Gln)、赖氨酸(K或Lys)和精氨酸(R或Arg)。
可以将脂肪族氨基酸再分成四个亚组。“大脂肪族非极性亚组”由缬氨酸、亮氨酸和异亮氨酸组成。“脂肪族微极性亚组”由甲硫氨酸、丝氨酸、苏氨酸和半胱氨酸组成。“脂肪族极性/带电荷亚组”由谷氨酸、天冬氨酸、天冬酰胺、谷氨酰胺、赖氨酸和精氨酸组成。“小残基亚组”由甘氨酸和丙氨酸组成。可以将带电荷/极性氨基酸组再细分成三个亚组：“正电荷亚组”由赖氨酸和精氨酸组成，“负电荷亚组”由谷氨酸和天冬氨酸组成，且“极性亚组”由天冬酰胺和谷氨酰胺组成。
可以将芳香族氨基酸再分成两亚组：“氮环亚组”由组氨酸和色氨酸组成且“苯基亚组”由苯丙氨酸和酪氨酸组成。
氨基酸替换或取代可以是保守性的、半保守性的或非保守性的。短语“保守性氨基酸取代”或“保守性突变”是指一个氨基酸被与其具有共同性质的另一个氨基酸取代。确定各氨基酸之间共同性质的有效方法是分析同源有机体相应蛋白间氨基酸变化的归一化频率(Schulz和Schirmer，Principles of Protein Structure，Springer-Verlag，New York(1979))。根据此类分析，可以将氨基酸的组定义为组内的氨基酸可以优选地彼此互换，并且其对总体蛋白结构的影响彼此最为类似(Schulz和Schirmer，同上)。
保守性氨基酸取代的实例包括上述亚组内部的氨基酸取代，例如赖氨酸取代精氨酸，反之亦然，这样可以保持其带有正电荷；谷氨酸取代天冬氨酸，反之亦然，这样可以保持其带有负电荷；丝氨酸取代苏氨酸，这样能够保持其具有游离的-OH；以及谷氨酰胺取代天冬酰胺，这样能够保持其具有游离的-NH2。
“半保守性突变”包括用属于上文所列同一组但不属于同一亚组的氨基酸进行的氨基酸取代。例如，天冬氨酸取代天冬酰胺，或天冬酰胺取代赖氨酸，这均涉及属于同一组但是不同亚组的氨基酸。“非保守性突变”涉及不同组之间的氨基酸取代，例如赖氨酸取代色氨酸，或苯丙氨酸取代丝氨酸等。
此外，可将一个或多个氨基酸插入前述免疫球蛋白重链多肽和/或轻链多肽。可以将任意数量的任何适当氨基酸插入免疫球蛋白重链多肽和/或轻链多肽的氨基酸序列。在此方面，可以将至少一个氨基酸(例如，2个或更多、5个或更多、或者10个或更多的氨基酸)，但不超过20个氨基酸(例如，18个或更少、15个或更少或者12个或更少的氨基酸)插入免疫球蛋白重链多肽和/或轻链多肽的氨基酸序列。优选地，将1-10个氨基酸(例如，1、2、3、4、5、6、7、8、9或10个氨基酸)插入免疫球蛋白重链多肽和/或轻链多肽的氨基酸序列。在此方面，可以在任意适当位置将氨基酸插入任一前述免疫球蛋白重链多肽和/或轻链多肽。优选地，将氨基酸插入免疫球蛋白重链多肽和/或轻链多肽的CDR(例如，CDR1、CDR2或CDR3)。
分离的免疫球蛋白重链多肽和轻链多肽不限于包含本文所述特定氨基酸序列的多肽。事实上，免疫球蛋白重链多肽或轻链多肽可为与上述免疫球蛋白重链多肽或轻链多肽竞争结合IL-33的任何重链多肽或轻链多肽。在此方面，例如，免疫球蛋白重链多肽或轻链多肽可为结合至被本文所述重链和轻链多肽所识别的相同IL-33表位的任何重链多肽或轻链多肽。抗体竞争可使用采用ELISA、免疫印迹或免疫组织化学方法的常规肽竞争测定法(参见例如，美国专利4,828,981和8,568,992；以及Braitbard等，Proteome Sci.，4:12(2006))来测定。
免疫球蛋白重链多肽和/或免疫球蛋白轻链多肽的任意氨基酸残基均可以被不同氨基酸残基以任意组合取代，或者可以被删除或插入，只要氨基酸取代、插入和/或删除的结果是使得IL-33结合剂的生物活性增强或改善即可。IL-33结合剂的“生物活性”是指，例如，与特定IL-33表位的结合亲和性、对IL-33结合其受体的中和或抑制、在体内对IL-33活性的中和或抑制(例如，IC50)、药代动力学性质以及交叉反应性(例如，与IL-33蛋白的非人同源或直系同源，或与其他蛋白或组织的交叉反应性)。本领域已知的抗原结合剂的其他生物学性质或特性包括例如亲和力、选择性、溶解性、折叠、免疫毒性、表达和制剂。可以采用标准技术对上述性质或特性进行观察、测量和/或评估，所述标准技术包括但不限于，ELISA、竞争性ELISA、表面等离子体共振分析(BIACORETM)或KINEXATM、体外或体内中和试验、受体-配体结合试验、细胞因子或生长因子产生和/或分泌检测、以及信号转导和免疫组化试验。
IL-33结合剂优选抑制或中和至少约20％、约30％、约40％、约50％、约60％、约70％、约80％、约90％、约95％、约100％，或前述值中任意两个所定义的范围的IL-33活性。如本文所用的针对IL-33结合剂活性的术语“抑制”或“中和”是指基本上拮抗、抑制、阻止、限制、延缓、破坏、改变、消除、终止或逆转例如IL-33的生物活性或与IL-33相关的疾病或病症的进程或严重度的能力。
IL-33结合剂可以是蛋白质(例如，抗体或抗体片段)，其包含一种或多种免疫球蛋白重链多肽和/或一种或多种免疫球蛋白轻链多肽，或者基本由其组成或者由其组成。
如本文所述的IL-33结合剂可以是完整抗体，或者抗体片段。术语“抗体的片段”、“抗体片段”和“抗体的功能性片段”在本文中可以互换使用，其是指保留与抗原特异性结合能力的抗体的一个或多个片段(参见，通常，Hol Iiger等，Nat.Biotech.，23(9):1126-1129(2005))。分离的IL-33结合剂可以含有任意IL-33结合抗体片段。抗体片段优选包含例如一个或多个CDR、可变区(或其部分)、恒定区(或其部分)、或其组合。抗体片段的实例包括但不限于，(i)Fab片段，其是由VL、VH、CL和CH1结构域组成的单价片段，(ii)F(ab’)2片段，其是包含在铰链区通过二硫键连接的两个Fab片段的二价片段，(iii)Fv片段，其由抗体单臂的VL和VH结构域组成，(iv)Fab’片段，其获自使用温和还原条件破坏F(ab’)2片段的二硫键，(V)二硫化物稳定化的Fv片段(dsFv)，和(vi)域抗体(dAb)，其为特异性结合抗原的抗体单一可变区结构域(VH或VL)多肽。
在IL-33结合剂包含免疫球蛋白重链或轻链多肽的片段的实施方式中，该片段可以为任意尺寸，只要该片段结合至IL-33，并优选地抑制IL-33的活性。在此方面，免疫球蛋白重链多肽的片段理想地包含约5和18个之间(例如，约5、6、7、8、9、10、11、12、13、14、15、16、17、18个，或前述值中任意两个所定义的范围)的氨基酸。类似地，免疫球蛋白轻链多肽的片段理想地包含约5和18个(例如，约5、6、7、8、9、10、11、12、13、14、15、16、17、18个，或前述值中任意两个所定义的范围)的氨基酸。
当IL-33结合剂是抗体或抗体片段时，抗体或抗体片段理想地包含任意合适类型的重链恒定区(Fc)。优选地，抗体或抗体片段包含基于野生型IgGl、IgG2或IgG4抗体的重链恒定区或其变体。
IL-33结合剂还可以是单链抗体片段。单链抗体片段的实例包括但不限于，(i)单链Fv(scFv)，其是由Fv片段的两个结构域(即，VL和VH)组成的单价分子，其由能够使两个结构域合成一条单一多肽链的合成连接子连接(参见，例如，Bird等，Science，242:423-426(1988)；Huston等，Proc.Natl.Acad.Sci.USA，85:5879-5883(1988)；和Osbourn等，Nat.Biotechnol.，16:778(1998))和(ii)双功能抗体(“diabody”)，其为多肽链的二聚体，其中各多肽链均包含通过肽连接子连接至VL的VH，所述肽连接子太短从而不允许在同一多肽链上的VH和VL之间配对，由此使不同VH-VL多肽链的互补结构域之间配对以产生具有两个功能性抗原结合位点的二聚体分子。抗体片段是本领域已知的，并且更加详细的描述在例如美国专利申请公开号2009/0093024 A1中。
IL-33结合剂还可以是胞内抗体或其片段。胞内抗体是一种在细胞内表达和发挥功能的抗体。胞内抗体通常缺少二硫键，并能够通过其特异性结合活性来调节靶基因的表达或活性。胞内抗体包括单结构域片段，例如分离的VH和VL结构域以及scFv。胞内抗体可以包括连接至胞内抗体N端或C端的亚细胞转运信号，以使其在靶蛋白所位于的亚细胞组件中高浓度表达。通过与靶基因的相互作用，胞内抗体通过例如加速靶蛋白降解和在非生理性亚细胞组件中隔离靶蛋白的机制，来调节靶蛋白的功能和/或实现表型/功能敲除。胞内抗体介导的基因失活的其他机制会依赖于胞内抗体导向的表位，如结合至靶蛋白上的催化位点，或结合至参与蛋白-蛋白、蛋白-DNA、或蛋白-RNA相互作用的表位。
IL-33结合剂还可以是抗体缀合物。在此方面，分离的IL-33结合剂可以是(1)抗体、替代支架、或其片段，以及(2)包含IL-33结合剂的蛋白或非蛋白部分的缀合物。例如，IL-33结合剂可以作为抗体的全部或部分缀合至肽、荧光分子或化疗剂。
IL-33结合剂可以是，或者可以获得自人抗体、非人抗体或嵌合抗体。“嵌合”是指包含人和非人区域的抗体或其片段。优选地，分离的IL-33结合剂是人源化抗体。“人源化”抗体是包含人抗体支架和获自或源自非人抗体的至少一个CDR的单克隆抗体。非人抗体包括分离自任意非人动物，例如啮齿类动物(例如，小鼠或大鼠)的抗体。人源化抗体可包含获自或源自非人抗体的一个、两个或三个CDR。在本发明的一个实施方式中，IL-33结合剂的CDRH3获自或源自小鼠单克隆抗体，而IL-33结合剂的其余可变区和恒定区获自或源自人单克隆抗体。
可以通过任意手段获得人抗体、非人抗体、嵌合抗体或人源化抗体，包括通过体外来源(例如，杂交瘤或细胞系重组产生抗体)和体内来源(例如，啮齿类动物)。用于产生抗体的方法是本领域所已知的，并描述在例如和Milstein，Eur.J.Immunol.，5:511-519(1976)；Harlow和Lane(编)，Antibodies:A Laboratory Manual，CSH Press(1988)；和Janeway等(编)，Immunobiology，第5版，Garland Publishing，New York，NY(2001))中。在某些实施方式中，可以使用转基因动物(例如，小鼠)生产人抗体或嵌合抗体，该动物中一个或多个内源性免疫球蛋白基因被一个或多个人免疫球蛋白基因所替代。内源性抗体基因被人抗体基因有效替代的转基因小鼠的实例包括但不限于，Medarex HUMAB-MOUSETM、KirinTC MOUSETM和Kyowa Kirin KM-MOUSETM(参见，例如，Lonberg，Nat.Biotechnol.，23(9):1117-25(2005)，以及Lonberg，Handb.Exp.Pharmacol.，181:69-97(2008))。可以使用本领域中已知的任何适当的方法生产人源化抗体(参见，例如，An,Z.(编)，TherapeuticMonoclonal Antibodies:From Bench to Clinic,John Wiley&Sons,Inc.，Hoboken，NewJersey(2009))，其包括例如，将非人CDR接合至人抗体支架(参见，例如，Kashmiri等，Methods，36(1):25-34(2005)；以及Hou等，J.Biochem.，144(1):115-120(2008))。在一个实施方式中，可以使用例如美国专利申请公开号2011/0287485A1中描述的方法产生人源化抗体。
在一个实施方式中，可以使用蛋白质化学或重组DNA技术将本文所述的免疫球蛋白重链多肽和/或免疫球蛋白轻链多肽的CDR(例如，CDR1、CDR2或CDR3)或可变区移植(即，接合)入另一分子，例如抗体或非抗体多肽。IL-33结合剂可包含如本文所述的免疫球蛋白重链和/或轻链多肽的至少一个CDR。分离的IL-33结合剂可包含如本文所述的免疫球蛋白重链和/或轻链可变区的一个、两个或三个CDR。例如，对于包含SEQ ID NO：1、SEQ ID NO：2或SEQ ID NO：5-50中任一的免疫球蛋白重链多肽，CDRl位于氨基酸残基26和35(包含本数)之间；CDR2位于氨基酸残基50和59(包含本数)之间(SEQ ID NO：1和SEQ ID NO：2)或氨基酸残基50和66(包含本数)之间(SEQ ID NO：5-50)；且CDR3位于氨基酸残基99和102(包含本数)之间(SEQ ID NO：1和SEQ ID NO：2)或氨基酸残基99和111(包含本数)之间(SEQ ID NO5-50)。对于包含SEQ ID NO：3、SEQ ID NO：4和SEQ ID NO：51-66中任一的免疫球蛋白轻链多肽，例如，CDRl位于氨基酸残基24和39(包含本数)之间(SEQ ID NO：3和SEQ ID NO：4)或氨基酸残基24和34(包含本数)之间(SEQ ID NO：51-66)；CDR2位于氨基酸残基55和61(包含本数)之间(SEQ ID NO：3和SEQ ID NO：4)或氨基酸残基50和56(包含本数)之间(SEQ IDNO：51-66)；CDR3位于氨基酸残基94和102(包含本数)之间(SEQ ID NO：3和SEQ ID NO：4)或氨基酸残基89和97(包含本数)之间(SEQ ID NO：51-66)。
术语“核酸序列”旨在包括DNA或RNA聚合物，即多核苷酸，其可以是单链的或双链的，并可含有非天然或改变的核苷酸。如本文所用的术语“核酸”和“多核苷酸”是指任意长度的核糖核苷酸(RNA)或脱氧核糖核苷酸(DNA)的核苷酸聚合形式。这些术语是指分子的一级结构，因此包括双链和单链DNA、以及双链和单链RNA。该术语包括作为等同物的由核苷酸类似物和经修饰多核苷酸(例如但不限于甲基化和/或加帽多核苷酸)构成的RNA或DNA类似物。核酸一般通过磷酸键连接以形成核酸序列或多核苷酸，虽然还有很多其他连接是本领域中已知的(例如，磷硫酰、硼磷酰等)。
可以使用编码多肽的核酸(任选地在载体中)提供包含一种或多种本文所述的免疫球蛋白重链和/或轻链的IL-33结合剂。载体可以是例如质粒、附加体(“episome”)、粘粒、病毒载体(例如，逆转录病毒或腺病毒载体)或噬菌体。适宜的载体和载体制备方法均是本领域所公知的(参见例如，Sambrook等，Molecular Cloning,a Laboratory Manual，第3版，Cold Spring Harbor Press，Cold Spring Harbor,N.Y.(2001)，以及Ausubel等，CurrentProtocols in Molecular Biology，Greene Publishing Associates and John Wiley&Sons，New York，N.Y.(1994))。
除了编码免疫球蛋白重链多肽、免疫球蛋白轻链多肽和/或IL-33结合剂的核酸序列以外，载体优选包含表达控制序列，例如启动子、增强子、多腺苷酸化信号、转录终止子、内部核糖体进入位点(IRES)等，提供其用于编码序列在宿主细胞内的表达。示例性的表达控制序列是本领域中已知的，并描述于例如Goeddel，Gene Expression Technology:Methods in Enzymology，Vol.185，Academic Press，San Diego，Calif.(1990)中。
来自多种不同来源的大量启动子(包括组成型、诱导型和可抑制启动子)均是本领域所公知的。启动子的代表性来源包括例如病毒、哺乳动物、昆虫、植物、酵母和细菌，并且来自这些来源的适宜启动子易于获得，或者可以基于可获得的公开序列通过合成制备，所述公开序列例如来自诸如ATCC以及其他商业或个人来源的保藏机构。启动子可以是单向的(即，在一个方向起始转录)或双向的(即，在3’或5’方向起始转录)。启动子的非限制性实例包括例如T7细菌表达系统、pBAD(araA)细菌表达系统、巨细胞病毒(CMV)启动子、SV40启动子、RSV启动子。诱导型启动子包括例如Tet系统(美国专利5,464,758和5,814,618)、蜕皮激素可诱导系统(No等，Proc.Natl.Acad.Sci.，93:3346-3351(1996))、T-REXTM系统(Invitrogen，Carlsbad，CA)、LACSWITCHTM系统(Stratagene，San Diego，CA)和Cre-ERT他莫昔芬可诱导重组酶系统(Indra等，Nuc.Acid.Res.，27:4324-4327(1999)；Nuc.Acid.Res.，28:e99(2000)；美国专利7,112,715；和Kramer&Fussenegger，Methods Mol.Biol.，308:123-144(2005))。
如本文所用的术语“增强子”是指增加例如与之可操作连接的核酸序列的转录的DNA序列。增强子可以位于核酸序列编码区的数千碱基以外，并且可以调节调控因子的结合、DNA甲基化的模式或DNA结构的改变。来自多种不同来源的大量增强子是本领域公知的，并可提供为克隆的多核苷酸或在克隆的多核苷酸内(来自例如，诸如ATCC以及其他商业或个人来源的保藏机构)。很多包含启动子(例如，常用的CMV启动子)的多核苷酸也包含增强子序列。增强子可以位于编码序列的上游、内部或下游。
载体还可以包含“选择标记基因”。如本文所用，术语“选择标记基因”是指这样的核酸序列，在存在相应选择剂时其使得表达该核酸序列的细胞被特异性地选择或针对。适宜的选择标记基因是本领域中已知的，并描述于例如国际专利申请公开WO 1992/008796和WO 1994/028143；Wigler等，Proc.Natl.Acad.Sci.USA，77:3567-3570(1980)；O'Hare等，Proc.Natl.Acad.Sci.USA，78:1527-1531(1981)；Mulligan&Berg，Proc.Natl.Acad.Sci.USA，78:2072-2076(1981)；Colberre-Garapin等，J.Mol.Biol.，150:1-14(1981)；Santerre等，Gene，30:147-156(1984)；Kent等，Science，237:901-903(1987)；Wigler等，Cell，11:223-232(1977)；Szybalska&Szybalski，Proc.Natl.Acad.Sci.USA，48:2026-2034(1962)；Lowy等，Cell，22:817-823(1980)；以及美国专利5,122,464和5,770,359中。
在一些实施方式中，载体是“附加体表达载体”或“附加体”，在存在适宜的选择性压力的情况下，其能够在宿主细胞中复制并作为DNA的染色体外片段持续存在于宿主细胞中(参见例如，Conese等，Gene Therapy，11:1735-1742(2004))。代表性的市售附加体表达载体包括但不限于使用Epstein Barr核抗原I(EBNAl)和Epstein Barr病毒(EBV)复制原点(oriP)的附加体质粒。来自Invitrogen(Carlsbad，CA)的载体pREP4、pCEP4、pREP7和pcDNA3.1以及来自Stratagene(La Jolla，CA)的pBK-CMV代表了替代EBNAl和oriP而使用T抗原和SV40复制原点的附加体载体的非限制性实例。
其他适宜的载体包括整合表达载体，其可以随机整合至宿主细胞的DNA、或可包括能够使表达载体和宿主细胞染色体之间特异性重组的重组位点。此类整合表达载体可以利用宿主细胞染色体的内源性表达控制序列以实现所需蛋白的表达。以位点特异性方式整合的载体的实例包括，例如来自Invitrogen(Carlsbad，CA)的flp-in系统的组件(例如，pcDNATM5/FRT)或cre-lox系统(例如，可见于来自Stratagene(La Jolla，CA)的pExchange-6核心载体)。随机整合至宿主细胞染色体的载体的实例包括，例如来自Life Technologies(Carlsbad，CA)的pcDNA3.1(当在缺乏T-抗原的情况下将其引入时)、来自Millipore(Billerica，MA)的UCOE以及来自Promega(Madison，WI)的pCI或pFN10A(ACT)FLEXITM。
还可以使用病毒载体。代表性的市售病毒表达载体包括但不限于，可购自Crucell公司(Leiden，荷兰)的基于腺病毒的Per.C6系统、来自Invitrogen(CarIsbad，CA)的基于慢病毒的pLPl以及来自Stratagene(La Jolla，CA)的逆转录病毒载体pFB-ERV加pCFB-EGSH。
可以将编码本文所述的氨基酸序列的核酸序列在相同载体上提供给细胞(即，顺式)。可以使用单向启动子以控制各核酸序列的表达。在另一实施方式中，可以使用双向和单向启动子的组合以控制多个核酸序列的表达。或者，可以将编码本文所述的氨基酸序列的核酸序列在分离载体上提供给细胞群(即，反式)。各分离载体中的各核酸序列可包含相同或不同的表达控制序列。可以同时或顺序地将分离载体提供给细胞。
可以将包含编码本文所述的氨基酸序列的核酸的载体引入能够表达由此所编码的多肽的宿主细胞，包括任意适宜的原核或真核细胞。优选的宿主细胞是能够容易并稳定地生长，具有相当迅速的生长速率，具有良好表征的表达系统，并且能够被方便和有效地转化或转染的那些细胞。
适宜的原核细胞的实例包括但不限于来自杆菌属(如枯草芽孢杆菌和短小芽孢杆菌)、埃希氏杆菌属(如大肠杆菌)、假单胞菌属、链霉菌属、沙门氏菌属和欧文氏菌属的细胞。特别有用的原核细胞包括大肠杆菌的不同菌株(例如，K12、HB101(ATCC编号33694)、DH5α、DH10、MC1061(ATCC编号53338)和CC102)。
优选地，将载体引入真核细胞。适宜的真核细胞是本领域中已知的，并且包括例如酵母细胞、昆虫细胞和哺乳动物细胞。适宜酵母细胞的实例包括来自克鲁维酵母菌属、毕赤酵母属、鼻孢子虫属、酵母菌属和裂殖酵母属的那些。优选的酵母细胞包括例如酿酒酵母和毕赤酵母。
适宜的昆虫细胞描述于例如Kitts等，Biotechniques，14:810-817(1993)；Lucklow，Curr.Opin.Biotechnol.，4:564-572(1993)；和Lucklow等，J.Virol.，67:4566-4579(1993)中。优选的昆虫细胞包括Sf-9和HI5(Invitrogen，Carlsbad，CA)。
优选地，利用哺乳动物细胞。多种适宜的哺乳动物宿主细胞是本领域中已知的，并且多种可以从美国典型培养物保藏中心(ATCC，Manas sas，VA)获得。适宜的哺乳动物细胞的实例包括但不限于中国仓鼠卵巢细胞(CHO)(ATCC编号CCL61)、CHO DHFR细胞(Urlaub等，Proc.Natl.Acad.Sci.USA，97:4216-4220(1980))、人胚胎肾(HEK)293或293T细胞(ATCC编号CRL1573)和3T3细胞(ATCC编号CCL92)。其他适宜的哺乳动物细胞系为猴COS-1(ATCC编号CRL1650)和COS-7细胞系(ATCC编号CRL1651)、以及CV-1细胞系(ATCC编号CCL70)。进一步的示例性哺乳动物宿主细胞包括灵长类细胞系和啮齿类细胞系，包括转化细胞系。正常的二倍体细胞，来自原代组织体外培养的细胞系，以及原代外植体也是适宜的。其他适宜的哺乳动物细胞系包括但不限于小鼠神经母细胞瘤N2A细胞、HeLa、小鼠L-929细胞、和BHK或HaK仓鼠细胞系，其全部均可以从ATCC获得。选择适宜的哺乳动物宿主细胞以及转化、培养、扩增、筛选和纯化细胞的方法均是本领域中已知的。
更优选地，哺乳动物细胞是人类细胞。例如，哺乳动物细胞可以是人类淋巴或淋巴来源细胞系，例如前B淋巴细胞来源细胞系。人类淋巴细胞系的实例包括但不限于RAMOS(CRL-1596)、Daudi(CCL-213)、EB-3(CCL-85)、DT40(CRL-2111)、18-81(Jack等，Proc.Natl.Acad.Sci.USA，85:1581-1585(1988))、Raji细胞(CCL-86)及其衍生物。
可以通过“转染”、“转化”或“转导”将编码氨基酸序列的核酸序列引入细胞。如本文所用的“转染”、“转化”或“转导”是指通过使用物理或化学方法将一个或多个外源性多核苷酸引入宿主细胞。多种转染技术均是本领域中已知的，且包括例如磷酸钙DNA共沉淀(参见例如，Murray E.J.(编)，Methods in Molecular Biology，Vol.7，Gene Transfer andExpression Protocols，Humana Press(1991))；DEAE_葡聚糖；电穿孔；阳离子脂质体介导的转染；钨粒子促化微粒轰击(Johnston，Nature，346:776-777(1990))；和磷酸锶DNA共沉淀(Brash等，Mol.Cell Biol.，7:2031-2034(1987))。当感染性粒子在适宜的包装细胞(许多包装细胞是市售的)中生长后，可以将噬菌体或病毒载体引入宿主细胞。
IL-33抑制剂可以作为组合物的一部分施用。优选地，该组合物是药学上可接受的(例如，生理学上可接受的)组合物，并包含运载体，优选药学上可接受的(例如，生理学上可接受的)运载体。在本发明的背景中可以使用任何适当的运载体，并且此类运载体是本领域所公知的。通过组合物施用的特定部位以及施用组合物所使用的特定方法来部分地确定载体的选择。组合物任选地可以是无菌的。组合物可以冷冻或冻干贮存并在使用前在适当的无菌运载体中重构。可以根据常规技术生产组合物，其描述于例如Remington:The Scienceand Practice of Pharmacy，第21版，Lippincott Williams&Wilkins，Philadelphia，PA(2001)中。
如本文所用，术语“疗法”、“治疗”等是指获得所需的药理学和/或生理学效应，例如抑制或预防过敏反应。优选地，该效应是治疗性的，即该效应部分或完全治愈疾病和/或归因于该疾病的不良症状。为了这个目的，本发明方法包括施用“治疗有效量”的IL-33抑制剂。“治疗有效量”是指在必要的剂量和时间段内有效达到所需治疗结果的量。治疗有效量会根据诸如以下的因素而改变：个体的疾病状态、年龄、性别和体重，以及IL-33抑制剂在该个体中激发所需应答的能力。例如，组合物的治疗有效量是降低哺乳动物或人类中的IL-33生物活性的量。
或者，药理学和/或生理学效应可能是预防性的，即该效应完全或部分预防疾病或其症状。在此方面，本发明方法包括施用“预防有效量”的IL-33抑制剂。“预防有效量”指在必要的剂量和时间段内有效达到所需预防结果(例如，预防疾病发作)的量。
典型剂量可以例如在1pg/kg至20mg/kg动物或人体重量的范围内；然而，低于或高于该示例性范围的剂量仍在本发明的范围内。每日肠胃外剂量可以是约0.00001μg/kg至约20mg/kg总体重(例如，约0.001μg/kg、约0.1μg/kg、约1μg/kg、约5μg/kg、约10μg/kg、约100μg/kg、约500μg/kg、约1mg/kg、约5mg/kg、约10mg/kg，或前述值中任意两个所定义的范围)，优选从约0.1μg/kg至约10mg/kg总体重(例如，约0.5μg/kg、约1μg/kg、约50μg/kg、约150μg/kg、约300μg/kg、约750μg/kg、约1.5mg/kg、约5mg/kg，或前述值中任意两个所定义的范围)，更优选从约1μg/kg至5mg/kg总体重(例如，约3μg/kg、约15μg/kg、约75μg/kg、约300μg/kg、约900μg/kg、约2mg/kg、约4mg/kg，或前述值中任意两个所定义的范围)，且甚至更优选约0.5至15mg/kg体重/天(例如，约1mg/kg、约2.5mg/kg、约3mg/kg、约6mg/kg、约9mg/kg、约11mg/kg、约13mg/kg，或前述值中任意两个所定义的范围)。可以通过定期对接受治疗的患者进行评估以监测治疗或预防功效。对于持续若干天或更长时间的重复施用而言，依据情况，重复治疗直至疾病症状出现所需的抑制。然而，其他剂量方案可能是有用的，并且在本发明的范围内。可以通过将组合物单次团注施用、通过将组合物多次团注施用、或通过将组合物连续输注施用以递送所需的剂量。
可以使用标准施用技术向哺乳动物施用IL-33抑制剂，所述标准施用技术包括口服、静脉、腹腔、皮下、肺部、透皮、肌内、鼻内、口腔、舌下、或栓剂施用。该组合物优选适于肠胃外施用。如本文所用，术语“肠胃外”包括静脉、肌内、皮下、直肠、阴道和腹腔施用。更优选地，通过静脉、腹腔或皮下注射使用外周系统递送将组合物施用于哺乳动物。
还可以通过将编码IL-33抑制剂的核酸引入哺乳动物来施用IL-33抑制剂，由此IL-33抑制剂在哺乳动物中表达。编码IL-33抑制剂的核酸可以在载体中，如本文关于其他实施方式所述。此外，编码IL-33抑制剂的核酸可以直接施用于哺乳动物，或施用于细胞(例如，自体细胞)以提供表达IL-33抑制剂的转化细胞，然后可将该转化细胞施用于哺乳动物。另外或或者，可以通过引入或删除调节IL-33表达的遗传物质来实现IL-33抑制。用于向哺乳动物和细胞施用核酸以表达蛋白质的技术，用于转化细胞和将转化细胞施用于哺乳动物的技术，以及用于删除遗传物质的技术均是本领域中已知的。
一旦施用于哺乳动物(例如，可交叉反应的人)，可以通过本领域已知的任何适当方法测定IL-33抑制剂的生物活性。例如，可以通过测定特定IL-33抑制剂的稳定性来评估生物活性。在本发明的一个实施方式中，IL-33抑制剂(例如，抗体)的体内半衰期介于约30分钟至45天之间(例如，约30分钟、约45分钟、约1小时、约2小时、约4小时、约6小时、约10小时、约12小时、约1天、约5天、约10天、约15天、约25天、约35天、约40天、约45天，或前述值中任意两个所定义的范围)。在另一实施方式中，IL-33抑制剂的体内半衰期介于约2小时至20天之间(例如，约5小时、约10小时、约15小时、约20小时、约2天、约3天、约7天、约12天、约14天、约17天、约19天，或前述值中任意两个所定义的范围)。在另一实施方式中，IL-33抑制剂的体内半衰期介于约10天至约40天之间(例如，约10天、约13天、约16天、约18天、约20天、约23天、约26天、约29天、约30天、约33天、约37天、约38天、约39天、约40天，或前述值中任意两个所定义的范围)。
还可以通过测定特定IL-33结合剂与IL-33或其表位的结合亲和力来评估其生物活性。术语“亲和力”是指两个试剂可逆结合的平衡常数，且其以解离常数(KD)表示。结合剂与配体的亲和力(如抗体与表位的亲和力)可以是例如从约1飞摩尔(fM)至约100微摩尔(μM)(例如，约1fM至约1皮摩尔(pM)、约1pM至约1纳摩尔(nM)、约1nM至约1微摩尔(μM)，或约1μM至约100μM)。在一个实施方式中，IL-33结合剂可以以小于或等于1纳摩尔的KD(例如，0.9nM、0.8nM、0.7nM、0.6nM、0.5nM、0.4nM、0.3nM、0.2nM、0.1nM、0.05nM、0.025nM、0.01nM、0.001nM，或前述值中任意两个所定义的范围)结合IL-33蛋白。在另一实施方式中，IL-33结合剂可以以小于或等于200pM的KD(例如，190pM、175pM、150pM、125pM、110pM、100pM、90pM、80pM、75pM、60pM、50pM、40pM、30pM、25pM、20pM、15pM、10pM、5pM、1pM，或前述值中任意两个所定义的范围)结合IL-33。可使用本领域已知的任意试验测量针对目标抗原或表位的免疫球蛋白亲和力。此类方法包括例如荧光活化细胞分选(FACS)、可分离小珠(例如，磁珠)、表面等离子共振(SPR)、溶液相竞争(KINEXATM)、抗原筛选(“panning”)和/或ELISA(参见例如，Janeway等(编)，Immunobiology，第5版，Garland Publishing，New York，NY，2001)。
在本发明的一个实施方式中，提供了预防性治疗先前被诊断患有过敏反应的患者的方法，所述过敏反应包括但不限于对花生的过敏反应，所述方法包括在暴露于过敏原(例如，花生过敏原)或过敏反应(例如，对花生过敏原的过敏反应)发生之前向患者施用IL-33抑制剂。换言之，根据该实施方式，当患者未表现出过敏反应时，将IL-33抑制剂施用于患有已知过敏症的患者。该方法可以进一步包括，不考虑治疗之间花生过敏症状是否发生，作为预防性治疗用抗IL-33抑制剂定期治疗患者以缓和意外暴露于花生过敏原时对花生的过敏反应。因此，在这种情况下的“预防性”治疗不需要完全预防，而是仅在某种程度上减轻过敏反应或其症状的严重性。可以使用任何适宜的IL-33抑制剂施用频率，例如每日、每周、每两周、每月、每两月或每三月一次。一旦这样的患者暴露于过敏原(例如，花生过敏原)，在暴露于花生之前在患者的血流和/或组织内存在IL-33抑制剂旨在抑制这种暴露后的过敏反应和潜在的过敏性休克。
在另一实施方式中，该方法包括将IL-33抑制剂施用于先前被诊断患有过敏反应(包括但不限于对花生的过敏反应)的患者，此时暴露于花生过敏原是可能发生的，或者一旦认为已经发生或已经实际发生暴露于花生过敏原，但是在过敏性休克发作之前(例如，在过敏性休克的临床表现之前)。过敏性休克的发作的确定是在普通医师的技能范围内，并且包括例如暴露于过敏原后症状的发作，包括呼吸受损、咽喉肿胀、血压突然下降、皮肤苍白或嘴唇发白、昏厥和/或头晕。IL-33抑制剂的施用可以是自我施用。例如，患者可以根据需要随身携带抗IL-33抑制剂治疗进行按需施用，可能是在预期花生过敏原暴露为潜在风险的情况下，或者一旦认为可能已经发生暴露。因此，IL-33抑制剂是在自动注射装置(如弹簧加载的自动注射器)中，对着皮肤按下按钮或按压装置时其自动地将针插入患者的皮肤中并且通过针来施用药物。
IL-33抑制剂可以单独或与其他药物(例如，作为佐剂)联合施用。例如，可以使用其他用于治疗或预防过敏反应的药剂。此类药剂包括抗组胺药、其他抗炎药，例如皮质类固醇(如泼尼松和氟替卡松)和非甾体抗炎药(NSAID)(如阿司匹林、布洛芬和萘普生)。
以下实施例旨在说明本发明，但并不限制另外描述的本发明的范围。
实施例1
产生了具有上述功能特征的抑制IL-33信号传导的抗IL-33抗体，并在食蟹猴中进行为期4周和13周的多剂量GLP顺应性毒理学研究测试，随后在每种情况下有8周的恢复期。结果显示IL-33中和剂在食蟹猴中具有良好的耐受性，没有计划外的牺牲或显著的治疗相关作用。对下述安全药理学参数没有顾虑：本研究中评估的CNS、心血管和呼吸功能。在任何测试剂量水平下施用中和剂后无肉眼可见或组织病理学副作用。
实施例2
在人体首次(first-in-human)、单次递增剂量和多次递增剂量、1期临床研究中测试如本文所述的中和抗IL-33抗体。在10mg至750mg的宽剂量范围内向总共72名健康志愿者给予IL-33中和剂。没有观察到剂量限制性毒性，并且IL-33中和剂被良好耐受。
在不同时间点自患者收集血液样品，并在用IL-33刺激后在全血离体测定中测试IL-33抑制活性，并测量IL-33抑制剂对IFN释放的抑制。观察到长达至少3个月的持续和几乎完全的抑制。
实施例3
实施例1和2中描述的在GLP毒理学研究中产生的数据和来自1期临床研究的数据支持在患有特应性疾病如花生过敏的患者中启动2期研究。IL-33抑制剂的治疗活性将在患有花生过敏的成年患者中进行测试。在筛选访视时，根据PRACTALL共识报告，每个适格的患者将接受分级花生和安慰剂口服食物挑战(BPCFC)。根据PRACTALL指南，使用口服食物挑战(OFC)症状评分评估工具监测BPCFC期间的主观症状。将记录在反应之前达到的盲法花生/安慰剂耐受的总累积剂量和给药步骤/阈值。在首次BPCFC之后，适格患者将随机接受IL-33抑制剂或安慰剂。然后根据PRACTALL指南，患者将接受第二次花生和安慰剂口服食物挑战。将使用OFC症状评分评估工具监测症状，并将进行其他安全性评估。将记录在反应之前达到的盲法花生/安慰剂耐受的总累积剂量和给药步骤/阈值。使用协方差混合效应分析(ANCOVA)比较IL-33抑制剂和安慰剂之间的自基线改变、首次BPCFC、耐受剂量和OFC评分。根据PRACTALL指南，与安慰剂相比，IL-33抑制剂治疗患者的耐受性改善将决定花生过敏患者中IL-33抑制的活性。
本文中引用的所有参考文献，包括出版物、专利申请和专利，都在此通过引用并入，对每篇参考文献的引用都如同单独地和具体地指出其通过引用的方式并入，并且在本文中将其完整地列出的相同程度。
在本发明描述的上下文中(特别是在随后的权利要求书的上下文中)，除非在本文中另有说明或者与上下文明显矛盾，术语“一(a)”和“一个(an)”和“所述(the)”和“至少一个(种)”以及相似指示词的使用应理解为包括单数和复数。除非在本文中另有说明或者与上下文明显矛盾，后接一项或多项列表的术语“至少一种”的使用(例如，“至少一种A和B”)应理解为表示选自所列项的一项(A或B)或者所列项中两项或更多项的任意组合(A和B)。除非另有注明，术语“包含”、“具有”、“包括”以及“含有”都应理解为开放式术语(即，意思是“包括，但不限于”)。除非在本文中另有说明，本文中对数值范围的描述仅仅旨在作为对每个落在该范围内的单个数值的单独引用的简略写法，且每个单个数值以如同在本文中单独引用的方式并入本说明书。除非在本文中另有说明或者与上下文明显矛盾，所有在本文中描述的方法都可以按照任何适当的顺序进行。除非另有要求，在本文中提供的任何和所有实施例或示例性语言(如，“例如”)的使用，都仅仅旨在更好地阐明本发明，而不是在本发明的范围上加以限制。说明书中的任何语言都不应被理解为用于表明任何未要求的要素为实施本发明所必需。
本文描述了本发明的优选实施方式，包括发明人所知晓的实施本发明的最佳方式。在对上述说明书进行阅读的基础上，那些优选实施方式的变体对本领域普通技术人员而言可为显而易见的。发明人预期熟练技术人员可以根据需要应用这样的变体，且发明人有意以本文中具体描述的方式以外的方式实施本发明。因此，本发明包括由适用法律所准许的本发明所附权利要求中所述主题的所有修饰和等同。而且，除非在本文中另有说明或者与上下文明显矛盾，本发明包括以上所述要素的所有可能的变体的任意组合。
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<110> 安奈普泰斯生物有限公司
M·隆代伊
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Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 8
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 8
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 Ser Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 9
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 9
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 His Ser Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 10
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 10
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 Ser Ser Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 11
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 11
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 Ala Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 12
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 12
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 Gly Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 13
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 13
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 Asn Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 14
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 14
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 Thr Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 15
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 15
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 Phe
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 16
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 16
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 His
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 17
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 17
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln His Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 18
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 18
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Phe Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 19
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 19
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Leu Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 20
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 20
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Asn Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 21
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 21
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Val Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 22
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 22
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Asn Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 23
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 23
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Thr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 24
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 24
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Ile Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 25
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 25
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Asn Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 26
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 26
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Arg Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 27
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 27
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Val Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 28
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 28
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Ser Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 29
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 29
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Asn Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 30
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 30
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Thr Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 31
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 31
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 32
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 32
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 33
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 33
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 34
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 34
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 35
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 35
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 36
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 36
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Ile Tyr Tyr Cys
85 90 95
Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 37
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 37
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Ile Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 38
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 38
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
Phe Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 39
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 39
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Asp Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 40
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 40
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Arg Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 41
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 41
Gln Val Gln Leu Val Glu 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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 42
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 42
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 Asp Tyr
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 43
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 43
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
Trp Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 44
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 44
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
Trp Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 45
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 45
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
Trp Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 46
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 46
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Phe Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 47
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 47
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp His Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 48
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 48
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
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Thr 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 49
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 49
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 His
20 25 30
Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys Phe
50 55 60
Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Ile Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val
115 120
<210> 50
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 50
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
Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val 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 Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 51
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 51
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 52
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 52
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Val Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 53
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 53
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ile Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 54
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 54
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 55
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 55
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 56
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 56
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 57
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 57
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ser Thr Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 58
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 58
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ser Ala Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 59
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 59
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Arg Thr Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 60
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 60
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Arg Ala Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 61
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 61
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Lys Thr Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 62
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 62
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ala Ala Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 63
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 63
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Thr Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 64
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 64
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ala Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 65
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 65
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr Ala
20 25 30
Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Tyr Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 66
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 66
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Ser Ser Tyr
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Ser Tyr Pro Phe
85 90 95
Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 67
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 67
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 68
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 68
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 69
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 69
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys
65 70 75 80
Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 70
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 70
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Ala
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 71
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 71
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Asp Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 72
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 72
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Thr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 73
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 73
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Asn Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 74
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 74
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Asp Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 75
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 75
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 76
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 76
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Phe Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 77
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 77
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Gly
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 78
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 78
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ala
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 79
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 79
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 80
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 80
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Thr
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 81
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 81
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
His Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 82
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 82
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln His Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 83
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 83
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Ile Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 84
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 84
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Asn Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 85
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 85
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Thr Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 86
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 86
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Arg Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 87
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 87
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Ser Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 88
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 88
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe His Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 89
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 89
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Ser Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 90
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 90
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 91
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 91
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Val Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 92
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 92
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Asn Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 93
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 93
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 94
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 94
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Ser Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 95
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 95
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Phe Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 96
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 96
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Asn Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 97
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 97
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Leu Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 98
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 98
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Val Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 99
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 99
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Phe Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 100
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 100
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Ile Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 101
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 101
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Arg
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 102
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 102
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Asn
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 103
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 103
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Arg Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 104
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 104
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Thr
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 105
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 105
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Glu Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 106
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 106
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 107
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 107
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 108
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 108
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Leu His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 109
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 109
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 110
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 110
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp His Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 111
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 111
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Phe Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 112
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 112
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Ile Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 113
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 113
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
His Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Ile Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 114
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 114
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Ile Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 115
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 115
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 116
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 116
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 117
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 117
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Asp Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 118
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 118
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Phe Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 119
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 119
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Ala Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 120
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 120
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Gly Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 121
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 121
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 122
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 122
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Val
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 123
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 123
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Pro
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 124
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 124
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 125
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 125
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 126
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 126
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 127
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 127
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 128
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 128
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Ile Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 129
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 129
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Ile Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 130
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 130
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 131
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 131
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 132
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 132
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 133
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 133
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 134
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 134
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 135
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 135
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 136
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 136
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 137
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 137
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 138
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 138
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 139
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 139
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 140
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 140
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Met Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Met Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asn Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Leu Thr Ser Pro Pro Thr Leu Phe
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 141
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 141
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 142
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 142
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 143
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 143
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 144
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 144
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 145
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 145
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Val Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 146
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 146
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ile Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 147
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 147
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Leu Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 148
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 148
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 149
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 149
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 150
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 150
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ser Thr Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 151
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 151
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Ser Ala Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 152
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 152
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Arg Thr Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 153
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 153
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Arg Ala Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 154
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 154
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Lys Thr Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 155
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 155
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Lys Ala Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 156
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 156
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Thr Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 157
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 157
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ala Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 158
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 158
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Ser Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 159
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 159
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Thr Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 160
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 160
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Phe Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 161
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 161
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ala Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 162
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 162
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Pro Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 163
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 163
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Thr Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 164
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 164
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala His Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 165
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 165
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Asn Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 166
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 166
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Tyr Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 167
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 167
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Arg Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 168
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 168
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 169
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 169
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser
35 40 45
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 170
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 170
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser
35 40 45
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Asn Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 171
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 171
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asp Val Gly Thr
35 40 45
Ala Val Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Trp Ala Ser Thr Arg His Thr Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Lys Thr Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 172
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 172
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser
35 40 45
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Asn Asn Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 173
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 173
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser
35 40 45
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Ser Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ala Gln Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 174
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 174
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser
35 40 45
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Phe Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Ser Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 175
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 175
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val
20 25 30
Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Gly Ile Arg Ser
35 40 45
Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu
50 55 60
Ile Tyr Val Ala Phe Thr Leu Gln Ser Gly Val Pro Ser Arg Phe Ser
65 70 75 80
Gly Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln
85 90 95
Pro Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Cys Asn Asn Tyr Pro
100 105 110
Phe Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
115 120 125
<210> 176
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 176
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Tyr Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Thr Ile Tyr Pro Arg Asn Ser Asp Thr Asp Tyr Asn Gln Lys
65 70 75 80
Phe Lys Ala Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 177
<211> 139
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 177
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly
20 25 30
Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser
35 40 45
Tyr Trp Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp
50 55 60
Met Gly Ile Ile Asn Pro Ser Gly Gly Ser Thr Ser Tyr Ala Gln Lys
65 70 75 80
Phe Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val
85 90 95
Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr
100 105 110
Cys Ala Arg Pro Leu Tyr Tyr Tyr Val Thr Ser Pro Pro Thr Leu Leu
115 120 125
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
130 135
<210> 178
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 178
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn
85 90 95
Ser Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Asp Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 179
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 179
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Glu Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Ser
85 90 95
Ser Leu Tyr Leu Gln Met Asn Asn Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Asp Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 180
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 180
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Asp Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 181
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 181
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Ser
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Asp Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 182
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 182
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Asp Ala Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 183
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 183
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Asp Ser Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 184
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 184
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Gly Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 185
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 185
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Ser Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 186
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 186
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Thr Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 187
<211> 144
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 187
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Glu Val Gln Leu Val Glu Ser Gly Gly Gly Leu Val Gln Pro Gly
20 25 30
Gly Ser Leu Arg Leu Ser Cys Val Ala Ser Gly Phe Thr Phe Ser Asn
35 40 45
Tyr Trp Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp
50 55 60
Val Ala Asp Ile Arg Leu Lys Ser Asn Asn Tyr Ala Thr His Tyr Ala
65 70 75 80
Glu Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asp Ala Lys Asn
85 90 95
Ser Val Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Val Arg Met Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val
115 120 125
Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
130 135 140
<210> 188
<211> 125
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 188
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
Trp Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Asn Ile Lys Gln Asp Gly Ser Glu Lys Tyr Tyr Val Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ala Lys Asn Ser Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Val Arg Asp Gly Pro Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser
100 105 110
Ala Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala
115 120 125
<210> 189
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 189
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His Ser
20 25 30
Asn Gly Asn Thr Tyr Leu Glu Trp Phe Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Arg Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln Gly
85 90 95
Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 190
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 190
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Leu Val Tyr
35 40 45
Ser Asp Gly Asn Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Arg Leu Ile Tyr Lys Val Ser Asn Arg Asp Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 191
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 191
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Leu Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 192
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 192
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Leu Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 193
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 193
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 194
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 194
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Gln Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 195
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 195
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Leu Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 196
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 196
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Ala Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 197
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 197
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Ser Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 198
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 198
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Glu Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 199
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 199
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Thr Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 200
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 200
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Ala Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 201
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 201
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Asp Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 202
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 202
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Phe Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 203
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 203
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Val Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 204
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 204
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Leu Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 205
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 205
Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu
1 5 10 15
Ala Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu
20 25 30
Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Gln Ser Ile Val His
35 40 45
Ser Asn Gly Asn Thr Tyr Leu Glu Trp Tyr Gln Gln Arg Pro Gly Gln
50 55 60
Ser Pro Arg Leu Leu Ile Tyr Lys Ile Ser Asn Arg Phe Ser Gly Val
65 70 75 80
Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys
85 90 95
Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Phe Gln
100 105 110
Gly Ser His Val Pro Arg Thr Phe Gly Gly Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 206
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 206
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 207
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 207
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Ala Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Asn Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Phe Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Ser Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 208
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 208
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Ser Tyr Val Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 209
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 209
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Phe Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 210
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 210
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Phe Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Ser Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 211
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 211
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 212
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 212
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Ser Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 213
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 213
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Phe Lys Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Ser Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 214
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 214
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 215
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 215
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Ser Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 216
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 216
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 217
<211> 153
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 217
Met Glu Phe Gly Leu Ser Trp Val Phe Leu Val Ala Leu Leu Arg Gly
1 5 10 15
Val Gln Cys Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln
20 25 30
Pro Gly Arg Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Phe
35 40 45
Ser Asn Tyr Val Met His Trp Val Arg Gln Thr Pro Gly Lys Gly Leu
50 55 60
Glu Trp Val Ala Val Ile Ser Tyr Asp Gly Arg Asn Lys Tyr Tyr Ala
65 70 75 80
Asp Ser Val Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Asn Asn
85 90 95
Thr Leu Tyr Leu Gln Met Asn Ser Leu Arg Ala Asp Asp Thr Ala Val
100 105 110
Tyr Tyr Cys Ala Lys Ala Pro Gly Pro Met Val Arg Gly Val Ile Pro
115 120 125
Asp Ile Trp Gly Gln Gly Thr Met Val Thr Val Ser Ser Gly Ser Ala
130 135 140
Ser Ala Pro Thr Leu Phe Pro Leu Ala
145 150
<210> 218
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 218
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
35 40 45
Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Gly
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 219
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 219
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
35 40 45
Val Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Gly
100 105 110
Thr His Trp Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 220
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 220
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Arg Ser Ser Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Val
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 221
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 221
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Arg Ser Ser Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Val
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Thr Ser Ile Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 222
<211> 147
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 222
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Arg Ser Ser Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Val
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Thr Ser Ile Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro 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
145
<210> 223
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 223
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
35 40 45
Val Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Thr
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Thr Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Gly
100 105 110
Thr His Trp Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 224
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 224
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
35 40 45
Val Ile Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Thr Ser Ile Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Gly
100 105 110
Thr His Trp Leu Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 225
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 225
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Arg Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 226
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 226
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Arg Ser Ser Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 227
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 227
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Ser Ser Ser Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 228
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 228
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Ser Ser Ser Tyr Leu Gly Trp Tyr Gln Gln Lys Pro Gly Gln Val
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 229
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 229
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Val
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 230
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 230
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Thr Ser Gln Ser
35 40 45
Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130
<210> 231
<211> 130
<212> PRT
<213> 人工序列
<220>
<223> 合成序列
<400> 231
Met Glu Thr Pro Ala Gln Leu Leu Phe Leu Leu Leu Leu Trp Leu Pro
1 5 10 15
Asp Thr Thr Gly Glu Ile Val Leu Thr Gln Ser Pro Gly Thr Leu Ser
20 25 30
Leu Ser Pro Gly Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Gln Ser
35 40 45
Val Ser Ser Ser Tyr Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala
50 55 60
Pro Arg Leu Leu Ile Tyr Gly Ala Ser Ser Arg Ala Thr Gly Ile Pro
65 70 75 80
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
85 90 95
Ser Arg Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ala
100 105 110
Thr His Trp Pro Pro Tyr Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile
115 120 125
Lys Arg
130

Claims (23)

1.一种抑制或预防哺乳动物中的过敏反应的方法，其包括向所述哺乳动物施用IL-33抑制剂。
2.权利要求1所述的方法，其中所述过敏反应是食物过敏。
3.权利要求1所述的方法，其中所述过敏反应是哮喘、特应性皮炎或其组合。
4.权利要求2所述的方法，其中所述食物过敏是坚果过敏、花生过敏、贝类过敏、鱼过敏、奶过敏、蛋过敏、小麦过敏或大豆过敏。
5.权利要求1-4中任一项所述的方法，其中所述IL-33抑制剂是抗IL-33抗体或抗体片段。
6.权利要求5所述的方法，其中所述抗IL-33抗体或抗体片段包含分离的免疫球蛋白重链多肽，其包括(a)SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中任一的氨基酸序列，(b)与SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中任一具有至少90％同一性的氨基酸序列；或(c)免疫球蛋白重链多肽，其与(a)或(b)的免疫球蛋白重链多肽结合相同的IL-33表位。
7.权利要求5或6所述的方法，其中所述抗IL-33抗体或抗体片段包含分离的免疫球蛋白轻链多肽，其包括(d)SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ ID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中任一的氨基酸序列，(e)与SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ ID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中任一具有至少90％同一性的氨基酸序列；或(f)免疫球蛋白轻链多肽，其与(d)或(e)的免疫球蛋白轻链多肽结合相同的IL-33表位。
8.权利要求1-7中任一项所述的方法，其中所述IL-33抑制剂是F(ab’)2、Fab’、Fab、Fv、scFv、dsFv、dAb或单链结合多肽。
9.权利要求1-8中任一项所述的方法，其中所述IL-33抑制剂包含SEQ ID NO：136的免疫球蛋白重链多肽和SEQ ID NO：171的免疫球蛋白轻链多肽。
10.权利要求1-5中任一项所述的方法，其中所述分离的IL-33抑制剂包含免疫球蛋白重链可变区的至少一个互补决定区(CDR)，所述免疫球蛋白重链可变区包括SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ ID NO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQID NO：178-188和SEQ ID NO：206-217中的任一。
11.权利要求10所述的方法，其中所述IL-33抑制剂包含免疫球蛋白重链可变区的一个CDR，所述免疫球蛋白重链可变区包括SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ IDNO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中的任一。
12.权利要求10所述的方法，其中所述IL-33抑制剂包含免疫球蛋白重链可变区的两个CDR，所述免疫球蛋白重链可变区包括SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ IDNO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中的任一。
13.权利要求10所述的方法，其中所述IL-33抑制剂包含免疫球蛋白重链可变区的三个CDR，所述免疫球蛋白重链可变区包括SEQ ID NO：1、SEQ ID NO：2、SEQ ID NO：5-50、SEQ IDNO：67-140、SEQ ID NO：176、SEQ ID NO：177、SEQ ID NO：178-188和SEQ ID NO：206-217中的任一。
14.权利要求1-5中任一项所述的方法，其中所述分离的IL-33抑制剂包含免疫球蛋白轻链可变区的至少一个CDR，所述免疫球蛋白轻链可变区包括SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQ ID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中的任一。
15.权利要求14所述的方法，其中所述IL-33抑制剂包含免疫球蛋白轻链可变区的一个CDR，所述免疫球蛋白轻链可变区包括SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中的任一。
16.权利要求14所述的方法，其中所述IL-33抑制剂包含免疫球蛋白轻链可变区的两个CDR，所述免疫球蛋白轻链可变区包括SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中的任一。
17.权利要求14所述的方法，其中所述IL-33抑制剂包含免疫球蛋白轻链可变区的三个CDR，所述免疫球蛋白轻链可变区包括SEQ ID NO：3、SEQ ID NO：4、SEQ ID NO：51-66、SEQID NO：141-175、SEQ ID NO：189-205和SEQ ID NO：218-231中的任一。
18.权利要求1-17中任一项所述的方法，其中所述IL-33抑制剂在所述哺乳动物中的半衰期是在30分钟至45天之间。
19.权利要求1-18中任一项所述的方法，其中所述IL-33抑制剂以约1飞摩尔(fM)至约100微摩尔(μM)之间的KD结合IL-33。
20.权利要求1-19中任一项所述的方法，其中哺乳动物具有增加IL-33表达或信号传导的突变。
21.权利要求1-19中任一项所述的方法，其中用抗IL-33抑制剂定期治疗所述哺乳动物以作为预防性治疗。
22.权利要求1-19中任一项所述的方法，其中当暴露于过敏原已经发生或怀疑已经发生时，用抗IL-33抑制剂治疗所述哺乳动物。
23.一种用于治疗过敏反应的药物组合物，其包含IL-33抑制剂。
CN201780014394.8A 2016-01-14 2017-01-17 使用il-33抑制剂抑制过敏反应 Pending CN109475622A (zh)

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