CN111741977A - 转铁蛋白受体结合性多肽和其用途 - Google Patents
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Abstract
本公开总体上涉及如下Fc多肽二聚体，所述Fc多肽二聚体含有非天然转铁蛋白受体(TfR)结合位点，不大体上消耗体内网织红细胞，但保持结合于Fcg受体(FcgR)。本公开还涉及一种如下Fc多肽二聚体，所述Fc多肽二聚体含有所述Fc多肽中的一者上的特异性结合TfR的非天然位点；对含有所述TfR结合位点的所述Fc多肽的当结合于TfR时减少FcgR结合的一个修饰或多个修饰，其中另一Fc多肽不含TfR结合位点，但保持FcgR结合。
Description
相关申请的交叉引用
本申请要求于2018年1月10日提交的美国临时专利申请号62/615,914、于2018年2月15日提交的美国临时专利申请号62/631,281、于2018年6月8日提交的美国临时专利申请号62/682,639以及于2018年8月22日提交的美国临时专利申请号62/721,275的优先权，所述临时专利申请的公开内容出于所有目的以全文引用的方式并入本文中。
技术领域
本公开涉及被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体结合转铁蛋白受体(TfR)，可诱导至少一种效应功能活性(例如抗体依赖性细胞毒性(ADCC))，但不引起网织红细胞的实质性消耗。
背景技术
已提出TfR为受体介导的将治疗剂胞吞转送穿过血脑屏障(BBB)的靶标。虽然TfR在形成BBB的内皮细胞上表达，但TfR还在其他细胞类型上表达，包括网织红细胞。先前的工作已表明抗TfR抗体可从循环中消耗网织红细胞。
因为网织红细胞消耗由效应功能活性介导，所以可通过形成降低或消除效应功能的修饰来克服此毒性。然而，此方法阻碍想要或需要效应功能的治疗剂的使用。
因此，将效应功能阳性治疗剂递送至脑部并且不引起网织红细胞消耗的手段将为有利的。
发明内容
我们已研发被修饰以结合于TfR的Fc多肽。这些Fc多肽能够通过在BBB处结合于TfR来进行受体介导的胞吞转送而主动转运至脑中。因为Fc多肽能够通过结合于免疫细胞上的Fcγ受体(FcγR)诱导效应功能活性，包括ADCC，并且因为TfR在网织红细胞上表达，所以这些多肽同时结合于网织红细胞与FcγR可导致网织红细胞消耗。虽然可通过将突变引入Fc多肽中来降低或消除效应功能，但在一些治疗应用中这是不希望的。
本公开是基于被修饰的Fc多肽二聚体的研发，所述被修饰的Fc多肽二聚体结合TfR，穿过BBB，并且保留效应功能活性但不引起实质性TfR依赖性毒性，包括网织红细胞的消耗。可如本文所描述对此类二聚体进行工程化。
在一个方面中，本公开提供了一种被修饰的Fc多肽二聚体，或其二聚体片段，所述被修饰的Fc多肽二聚体，或其二聚体片段：(a)包含特异性结合TfR的TfR结合位点；(b)能够结合Fcγ受体(FcγR)；并且(c)不大体上消耗体内网织红细胞。
在一个方面中，本公开提供了一种被修饰的Fc多肽二聚体，或其二聚体片段，所述被修饰的Fc多肽二聚体，或其二聚体片段包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含(i)TfR结合位点以及(ii)一个或多个氨基酸修饰，所述一个或多个氨基酸修饰例如当结合于TfR时减少FcγR结合(例如但当不结合于TfR时具有有限的或不具有FcγR结合减少)；以及(b)第二Fc多肽，所述第二Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰。
在此方面的一些实施方案中，TfR结合位点包含被修饰的CH3结构域。在一些实施方案中，被修饰的CH3结构域衍生自人IgG1、IgG2、IgG3或IgG4 CH3结构域。在特定实施方案中，被修饰的CH3结构域包含在包含384、386、387、388、389、390、413、416以及421的根据EU编号的氨基酸位置集合中的五个、六个、七个、八个或九个取代。在特定实施方案中，被修饰的CH3结构域还包含在包含380、391、392以及415的位置的一个、两个、三个或四个取代。
在一些实施方案中，被修饰的CH3结构域还包含在包含414、424以及426的位置的一个、两个或三个取代。
在一些实施方案中，被修饰的Fc多肽二聚体结合于TfR的顶端结构域。在一些实施方案中，被修饰的Fc多肽二聚体结合于TfR，而不抑制转铁蛋白与TfR的结合。在特定实施方案中，被修饰的Fc多肽二聚体结合于包含TfR的氨基酸208的表位。
在一些实施方案中，被修饰的CH3结构域包含在位置388的Trp。在一些实施方案中，被修饰的CH3结构域包含在位置421的芳族氨基酸。在特定实施方案中，在位置421的芳族氨基酸为Trp或Phe。
在此方面的一些实施方案中，被修饰的CH3结构域包含至少一个选自以下的位置：位置384为Leu、Tyr、Met或Val；位置386为Leu、Thr、His或Pro；位置387为Val、Pro或酸性氨基酸；位置388为Trp；位置389为Val、Ser或Ala；位置413为Glu、Ala、Ser、Leu、Thr或Pro；位置416为Thr或酸性氨基酸；以及位置421为Trp、Tyr、His或Phe。
在此方面的一些实施方案中，被修饰的CH3结构域包含选自以下的两个、三个、四个、五个、六个、七个或八个位置：位置384为Leu、Tyr、Met或Val；位置386为Leu、Thr、His或Pro；位置387为Val、Pro或酸性氨基酸；位置388为Trp；位置389为Val、Ser或Ala；位置413为Glu、Ala、Ser、Leu、Thr或Pro；位置416为Thr或酸性氨基酸；以及位置421为Trp、Tyr、His或Phe。
在此方面的一些实施方案中，被修饰的CH3结构域包含在位置384的Leu或Met；在位置386的Leu、His或Pro；在位置387的Val；在位置388的Trp；在位置389的Val或Ala；在位置413的Pro；在位置416的Thr；和/或在位置421的Trp。
在一些实施方案中，被修饰的CH3结构域还包含在位置391的Ser、Thr、Gln或Phe。在一些实施方案中，被修饰的CH3结构域还包含在位置380的Trp、Tyr、Leu或Gln。在一些实施方案中，被修饰的CH3结构域还包含在位置392的Gln、Phe或His。在一些实施方案中，被修饰的CH3结构域还包含在位置380的Trp和/或在位置392的Gln。
在一些实施方案中，被修饰的CH3结构域还包含选自以下的一个、两个或三个位置：位置414为Lys、Arg、Gly或Pro；位置424为Ser、Thr、Glu或Lys；以及位置426为Ser、Trp或Gly。
在一些实施方案中，被修饰的CH3结构域包含在位置384的Tyr、在位置386的Thr、在位置387的Glu或Val、在位置388的Trp、在位置389的Ser、在位置413的Ser或Thr、在位置416的Glu和/或在位置421的Phe。在一些实施方案中，被修饰的CH3结构域还包含在位置380的Trp、Tyr、Leu或Gln。在一些实施方案中，被修饰的CH3结构域还包含在位置415的Glu。在一些实施方案中，被修饰的CH3结构域还包含在位置380的Trp和/或在位置415的Glu。在一些实施方案中，被修饰的CH3结构域包含在位置390的Asn。
在一些实施方案中，被修饰的CH3结构域包含以下取代中的一者或多者：在位置380的Trp；在位置386的Thr；在位置388的Trp；在位置389的Val；在位置413的Ser或Thr；在位置415的Glu；和/或在位置421的Phe。
在一些实施方案中，被修饰的CH3结构域与SEQ ID NO:4-29和64-127中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。在特定实施方案中，被修饰的CH3结构域与SEQ ID NO:66、68、94、107-109、119以及268-270中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。
在一些实施方案中，被修饰的CH3结构域与SEQ ID NO:1的氨基酸111-217具有至少85％同一性，前提条件为所述同一性百分比不包括根据EU编号的位置384、386、387、388、389、390、413、416以及421的集合。
在一些实施方案中，被修饰的CH3结构域包含SEQ ID NO:4-29和125-127中的任一者的氨基酸154-160和/或183-191。
在一些实施方案中，被修饰的CH3结构域包含至少一个选自以下的位置：位置380为Trp、Leu或Glu；位置384为Tyr或Phe；位置386为Thr；位置387为Glu；位置388为Trp；位置389为Ser、Ala、Val或Asn；位置390为Ser或Asn；位置413为Thr或Ser；位置415为Glu或Ser；位置416为Glu；以及位置421为Phe。在一些实施方案中，被修饰的CH3结构域包含选自以下的2个、3个、4个、5个、6个、7个、8个、9个、10个或11个位置：位置380为Trp、Leu或Glu；位置384为Tyr或Phe；位置386为Thr；位置387为Glu；位置388为Trp；位置389为Ser、Ala、Val或Asn；位置390为Ser或Asn；位置413为Thr或Ser；位置415为Glu或Ser；位置416为Glu；以及位置421为Phe。
在一些实施方案中，被修饰的CH3结构域包含如下11个位置：位置380为Trp、Leu或Glu；位置384为Tyr或Phe；位置386为Thr；位置387为Glu；位置388为Trp；位置389为Ser、Ala、Val或Asn；位置390为Ser或Asn；位置413为Thr或Ser；位置415为Glu或Ser；位置416为Glu；以及位置421为Phe。
在一些实施方案中，被修饰的CH3结构域与SEQ ID NO:4-29和64-127中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。在特定实施方案中，被修饰的CH3结构域与SEQ ID NO:66、68、94、107-109、119以及268-270中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。
在一些实施方案中，在对应于根据EU编号方案的位置380、384、386、384、388、389、390、391、392、413、414、415、416、421、424以及426的位置中的至少5者、6者、7者、8者、9者、10者、11者、12者、13者、14者、15者或16者处的残基未发生缺失或取代。
在一些实施方案中，被修饰的CH3结构域包含SEQ ID NO:38-61和131-173中的任一者的序列。
在此方面的一些实施方案中，被修饰的CH3结构域还包含根据EU编号方案(i)在位置366的Trp或者(ii)在位置366的Ser、在位置368的Ala以及在位置407的Val。
在此方面的一些实施方案中，对应的未修饰CH3结构域为人IgG1、IgG2、IgG3或IgG4 CH3结构域。
在此方面的一些实施方案中，例如当结合于TfR时减少FcγR结合的氨基酸修饰包含根据EU编号方案在位置234和在位置235的Ala。在一些实施方案中，例如当结合于TfR时减少FcγR结合的氨基酸修饰还包含根据EU编号方案在位置329的Gly。
在此方面的一些实施方案中，第一Fc多肽和/或第二Fc多肽包含增加血清稳定性(例如血清半衰期)的氨基酸修饰。在一些实施方案中，增加血清稳定性(例如血清半衰期)的氨基酸修饰包含根据EU编号方案在位置252的Tyr、在位置254的Thr以及在位置256的Glu。在一些实施方案中，增加血清稳定性(例如血清半衰期)的氨基酸修饰包含根据EU编号方案(i)在位置428的Leu和在位置434的Ser，或者(ii)在位置434的Ser或Ala。
在此方面的一些实施方案中，被修饰的Fc多肽二聚体进一步融合至Fab。在一些实施方案中，第一Fc多肽和/或第二Fc多肽进一步融合至Fab。
在一些实施方案中，根据EU编号方案，第一Fc多肽包含杵突变T366W并且第二Fc多肽包含臼突变T366S、L368A以及Y407V。在一些实施方案中，根据EU编号方案，第一Fc多肽包含臼突变T366S、L368A以及Y407V并且第二Fc多肽包含杵突变T366W。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:178、190、202、214、226、238、238、252、286、298以及310中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:397的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:179、191、203、215、227、239、275、287、299以及311中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:397的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:181、193、205、217、229、241、277、289、301以及313中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:397的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:323、330、337、344、351、358、365、372、379以及386中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:397的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:182、194、206、218、230、242、278、290、302以及314中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:397的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:324、331、338、345、352、359、366、373、380以及387中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:397的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:178、190、202、214、226、238、252、286、298以及310中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:400的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:178、190、202、214、226、238、252、286、298以及310中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:407的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:179、191、203、215、227、239、275、287、299以及311中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:400的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:179、191、203、215、227、239、275、287、299以及311中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:407的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:181、193、205、217、229、241、277、289、301以及313中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:400的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:323、330、337、344、351、358、365、372、379以及386中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ IDNO:407的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:182、194、206、218、230、242、278、290、302以及314中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:400的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:324、331、338、345、352、359、366、373、380以及387中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:407的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:184、196、208、220、232、244、280、292、304以及316中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQID NO:391的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:185、197、209、221、233、245、281、293、305以及317中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:391的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:187、199、211、223、235、247、283、295、307以及319中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:391的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:326、333、340、347、354、361、368、375、382以及389中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:391的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:188、200、212、224、236、248、284、296、308以及320中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:391的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:327、334、341、348、355、362、369、376、383以及390中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:391的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:184、196、208、220、232、244、280、292、304以及316中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:394的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:184、196、208、220、232、244、280、292、304以及316中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:404的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:185、197、209、221、233、245、281、293、305以及317中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:394的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:185、197、209、221、233、245、281、293、305以及317中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:404的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:187、199、211、223、235、247、283、295、307以及319中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ ID NO:394的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:326、333、340、347、354、361、368、375、382以及389中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ IDNO:404的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:188、200、212、224、236、248、284、296、308以及320中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQ IDNO:394的序列。
在另一方面中，本公开提供了一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。在一些实施方案中，第一Fc多肽包含SEQ ID NO:327、334、341、348、355、362、369、376、383以及390中的任一者的序列。在一些实施方案中，第二Fc多肽包含SEQID NO:404的序列。
在本文所描述的被修饰的Fc多肽二聚体的任何方面中，被修饰的Fc多肽二聚体不大体上消耗网织红细胞(例如循环网织红细胞)。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后消耗的网织红细胞的量小于在施用对照之后消耗的网织红细胞的量。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后消耗的网织红细胞的量小于在施用对照之后消耗的网织红细胞的量的50％、45％、40％、35％、30％、25％、20％、15％、10％、8％、5％、3％、2％或1％。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后剩余的网织红细胞的量大于在施用对照之后剩余的网织红细胞的量。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后剩余的网织红细胞的量比在施用对照之后剩余的网织红细胞的量大至少1％、5％、10％、15％、20％、25％、30％、35％、40％、45％或50％。
在本文所描述的被修饰的Fc多肽二聚体的任何方面中，被修饰的Fc多肽二聚体不大体上消耗骨髓中的网织红细胞。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后骨髓中消耗的网织红细胞的量小于在施用对照之后骨髓中消耗的网织红细胞的量。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后骨髓中消耗的网织红细胞的量小于在施用对照之后骨髓中消耗的网织红细胞的量的50％、45％、40％、35％、30％、25％、20％、15％、10％、8％、5％、3％、2％或1％。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后骨髓中剩余的网织红细胞的量大于在施用对照之后骨髓中剩余的网织红细胞的量。在一些实施方案中，在施用被修饰的Fc多肽二聚体之后骨髓中剩余的网织红细胞的量比在施用对照之后骨髓中剩余的网织红细胞的量大至少1％、5％、10％、15％、20％、25％、30％、35％、40％、45％或50％。
在一些实施方案中，对照为具有完全效应功能和/或不含减少FcγR结合的突变的对应TfR结合性Fc二聚体(即，具有与上文所描述的被修饰的Fc多肽二聚体相同的引起TfR结合的突变)。
在另一方面中，本公开提供了一种能够主动转运穿过BBB的Fc多肽二聚体-Fab融合蛋白，所述Fc多肽二聚体-Fab融合蛋白包含：(a)抗体可变区，所述抗体可变区能够结合抗原，或其抗原结合片段；以及(b)被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含(i)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点以及例如当结合于TfR时减少FcγR结合(例如但当不结合于TfR时具有有限的或不具有FcγR结合减少)的一个或多个氨基酸修饰，以及(ii)第二Fc多肽，所述第二Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰。
在此方面的一些实施方案中，例如当结合于TfR时减少FcγR结合的氨基酸修饰包含根据EU编号方案在位置234和在位置235的Ala。在特定实施方案中，例如当结合于TfR时减少FcγR结合的氨基酸修饰还包含根据EU编号方案在位置329的Gly。
在此方面的一些实施方案中，第一Fc多肽和/或第二Fc多肽包含增加血清稳定性(例如血清半衰期)的氨基酸修饰。在一些实施方案中，增加血清稳定性(例如血清半衰期)的氨基酸修饰包含根据EU编号方案在位置252的Tyr、在位置254的Thr以及在位置256的Glu。在一些实施方案中，增加血清稳定性(例如血清半衰期)的氨基酸修饰包含根据EU编号方案(i)在位置428的Leu和在位置434的Ser，或者(ii)在位置434的Ser或Ala。
在此方面的一些实施方案中，抗体可变区序列包含Fab结构域。在一些实施方案中，抗体可变区序列包含两条抗体可变区重链和两条抗体可变区轻链或它们各自的片段。
在一些实施方案中，Fc多肽或Fc多肽二聚体为岩藻糖缺陷型或非岩藻糖基化的(例如如本文所描述)。
在另一方面中，本公开提供了一种药物组合物，所述药物组合物包含本文所描述的被修饰的Fc多肽二聚体和药学上可接受的载剂。
在另一方面中，本公开提供了一种药物组合物，所述药物组合物包含本文所描述的Fc多肽二聚体-Fab融合蛋白和药学上可接受的载剂。
在另一方面中，本公开提供了一种将组合物胞吞转送穿过内皮的方法，所述方法包括使内皮与包含本文所描述的被修饰的Fc多肽二聚体的组合物接触。在一些实施方案中，内皮为BBB。
在另一方面中，本公开提供了一种将组合物胞吞转送穿过内皮的方法，所述方法包括使内皮与包含本文所描述的Fc多肽二聚体-Fab融合蛋白的组合物接触。在一些实施方案中，内皮为BBB。
附图说明
图1A和图1B为表明如下情况的图：在人TfR敲入(TfRms/hu KI)小鼠中融合至抗BACE1 Fab的TfR结合性Fc多肽二聚体不消耗血液(图1A)或骨髓(图1B)中的网织红细胞，其中TfR结合性Fc多肽二聚体在二聚体的两个Fc多肽上经过修饰具有L234A和L235A(LALA)突变(参考EU编号方案编号)以减少FcγR结合。
图2A至图2D为表明如下情况的图：在人TfR敲入(TfRms/hu KI)小鼠中融合至抗BACE1 Fab的被修饰的Fc多肽二聚体(其中TfR结合性Fc多肽二聚体具有相对于TfR结合位点呈顺式构型的LALA突变(“顺-LALA”))不消耗血液(图2A：在25mg/kg下；图2C：在50mg/kg下)或骨髓(图2B：在25mg/kg下；图2D：在50mg/kg下)中的网织红细胞，而融合至抗BACE1Fab的被类似修饰的Fc多肽二聚体(其中Fc多肽二聚体具有相对于TfR结合位点反式的LALA突变)消耗血液与骨髓中的网织红细胞。
图3A和图3B为表明如下情况的图：融合至抗BACE1 Fab的顺-LALA修饰的Fc多肽二聚体(图3A：CH3C.35.21；图3B：CH3C.35.23)以及融合至抗BACE1 Fab的在两个Fc多肽上具有LALA突变的被修饰的Fc多肽不诱导TfR介导的ADCC，而具有TfR结合位点但不具有LALA突变的hIgG1在表达内源性TfR的拉莫斯细胞(Ramos cell)上诱导ADCC。
图4为表明如下情况的图：TfR结合性Fc多肽二聚体(CH3C.35.21)对TfR介导的补体依赖性细胞毒性(CDC)活性没有影响，而抗TfR对照抗体Ab204在CHO-hTfR细胞中诱导CDC。
图5为表明如下情况的图：在原代人小胶质细胞中融合至抗BACE1 Fab的顺-LALA修饰的Fc多肽二聚体诱导类似于在野生型hIgG1情况下的TfR结合性多肽中所观察到的pSyk蛋白质水平，而融合至抗BACE1 Fab的在两个Fc多肽上具有LALA突变的被修饰的Fc多肽二聚体不诱导pSyk。
图6A和图6B为表明如下情况的图：具有顺-LALA Fc多肽二聚体和mCD20 Fab结合位点的hIgG1引发类似于抗mCD20抗体以及具有TfR结合位点和mCD20 Fab结合位点的hIgG1的ADCC(图6A)。类似地，具有顺-LALA Fc多肽二聚体和hCD20 Fab结合位点的hIgG1所引发的Fab介导的CDC达到的程度与抗hCD20以及具有TfR结合位点和hCD20 Fab结合位点的hIgG1相同(图6B)。
图7A和图7B为表明如下情况的图：具有顺-LALA Fc多肽二聚体和mCD20 Fab结合位点的hIgG1引发类似于抗mCD20抗体以及具有TfR结合位点和mCD20 Fab结合位点的hIgG1的稳健B细胞消耗(图7A和图7B)。这些结果证实顺-LALA修饰的Fc多肽二聚体保留其Fc功能并且具有Fab介导的体内效应功能。
图8A、图8B以及图8C为表明如下情况的图：用具有顺-LALA Fc多肽二聚体情况下的TfR结合位点(CH3C.35.23.4)的抗Aβ处理的小鼠引起稳健的小胶质细胞朝向Aβ斑块的募集(图8A：小胶质细胞重叠情况下的斑块面积％；图8B：针对对照IgG校正的相同数据)并且使尺寸为30-125μm2的斑块减少(图8C)。这些结果表明具有顺-LALA Fc多肽二聚体的抗Aβ保留了针对小胶质募集的稳健效应功能和类似于抗Aβ的减少一些Aβ斑块的能力。
具体实施方式
I.引言
包括TfR结合位点的被修饰的Fc多肽二聚体能够穿过BBB，并且将治疗剂转运穿过BBB。如本文所描述，这些Fc多肽二聚体如果未工程化以降低效应功能，那么也可消耗体内网织红细胞，因为网织红细胞也表达TfR。网织红细胞消耗可通过在Fc多肽二聚体的Fc多肽中引入去除效应功能的修饰，即，去除或减少Fcγ受体(FcγR)结合的修饰(例如参考EU编号方案编号为L234A和L235A(LALA)取代)而避免。然而，在当分子的Fab部分结合于其靶标(例如治疗剂靶蛋白)时需要效应功能的情况下，此方法为不利的。
本公开提供保留效应功能但不引起实质性网织红细胞消耗的被修饰的Fc多肽二聚体。这些被修饰的Fc多肽二聚体在本文中也称为“效应功能阳性的TfR结合性Fc多肽二聚体”。在一些实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体的两个Fc多肽中仅一者(而非两个Fc多肽)被修饰以降低效应功能并且结合TfR。被修饰的Fc多肽二聚体的另一Fc多肽不含TfR结合位点或降低效应功能的任何修饰，但它可含有增强效应功能的突变。两个Fc多肽中仅一者含有TfR结合位点与当结合于TfR时减少FcγR结合的修饰而另一Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰的效应功能阳性的TfR结合性Fc多肽二聚体称为具有顺式构型。如本文所描述，测试了这些具有顺式构型的被修饰的Fc多肽二聚体对网织红细胞的影响。这些实验证实，通过向形成被修饰的Fc多肽二聚体的两个多肽中的仅一者中引入TfR结合位点与当结合于TfR时减少FcγR结合的突变两者，可使TfR结合后的效应功能降低，从而在无实质性网织红细胞消耗的情况下引起TfR结合。
如本文中详细描述，使具有不同构型的被修饰的Fc多肽二聚体融合至针对治疗剂靶标(例如CD20)的Fab，以确定当Fab结合其靶标而非TfR时是否可保留效应功能(例如ADCC和CDC)。如下文详细描述，当Fc多肽二聚体融合至Fab时，在被修饰的Fc多肽二聚体中(a)例如当结合于TfR时减少FcγR结合的修饰以及(b)引起TfR结合的修饰的特定构型可产生Fc多肽二聚体-Fab融合物，所述Fc多肽二聚体-Fab融合物仍保留效应功能(例如ADCC或CDC)，但不消耗网织红细胞。此方法允许在保留效应功能的同时使用TfR介导的转运穿过BBB。
因此，本公开部分涉及被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体已被工程化以结合TfR，当结合于TfR时具有降低的效应功能(例如ADCC或CDC)，但当Fc多肽二聚体融合至治疗剂Fab并且结合于Fab的靶抗原时仍保留效应功能(例如ADCC或CDC)。
II.定义
如本文所用，除非内容另有清楚指示，否则单数形式“一个(种)(a/an)”和“所述”包括复数指示物。因此，举例来说，提到“一种多肽”可包括两种或更多种此类分子等。
如本文所用，术语“约”和“大约”，当用于修饰数值或范围中指定的量时，表明所述数值以及本领域技术人员已知的与所述值的合理偏差(例如±20％、±10％或±5％)在所叙述值的预期含义内。
如本文所用，术语“Fc多肽”是指天然存在的免疫球蛋白重链多肽的C端区，所述C端区以作为结构性结构域的Ig折叠为特征。Fc多肽含有至少包括CH2结构域和/或CH3结构域的恒定区序列并且可含有至少部分的铰链区。一般来说，Fc多肽不含可变区。
“被修饰的Fc多肽”是指与野生型免疫球蛋白重链Fc多肽序列相比具有至少一个突变，例如取代、缺失或插入，但保留天然Fc多肽的总体Ig折叠或结构的Fc多肽。
如本文所用，术语“Fc多肽二聚体”是指两个Fc多肽的二聚体。在一些实施方案中，Fc多肽二聚体能够结合Fc受体(例如FcγR)。在Fc多肽二聚体中，两个Fc多肽通过两个CH3抗体恒定域之间的相互作用发生二聚化。在一些实施方案中，两个Fc多肽还可经由两个二聚化Fc结构域单体的铰链结构域之间形成的一个或多个二硫键发生二聚化。Fc多肽二聚体可为野生型Fc多肽二聚体或被修饰的Fc多肽二聚体。野生型Fc多肽二聚体是通过两个野生型Fc多肽的二聚化而形成。Fc多肽二聚体可为异二聚体或均二聚体。
如本文所用，术语“被修饰的Fc多肽二聚体”是指含有至少一个被修饰的Fc多肽的Fc多肽二聚体。在一些实施方案中，被修饰的Fc多肽二聚体含有两个被修饰的Fc多肽。被修饰的Fc多肽二聚体可为均二聚体(即，含有两个相同的被修饰的Fc多肽)或异二聚体(即，含有两个不同的Fc多肽，其中两个Fc多肽中的至少一者为被修饰的Fc多肽)。
如本文所用的“转铁蛋白受体”或“TfR”是指转铁蛋白受体蛋白1。SEQ ID NO:63中阐述了人转铁蛋白受体1多肽序列。其他物种的转铁蛋白受体蛋白1序列也是已知的(例如黑猩猩，登录号XP_003310238.1；恒河猴，NP_001244232.1；狗，NP_001003111.1；牛，NP_001193506.1；小鼠，NP_035768.1；大鼠，NP_073203.1；以及鸡，NP_990587.1)。术语“转铁蛋白受体”还涵盖示例性参考序列(例如人序列)的对偶变体，所述对偶变体由在转铁蛋白受体蛋白1染色体基因座处的基因编码。全长TfR蛋白包括短N端细胞内区、跨膜区以及大细胞外结构域。细胞外结构域的特征为三个结构域：蛋白酶样结构域、螺旋状结构域以及顶端结构域。SEQ ID NO:31中阐述了人转铁蛋白受体1的顶端结构域序列。
如本文所用，术语“Fcγ受体”或“FcγR”是指一种类型的Fc受体，Fc受体系基于它们所识别的抗体类型来归类。FcγR包括若干成员：FcγRI(CD64)、FcγRIIA(CD32)、FcγRIIB(CD32)、FcγRIIIA(CD16a)以及FcγRIIIB(CD16b)，它们的抗体亲和力归因于不同分子结构而不同。FcγR结合于IgG类别的抗体的Fc部分并且对于诱导经调理微生物的噬菌作用为重要的。FcγR存在于免疫系统中的细胞的细胞表面。FcγR负责引发免疫系统效应功能并且在抗体的Fc部分结合至受体后活化。FcγR介导免疫功能，例如结合于附着于感染细胞或入侵病原体的抗体，从而通过抗体介导的噬菌作用或ADCC刺激吞噬细胞或细胞毒性细胞破坏微生物或感染的细胞。
如本文所用，术语“减少FcγR结合”是指被修饰的Fc多肽或被修饰的Fc多肽二聚体在被修饰的Fc多肽的CH3结构域中含有突变，其中所述突变使被修饰的Fc多肽对FcγR的亲和力与不含减少FcγR结合的突变的Fc多肽(例如野生型Fc多肽二聚体)的亲和力相比降低0.01％至90％(例如0.1％、0.5％、1％、5％、10％、15％、20％、25％、30％、35％、40％、45％、50％、55％、60％、65％、70％、75％、80％、85％或90％)。可使用例如表面等离子体共振(SPR)法(例如BiacoreTM系统)来测量FcγR结合。或者，可使用功能分析来测量FcγR结合，例如ADCC分析，诸如本文所描述的ADCC分析(例如细胞杀伤作用的体内或体外分析)。当被修饰的Fc多肽或被修饰的Fc多肽二聚体结合于TfR时可测量FcγR结合的减少。在一些实施方案中，被修饰的Fc多肽或被修饰的Fc多肽二聚体当结合于TfR时可具有减少的FcγR结合，但当不结合于TfR时具有有限的减少(例如减少不到25％、20％、15％、10％、8％、5％、3％、2％或1％)或不减少。
如本文进一步描述，被修饰的Fc多肽二聚体可含有：第一Fc多肽，所述第一Fc多肽具有TfR结合位点与当结合于TfR时减少FcγR结合的突变两者；以及第二Fc多肽，所述第二Fc多肽既不具有TfR结合位点，也不具有减少FcγR结合的突变。因此，在TfR参与后，具有第一和第二Fc多肽的所得不对称Fc多肽二聚体可具有总体降低的FcγR亲和力。相比之下，当不结合于TfR时FcγR结合可存在有限的减少(例如如上文所描述)或不减少。
术语“FcRn”是指新生儿Fc受体。Fc多肽结合于FcRn降低Fc多肽的清除率并且增加血清半衰期。人FcRn蛋白为由尺寸为约50kDa并且类似于主要组织相容性(MHC)I类蛋白的蛋白质和尺寸为约15kDa的β2-微球蛋白组成的异二聚体。
如本文所用，“FcRn结合位点”是指Fc多肽中结合于FcRn的区域。在人IgG中，如使用EU编号方案编号，FcRn结合位点包括L251、M252、I253、S254、R255、T256、M428、H433、N434、H435以及Y436。这些位置对应于位置SEQ ID NO:1的21至26、198以及203至206。
如本文所用，“天然FcRn结合位点”是指Fc多肽中结合于FcRn并且具有与天然存在的Fc多肽中结合于FcRn的区域相同的氨基酸序列的区域。
如本文所用，术语“不大体上消耗体内网织红细胞”意味着由本文所描述的效应功能阳性的TfR结合性Fc多肽二聚体或本文所描述的含有效应功能阳性的TfR结合性Fc多肽二聚体的Fc多肽二聚体-Fab融合蛋白引起的网织红细胞减少(例如骨髓网织红细胞或循环网织红细胞减少)比由对照(例如具有完全效应功能和/或不含减少FcγR结合的突变的对应TfR结合性Fc二聚体或含有具有完全效应功能和/或不含减少FcγR结合的突变的对应TfR结合性Fc二聚体的抗体)引起的网织红细胞减少(例如骨髓网织红细胞或循环网织红细胞减少)小(例如不到其80％、75％、70％、65％、60％、55％、50％、45％、40％、35％、30％、25％、20％、15％、10％、8％、5％、3％、2％或1％)。
术语“不大体上消耗体内网织红细胞”还可意味着在给予本文所描述的效应功能阳性的TfR结合性Fc多肽二聚体或本文所描述的含有效应功能阳性的TfR结合性Fc多肽二聚体的Fc多肽二聚体-Fab融合蛋白之后剩余的网织红细胞的量或百分比(例如骨髓中或循环中剩余的网织红细胞)比在给予对照(例如具有完全效应功能和/或不含减少FcγR结合的突变的对应TfR结合性Fc二聚体，或含有具有完全效应功能和/或不含减少FcγR结合的突变的对应TfR结合性Fc二聚体的抗体)之后剩余的网织红细胞(例如骨髓中或循环中剩余的网织红细胞)的量或百分比多(例如多至少1％、5％、10％、15％、20％、25％、30％、35％、40％、45％或50％)。
网织红细胞消耗(例如骨髓中或循环中的网织红细胞消耗)的量或百分比或剩余的网织红细胞(例如骨髓中或循环中剩余的网织红细胞)的量或百分比可在人TfR敲入(TfRms/hu KI)小鼠(例如人TfR顶端结构域敲入小鼠(“hTfR顶端敲入小鼠”))中测量，所述人TfR敲入小鼠经工程化以用人顶端结构域/小鼠嵌合TfR蛋白置换小鼠TfR；或在非人灵长类动物(诸如食蟹猴)中测量。如本文所描述，可通过给予被修饰的Fc二聚体或对照(例如25至50mg/kg，静脉内)(例如向TfRms/hu KI小鼠)来进行所述测量，并且可在给药后24h时使用Advia 120血液学系统通过细胞化学反应来测量循环网织红细胞。如本文所描述，可使用用于确定以下群体的FACS分选来测量骨髓网织红细胞：Ter119+、hCD71高以及FSC低群体。
如本文所用的术语“CH3结构域”和“CH2结构域”是指免疫球蛋白恒定区结构域多肽。在IgG抗体的情形中，CH3结构域多肽是指如根据EU编号方案编号的约位置341至约位置447的氨基酸区段，并且CH2结构域多肽是指如根据EU编号方案编号的约位置231至约位置340的氨基酸区段。还可根据IMGT(ImMunoGeneTics)编号方案对CH2和CH3结构域多肽进行编号，其中根据IMGT科学图表编号(IMGT网站)，CH2结构域编号为1-110并且CH3结构域编号为1-107。CH2和CH3结构域为免疫球蛋白Fc区的一部分。在IgG抗体的情形中，Fc区是指如根据EU编号方案编号的约位置231至约位置447的氨基酸区段。如本文所用，术语“Fc区”还可包括抗体铰链区的至少一部分。SEQ ID NO:62中阐述了说明性铰链区序列。
术语“可变区”是指抗体重链或轻链中衍生自生殖系可变(V)基因、多样性(D)基因或连接(J)基因(而不衍生自恒定(Cμ和Cδ)基因区段)并且给予抗体结合于抗原的特异性的结构域。典型地，抗体可变区包含穿插有三个高变“互补决定区”的四个保守“构架”区。
关于CH3或CH2结构域的术语“野生型”、“天然”以及“天然存在”在本文中用于指结构域具有自然界中存在的序列。
如本文所用，关于突变体多肽或突变体多核苷酸的术语“突变体”与“变体”可互换使用。关于给定野生型CH3或CH2结构域参考序列的变体可包括天然存在的对偶变体。“非天然”存在的CH3或CH2结构域是指在自然界中不存在于细胞中并且通过例如使用基因工程化技术或诱变技术对天然CH3结构域或CH2结构域多核苷酸或多肽进行基因修饰所产生的变体或突变体结构域。“变体”包括相对于野生型包含至少一个氨基酸突变的任何结构域。突变可包括取代、插入以及缺失。
术语“氨基酸”是指天然存在和合成的氨基酸，以及以类似于天然存在的氨基酸的方式起作用的氨基酸类似物和氨基酸模拟物。
天然存在的氨基酸为那些由遗传密码编码的氨基酸，以及随后被修饰的那些氨基酸，例如羟基脯氨酸、γ-羧基谷氨酸盐以及O-磷酸丝氨酸。“氨基酸类似物”是指具有与天然存在的氨基酸相同的基本化学结构(即结合于氢、羧基、氨基以及R基团的α碳)的化合物，例如高丝氨酸、正亮氨酸、甲硫氨酸亚砜、甲硫氨酸甲基锍。此类类似物具有被修饰的R基团(例如正亮氨酸)或被修饰的肽主链，但保留与天然存在的氨基酸相同的基本化学结构。“氨基酸模拟物”是指结构不同于氨基酸的一般化学结构，但以类似于天然存在的氨基酸的方式起作用的化合物。
天然存在的α-氨基酸包括但不限于丙氨酸(Ala)、半胱氨酸(Cys)、天冬氨酸(Asp)、谷氨酸(Glu)、苯丙氨酸(Phe)、甘氨酸(Gly)、组氨酸(His)、异亮氨酸(Ile)、精氨酸(Arg)、赖氨酸(Lys)、亮氨酸(Leu)、甲硫氨酸(Met)、天冬酰胺(Asn)、脯氨酸(Pro)、谷氨酰胺(Gln)、丝氨酸(Ser)、苏氨酸(Thr)、缬氨酸(Val)、色氨酸(Trp)、酪氨酸(Tyr)以及它们的组合。天然存在的α-氨基酸的立体异构体包括但不限于D-丙氨酸(D-Ala)、D-半胱氨酸(D-Cys)、D-天冬氨酸(D-Asp)、D-谷氨酸(D-Glu)、D-苯丙氨酸(D-Phe)、D-组氨酸(D-His)、D-异亮氨酸(D-Ile)、D-精氨酸(D-Arg)、D-赖氨酸(D-Lys)、D-亮氨酸(D-Leu)、D-甲硫氨酸(D-Met)、D-天冬酰胺(D-Asn)、D-脯氨酸(D-Pro)、D-谷氨酰胺(D-Gln)、D-丝氨酸(D-Ser)、D-苏氨酸(D-Thr)、D-缬氨酸(D-Val)、D-色氨酸(D-Trp)、D-酪氨酸(D-Tyr)以及它们的组合。
在本文中可通过通常已知的三字母符号或通过IUPAC-IUB生物化学命名委员会(IUPAC-IUB Biochemical Nomenclature Commission)建议的一字母符号提到氨基酸。
术语“多肽”和“肽”在本文中可互换地用于指单一链中的氨基酸残基的聚合物。所述术语适用于一个或多个氨基酸残基为对应天然存在的氨基酸的人工化学模拟物的氨基酸聚合物，以及天然存在的氨基酸聚合物和非天然存在的氨基酸聚合物。氨基酸聚合物可包含完全L-氨基酸、完全D-氨基酸或L与D氨基酸的混合物。
如本文所用的术语“蛋白质”是指多肽或单链多肽的二聚体(即，两者)或多聚体(即，三者或更多者)。蛋白质的单链多肽可通过共价键(例如二硫键)或非共价相互作用而连接。
术语“保守取代”、“保守突变”或“保守修饰的变体”是指使得氨基酸可归类为具有类似特征的另一氨基酸取代的改变。以此方式定义的保守氨基酸组类别的实例可包括：“带电荷/极性组”，包括Glu(谷氨酸或E)、Asp(天冬氨酸或D)、Asn(天冬酰胺或N)、Gln(谷氨酰胺或Q)、Lys(赖氨酸或K)、Arg(精氨酸或R)以及His(组氨酸或H)；“芳族组”，包括Phe(苯丙氨酸或F)、Tyr(酪氨酸或Y)、Trp(色氨酸或W)以及(组氨酸或H)；以及“脂族组”，包括Gly(甘氨酸或G)、Ala(丙氨酸或A)、Val(缬氨酸或V)、Leu(亮氨酸或L)、Ile(异亮氨酸或I)、Met(甲硫氨酸或M)、Ser(丝氨酸或S)、Thr(苏氨酸或T)以及Cys(半胱氨酸或C)。在每个组内，还可鉴定出亚组。举例来说，带电荷或极性氨基酸组可再划分成包括以下的亚组：“带正电荷的亚组”，包含Lys、Arg以及His；“带负电荷的亚组”，包含Glu和Asp；以及“极性亚组”，包含Asn和Gln。在另一实例中，芳族或环状组可再划分成包括以下的亚组：“氮环亚组”，包含Pro、His以及Trp；以及“苯基亚组”，包含Phe和Tyr。在另一实例中，脂族组可再划分成例如以下的亚组：“脂族非极性亚组”，包含Val、Leu、Gly以及Ala；以及“脂族略带极性的亚组”，包含Met、Ser、Thr以及Cys。保守突变类别的实例包括以上亚组内氨基酸的氨基酸取代，诸如但不限于：Lys取代Arg或反之亦然，使得正电荷可维持；Glu取代Asp或反之亦然，使得负电荷可维持；Ser取代Thr或反之亦然，使得游离-OH可维持；以及Gln取代Asn或反之亦然，使得游离-NH2可维持。在一些实施方案中，疏水性氨基酸取代例如活性位点中的天然存在的疏水性氨基酸以保留疏水性。
在两个或更多个多肽序列的背景下，术语“一致”或“同一性”百分比是指如使用一种序列比较算法或通过手动比对和视觉检查所测量，当在比较窗或指定区域上比较和比对以获得最大对应性时，两个或更多个序列或子序列相同或具有指定百分比的在指定区域上一致的氨基酸残基，例如至少60％、至少65％、至少70％、至少75％、至少80％、至少85％、至少90％或至少95％或更大的同一性。
对于多肽的序列比较，典型地一个氨基酸序列充当与候选序列相比较的参考序列。可使用本领域技术人员可获得的各种方法(例如视觉比对)或使用公共可获得的软件使用已知算法以实现最佳比对来进行比对。此类程序包括BLAST程序、ALIGN、ALIGN-2(Genentech,South San Francisco,Calif.)或Megalign(DNASTAR)。用于比对以实现最佳比对的参数可由本领域技术人员确定。对于用于本申请的目的的多肽序列的序列比较，使用用于比对两个蛋白质序列的BLASTP算法标准蛋白质BLAST，并且使用默认参数。
当在鉴定多肽序列中的给定氨基酸残基的背景中使用术语“对应于”、“参考……确定”或“参考……编号”时，是指当将给定氨基酸序列与参考序列最佳比对和比较时指定参考序列的残基位置。因此，举例来说，当将多肽中的氨基酸残基在与SEQ ID NO:1最佳比对时与SEQ ID NO:1中的氨基酸对齐时，所述残基“对应于”SEQ ID NO:1的区域中的氨基酸。与参考序列比对的多肽不需要与参考序列长度相同。
如本文所用，当提到如本文所描述包含被修饰的CH3结构域的多肽时，术语“特异性结合”或“选择性结合”于靶标(例如TfR或FcγR)是指使多肽与它结合于结构上不同靶标相比以更大亲和力、更大亲合力和/或更长持续时间结合于靶标的结合反应。在典型实施方案中，当在相同亲和力分析条件下分析时，多肽对特定靶标(例如TfR或FcγR)具有与不相关靶标相比至少5倍、6倍、7倍、8倍、9倍、10倍、20倍、25倍、50倍、100倍、1,000倍、10,000倍或更大的亲和力。如本文所用，术语“特异性结合特定靶标(例如TfR或FcγR)”、“特异性结合于特定靶标(例如TfR或FcγR)”或“对特定靶标(例如TfR或FcγR)具特异性”可为例如由对所结合的靶标的平衡解离常数KD为例如10-4M或更小(例如10-5M、10-6M、10-7M、10-8M、10- 9M、10-10M、10-11M或10-12M)的分子展现。在一些实施方案中，被修饰的CH3结构域多肽特异性结合于TfR上在物种间保守(例如在物种间在结构上保守)(例如在非人灵长类动物与人物种之间保守(例如在非人灵长类动物与人物种之间在结构上保守))的表位。在一些实施方案中，多肽可排他地结合于人TfR。
如本文所用的术语“结合亲和力”是指两个分子(例如多肽上的单一结合位点与它所结合的靶标(例如TfR))之间的非共价相互作用的强度。因此，举例来说，除非另外指出或由上下文来看为清楚的，否则所述术语可指多肽与其靶标之间的1:1相互作用。结合亲和力可通过测量平衡解离常数(KD)来定量，平衡解离常数是指解离速率常数(kd，时间-1)除以缔合速率常数(ka，时间-1M-1)。可通过测量复合物形成和解离的动力学来测定KD，例如使用表面等离子体共振(SPR)法，例如BiacoreTM系统；动力学排除分析，诸如
以及BioLayer干涉术(例如使用
平台)。如本文所用，“结合亲和力”不仅包括形式结合亲和力，诸如反映多肽与其靶标之间的1:1相互作用的那些形式结合亲和力，而且包括可反映亲合结合的计算KD’要获得的表观亲和力。
III.TfR结合性Fc多肽
本部分描述结合于TfR并且能够转运穿过血脑屏障(BBB)的被修饰的Fc多肽的产生。
CH3 TfR结合性多肽
在一些实施方案中，被修饰的Fc多肽含有被修饰的人Ig CH3结构域，诸如IgG CH3结构域。CH3结构域可属于任何IgG亚型，即，来自IgG1、IgG2、IgG3或IgG4。在IgG抗体的情形中，CH3结构域是指如根据EU编号方案编号的约位置341至约位置447的氨基酸区段。除非另外指明，否则CH3结构域中用于鉴定用于TfR结合的对应氨基酸位置集合的目的的位置是参考EU编号方案、SEQ ID NO:3或SEQ ID NO:1的氨基酸111-217来确定。取代也是参考EU编号方案或SEQ ID NO:1来确定，即，将氨基酸视为相对于EU编号方案或SEQ ID NO:1中的对应氨基酸位置的取代。
如上文所指出，CH3结构域中可被修饰的残基的集合在本文中是参考EU编号方案或SEQ ID NO:1来编号。任何CH3结构域(例如IgG1、IgG2、IgG3或IgG4 CH3结构域)均可在对应于EU编号方案或SEQ ID NO:1中所指出位置的残基的一个或多个残基集合中具有修饰，例如氨基酸取代。IgG1、IgG2、IgG3以及IgG4序列中的每一者中对应于EU编号方案或SEQ IDNO:1的任何给定位置的位置可容易地确定。
本领域技术人员理解其他免疫球蛋白同型(例如IgM、IgA、IgE、IgD等)的CH3结构域可通过鉴定那些结构域中对应于本文所描述的氨基酸位置的氨基酸来进行类似修饰。还可对其他物种(例如非人灵长类动物、猴、小鼠、大鼠、兔、狗、猪、鸡等)的免疫球蛋白的对应结构域进行修饰。
在一个实施方案中，特异性结合TfR的被修饰的CH3结构域多肽在包含全长人TfR序列(SEQ ID NO:63)的位置208的表位处结合于TfR的顶端结构域，所述位置对应于SEQ IDNO:31中所阐述的人TfR顶端结构域序列的位置11。SEQ ID NO:31对应于人TfR-1统一蛋白质(uniprotein)序列P02786(SEQ ID NO:63)的氨基酸198-378。在一些实施方案中，被修饰的CH3结构域多肽在包含全长人TfR序列(SEQ ID NO:63)的位置158、188、199、207、208、209、210、211、212、213、214、215和/或294的表位处结合于TfR的顶端结构域。被修饰的CH3结构域多肽可结合于TfR，而不阻断或以其他方式抑制转铁蛋白与受体的结合。在一些实施方案中，转铁蛋白与TfR的结合不大体上受抑制。在一些实施方案中，转铁蛋白与TfR的结合被抑制不到约50％(例如不到约45％、40％、35％、30％、25％、20％、15％、10％或5％)。在一些实施方案中，转铁蛋白与TfR的结合被抑制不到约20％(例如不到约19％、18％、17％、16％、15％、14％、13％、12％、11％、10％、9％、8％、7％、6％、5％、4％、3％、2％或1％)。展现此结合特异性的说明性CH3结构域多肽包括根据EU编号方案在位置380、384、386、387、388、389、390、413、415、416以及421具有氨基酸取代的多肽。
CH3 TfR结合集合：384、386、387、388、389、390、413、416以及421
在一些实施方案中，被修饰的CH3结构域多肽包含在包含根据EU编号方案的380、384、386、387、388、389、390、413、415、416以及421的氨基酸位置的集合(集合CH3C)中的一个、两个、三个、四个、五个、六个、七个、八个、九个、十个或十一个取代。表3中示出了可在这些位置引入的说明性取代。表4中示出了额外的取代。在一些实施方案中，在位置388和/或421的氨基酸为芳族氨基酸，例如Trp、Phe或Tyr。在一些实施方案中，在位置388的氨基酸为Trp。在一些实施方案中，在位置388的氨基酸为Gly。在一些实施方案中，在位置421的芳族氨基酸为Trp或Phe。
在某些实施方案中，被修饰的CH3结构域多肽包含选自以下的一个、两个、三个、四个、五个、六个、七个、八个、九个、十个或十一个位置：在位置380的Glu、Leu、Ser、Val、Trp、Tyr或Gln；在位置384的Leu、Tyr、Phe、Trp、Met、Pro或Val；在位置386的Leu、Thr、His、Pro、Asn、Val或Phe；在位置387的Val、Pro、Ile或酸性氨基酸；在位置388的Trp；在位置389的脂族氨基酸、Gly、Ser、Thr或Asn；在位置390的Gly、His、Gln、Leu、Lys、Val、Phe、Ser、Ala、Asp、Glu、Asn、Arg或Thr；在位置413的酸性氨基酸、Ala、Ser、Leu、Thr、Pro、Ile或His；在位置415的Glu、Ser、Asp、Gly、Thr、Pro、Gln或Arg；在位置416的Thr、Arg、Asn或酸性氨基酸；和/或在位置421的芳族氨基酸、His或Lys。
在一些实施方案中，特异性结合于TfR的被修饰的CH3结构域多肽包含如下至少一个具有取代的位置(根据EU编号方案)：在位置384的Leu、Tyr、Met或Val；在位置386的Leu、Thr、His或Pro；在位置387的Val、Pro或酸性氨基酸；在位置388的芳族氨基酸(例如Trp或Gly)(例如Trp)；在位置389的Val、Ser或Ala；在位置413的酸性氨基酸、Ala、Ser、Leu、Thr或Pro；在位置416的Thr或酸性氨基酸；或者在位置421的Trp、Tyr、His或Phe。在一些实施方案中，被修饰的CH3结构域多肽可包含保守取代，例如集合中的一个或多个位置处的指定氨基酸的相同电荷分组、疏水性分组、侧链环结构分组(例如芳族氨基酸)或尺寸分组和/或极性或非极性分组中的氨基酸。因此，举例来说，Ile可存在于位置384、386和/或位置413。在一些实施方案中，在位置387、413以及416中的一者、两者或每一者的位置的酸性氨基酸为Glu。在其他实施方案中，在位置387、413以及416中的一者、两者或每一者处的酸性氨基酸为Asp。在一些实施方案中，位置384、386、387、388、389、413、416以及421中的两者、三者、四者、五者、六者、七者或所有八者处具有如此段落中所指定的氨基酸取代。
在一些实施方案中，具有集合CH3C中的修饰的CH3结构域多肽包含在位置390的天然Asn。在一些实施方案中，被修饰的CH3结构域多肽包含在位置390的Gly、His、Gln、Leu、Lys、Val、Phe、Ser、Ala或Asp。在一些实施方案中，被修饰的CH3结构域多肽在包含380、391、392以及415的位置还包含一个、两个、三个或四个取代。在一些实施方案中，Trp、Tyr、Leu或Gln可存在于位置380。在一些实施方案中，Ser、Thr、Gln或Phe可存在于位置391。在一些实施方案中，Gln、Phe或His可存在于位置392。在一些实施方案中，Glu可存在于位置415。
在某些实施方案中，被修饰的CH3结构域多肽包含选自以下的两个、三个、四个、五个、六个、七个、八个、九个或十个位置：在位置380的Trp、Leu或Glu；在位置384的Tyr或Phe；在位置386的Thr；在位置387的Glu；在位置388的Trp；在位置389的Ser、Ala、Val或Asn；在位置390的Ser或Asn；在位置413的Thr或Ser；在位置415的Glu或Ser；在位置416的Glu；和/或在位置421的Phe。在一些实施方案中，被修饰的CH3结构域多肽包含如下所有十一个位置：在位置380的Trp、Leu或Glu；在位置384的Tyr或Phe；在位置386的Thr；在位置387的Glu；在位置388的Trp；在位置389的Ser、Ala、Val或Asn；在位置390的Ser或Asn；在位置413的Thr或Ser；在位置415的Glu或Ser；在位置416的Glu；和/或在位置421的Phe。
在某些实施方案中，被修饰的CH3结构域多肽包含在位置384的Leu或Met；在位置386的Leu、His或Pro；在位置387的Val；在位置388的Trp；在位置389的Val或Ala；在位置413的Pro；在位置416的Thr；和/或在位置421的Trp。在一些实施方案中，被修饰的CH3结构域多肽还包含在位置391的Ser、Thr、Gln或Phe。在一些实施方案中，被修饰的CH3结构域多肽还包含在位置380的Trp、Tyr、Leu或Gln和/或在位置392的Gln、Phe或His。在一些实施方案中，Trp存在于位置380和/或Gln存在于位置392。在一些实施方案中，被修饰的CH3结构域多肽不具有在位置380的Trp。
在其他实施方案中，被修饰的CH3结构域多肽包含在位置384的Tyr；在位置386的Thr；在位置387的Glu或Val；在位置388的Trp；在位置389的Ser；在位置413的Ser或Thr；在位置416的Glu；和/或在位置421的Phe。在一些实施方案中，被修饰的CH3结构域多肽包含在位置390的天然Asn。在某些实施方案中，被修饰的CH3结构域多肽还包含在位置380的Trp、Tyr、Leu或Gln；和/或在位置415的Glu。在一些实施方案中，被修饰的CH3结构域多肽还包含在位置380的Trp和/或在位置415的Glu。
在其他实施方案中，被修饰的CH3结构域还包含选自以下的一个、两个或三个位置：位置414为Lys、Arg、Gly或Pro；位置424为Ser、Thr、Glu或Lys；以及位置426为Ser、Trp或Gly。
在一些实施方案中，被修饰的CH3结构域包含以下取代中的一者或多者：在位置380的Trp；在位置386的Thr；在位置388的Trp；在位置389的Val；在位置413的Ser或Thr；在位置415的Glu；和/或在位置421的Phe。
在一些实施方案中，特异性结合TfR的被修饰的CH3结构域多肽与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸111-217具有至少70％同一性、至少75％同一性、至少80％同一性、至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，此类被修饰的CH3结构域多肽包含SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸154-160和/或183-191。在一些实施方案中，此类被修饰的CH3结构域多肽包含SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸150-160和/或183-191。在一些实施方案中，被修饰的CH3结构域多肽包含SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸150-160和/或183-196。
在一些实施方案中，被修饰的CH3结构域多肽与SEQ ID NO:1的氨基酸111-217具有至少70％同一性、至少75％同一性、至少80％同一性、至少85％同一性、至少90％同一性或至少95％同一性，前提条件为所述同一性百分比不包括SEQ ID NO:1的位置154、156、157、158、159、160、183、186以及191(根据EU编号方案，位置384、386、387、388、389、390、413、416以及421)的集合。在一些实施方案中，被修饰的CH3结构域多肽包含如SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者中所阐述的氨基酸154-160和/或氨基酸183-191。
在一些实施方案中，被修饰的CH3结构域多肽与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者具有至少70％同一性、至少75％同一性、至少80％同一性、至少85％同一性、至少90％同一性或至少95％同一性，前提条件为对应于SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的位置150、154、156、157、158、159、160、161、162、183、184、185、186、191、194以及196(根据EU编号方案，位置380、384、386、384、388、389、390、391、392、413、414、415、416、421、424以及426)的位置中的至少五者、六者、七者、八者、九者、十者、十一者、十二者、十三者、十四者、十五者或十六者未发生缺失或取代。
在一些实施方案中，被修饰的CH3结构域多肽与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者具有至少75％同一性、至少80％同一性、至少85％同一性、至少90％同一性或至少95％同一性并且还包含如下位置中的至少五者、六者、七者、八者、九者、十者、十一者、十二者、十三者、十四者、十五者或十六者：在位置380的Trp、Tyr、Leu、Gln或Glu；在位置384的Leu、Tyr、Met或Val；在位置386的Leu、Thr、His或Pro；在位置387的Val、Pro或酸性氨基酸；在位置388的芳族氨基酸(例如Trp)；在位置389的Val、Ser或Ala；在位置390的Ser或Asn；在位置391的Ser、Thr、Gln或Phe；在位置392的Gln、Phe或His；在位置413的酸性氨基酸、Ala、Ser、Leu、Thr或Pro；在位置414的Lys、Arg、Gly或Pro；在位置415的Glu或Ser；在位置416的Thr或酸性氨基酸；在位置421的Trp、Tyr、His或Phe；在位置424的Ser、Thr、Glu或Lys；以及在位置426的Ser、Trp或Gly。
在一些实施方案中，TfR结合性多肽包含SEQ ID NO:38-52中的任一者的氨基酸序列。在其他实施方案中，TfR结合性多肽包含SEQ ID NO:38-52中的任一者的氨基酸序列，但其中一个或两个氨基酸被取代。在一些实施方案中，多肽包含SEQ ID NO:38-52中的任一者的氨基酸序列，但其中三个氨基酸被取代。
在一些实施方案中，TfR结合性多肽包含SEQ ID NO:53-61中的任一者的氨基酸序列。在其他实施方案中，TfR结合性多肽包含SEQ ID NO:53-61中的任一者的氨基酸序列，但其中一个或两个氨基酸被取代。在一些实施方案中，多肽包含SEQ ID NO:53-61中的任一者的氨基酸序列，但其中三个或四个氨基酸被取代。
在一些实施方案中，TfR结合性多肽包含SEQ ID NO:131-167中的任一者的氨基酸序列。在其他实施方案中，TfR结合性多肽包含SEQ ID NO:131-167中的任一者的氨基酸序列，但其中一个或两个氨基酸被取代。在一些实施方案中，多肽包含SEQ ID NO:131-167中的任一者的氨基酸序列，但其中三个氨基酸被取代。
在一些实施方案中，TfR结合性多肽包含SEQ ID NO:58、60以及168-173中的任一者的氨基酸序列。在其他实施方案中，TfR结合性多肽包含SEQ ID NO:58、60以及168-173中的任一者的氨基酸序列，但其中一个或两个氨基酸被取代。在一些实施方案中，多肽包含SEQ ID NO:58、60以及168-173中的任一者的氨基酸序列，但其中三个或四个氨基酸被取代。
在其他实施方案中，TfR结合性多肽包含SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸157-194、氨基酸153-194或氨基酸153-199。在其他实施方案中，多肽包含与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸157-194，或与氨基酸153-194，或与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的氨基酸153-199具有至少75％同一性、至少80％同一性、至少85％同一性、至少90％同一性或至少95％同一性的氨基酸序列。
在一些实施方案中，多肽包含SEQ ID NO:4-29、64-127以及268-274(例如SEQ IDNO:66、68、94、107-109、119以及268-270)中的任一者。在其他实施方案中，多肽可与SEQ IDNO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者具有至少75％同一性、至少80％同一性、至少85％同一性、至少90％同一性或至少95％同一性。
FcRn结合位点
本文所描述的可转运穿过BBB的多肽另外可包含FcRn结合位点。在一些实施方案中，FcRn结合位点在被修饰的Fc多肽或其片段内。
在一些实施方案中，FcRn结合位点包含天然FcRn结合位点。在一些实施方案中，FcRn结合位点相对于天然FcRn结合位点的氨基酸序列不包含氨基酸变化。在一些实施方案中，天然FcRn结合位点为IgG结合位点，例如人IgG结合位点。在一些实施方案中，FcRn结合位点包含改变FcRn结合的修饰。
在一些实施方案中，FcRn结合位点具有发生突变(例如取代)的一个或多个氨基酸残基，其中所述一个或多个突变增加血清半衰期或不大体上减少血清半衰期(即，当在相同条件下分析时与在突变位置具有野生型残基的对应蛋白质相比使血清半衰期缩减不超过25％)。在一些实施方案中，FcRn结合位点在位置21至26、198以及203至206具有发生取代的一个或多个氨基酸残基，其中所述位置是参考SEQ ID NO:1确定。
在一些实施方案中，FcRn结合位点相对于天然人IgG序列包含一个或多个突变，所述一个或多个突变延长被修饰的多肽的血清半衰期。在一些实施方案中，在如参考SEQ IDNO:1确定的位置14-27、49-54、77-87、153-160以及198-205(所述位置对应于使用EU编号的位置244-257、279-284、307-317、383-390以及428-435)中的一者或多者处引入突变(例如取代)。在一些实施方案中，在如参考SEQ ID NO:1确定的位置21、22、24、25、26、77、78、79、81、82、84、155、156、157、159、198、203、204或206(所述位置对应于使用EU编号的位置251、252、254、255、256、307、308、309、311、312、314、385、386、387、389、428、433、434或436)处引入一个或多个突变。在一些实施方案中，将突变引入如参考SEQ ID NO:1确定的位置22、24以及25(所述位置对应于使用EU编号的位置252、254以及256)中的一者、两者或三者中。在一些实施方案中，突变为如参考SEQ ID NO:1编号的M22Y、S24T以及T26E。在一些实施方案中，本文所描述的被修饰的Fc多肽还包含突变M22Y、S24T以及T26E。在一些实施方案中，将突变引入如参考SEQ ID NO:1确定的位置198和204(所述位置对应于使用EU编号的位置428和434)中的一者或两者中。在一些实施方案中，突变为如参考SEQ ID NO:1编号的M198L和N204S。在一些实施方案中，本文所描述的被修饰的Fc多肽还包含突变N204S加上或不加上M198L。在一些实施方案中，被修饰的Fc多肽包含在根据EU编号的位置T307、E380以及N434(所述位置对应于如参考SEQ ID NO:1编号的T77、E150以及N204)中的一者、两者或所有三者处的取代。在一些实施方案中，突变为T307Q和N434A(SEQ ID NO:1，T77Q和N204A)。在一些实施方案中，被修饰的Fc多肽包含突变T307A、E380A以及N434A(SEQ ID NO:1，T77A、E150A以及N204A)。在一些实施方案中，被修饰的Fc多肽包含在位置T250和M428(所述位置对应于如参考SEQ ID NO:1编号的T20和M198)的取代。在一些实施方案中，Fc多肽包含突变T250Q和/或M428L(SEQ ID NO:1，T20Q和M198L)。在一些实施方案中，被修饰的Fc多肽包含在位置M428和N434(所述位置对应于如参考SEQ ID NO:1编号的M198和N204)的取代。在一些实施方案中，被修饰的Fc多肽包含取代M428L和N434S(所述位置对应于如参考SEQ IDNO:1编号的M198L和N204S)。在一些实施方案中，被修饰的Fc多肽包含N434S或N434A取代(所述取代对应于如参考SEQ ID NO:1编号的N204S或N204A)。
IV.降低效应功能或减少FcγR结合的突变
如本文所提供的被修饰以结合TfR并且起始转运穿过BBB的Fc多肽还可包含额外的突变以降低效应功能。如本文所描述，通过将TfR结合位点与减少FcγR结合的突变两者引入Fc多肽二聚体的同一Fc多肽中，可使TfR结合后的效应功能降低，从而在无实质性网织红细胞消耗的情况下引起TfR结合，但当Fc多肽二聚体融合至治疗剂Fab并且结合于Fab的靶抗原时仍保留效应功能(例如ADCC或CDC)。
在一些实施方案中，包含被修饰的CH3结构域的Fc多肽具有效应功能，即，在结合于在介导效应功能的效应细胞上所表达的Fc受体后诱导某些生物功能的能力。效应细胞包括但不限于单核细胞、巨噬细胞、嗜中性粒细胞、树突细胞、嗜酸性粒细胞、肥大细胞、血小板、B细胞、大颗粒淋巴细胞、郎格汉斯细胞(Langerhans'cell)、自然杀手(NK)细胞以及细胞毒性T细胞。
效应功能的实例包括但不限于C1q结合和CDC、Fc受体结合、ADCC、抗体依赖性细胞介导的噬菌作用(ADCP)、细胞表面受体(例如B细胞受体)的下调以及B细胞活化。效应功能可随抗体类别而变化。举例来说，天然人IgG1和IgG3抗体可在结合于免疫系统细胞上存在的适当Fc受体后引发ADCC和CDC活性；并且天然人IgG1、IgG2、IgG3以及IgG4可在结合于免疫细胞上存在的适当Fc受体后引发ADCP功能。
在一些实施例中，如本文所描述具有TfR结合位点的Fc多肽可包括降低效应功能(即，使TfR结合后的效应功能降低)的额外修饰。Fc多肽二聚体在TfR结合后具有降低的效应功能为希望的，因为这使得因网织红细胞在细胞表面上也具有TfR而引起的网织红细胞消耗降低。如本文中详细描述，具有顺式构型的Fc多肽二聚体(即，在Fc多肽二聚体的同一Fc多肽上具有TfR结合位点与降低效应功能的突变两者的Fc多肽二聚体)在无实质性网织红细胞消耗的情况下展现TfR结合，但当Fc多肽二聚体融合至治疗剂Fab并且结合于Fab的靶抗原时仍保留效应功能(例如ADCC或CDC)。当Fc多肽二聚体融合至结合于Fab的靶抗原的治疗剂Fab时具有效应功能为例如癌症治疗剂(例如脑癌治疗剂)中希望的。
调节效应功能的说明性Fc多肽突变包括但不限于CH2结构域中例如在对应于SEQID NO:1的位置4和5(根据EU编号方案的位置234和235)的位置的取代。在一些实施方案中，被修饰的CH2结构域中的取代包含在SEQ ID NO:1的位置4和5的Ala。在一些实施方案中，被修饰的CH2结构域中的取代包含在SEQ ID NO:1的位置4和5的Ala以及在位置99的Gly。
调节效应功能的额外Fc多肽突变包括但不限于在位置238、265、269、270、297、327以及329(EU编号方案，所述位置对应于如参考SEQ ID NO:1编号的位置8、35、39、40、67、97以及99)的一个或多个取代。说明性取代(如用EU编号方案编号)包括以下情况：位置329可具有如下突变，其中脯氨酸用甘氨酸或精氨酸或足够大以破坏在Fc的脯氨酸329与FcγRIII的色氨酸残基Trp 87和Trp 110之间形成的Fc/Fcγ受体界面的氨基酸残基取代。额外的说明性取代包括S228P、E233P、L235E、N297A、N297D以及P331S。还可存在多重取代，例如人IgG1 Fc区的L234A和L235A；人IgG1 Fc区的L234A、L235A以及P329G；人IgG4 Fc区的S228P和L235E；人IgG1 Fc区的L234A和G237A；人IgG1 Fc区的L234A、L235A以及G237A；人IgG2 Fc区的V234A和G237A；人IgG4 Fc区的L235A、G237A以及E318A；以及人IgG4 Fc区的S228P和L236E。在一些实施方案中，Fc多肽可具有调节ADCC的一个或多个氨基酸取代，例如根据EU编号方案在Fc区的位置298、333和/或334的取代。
在一些实施方案中，如本文所描述的多肽可具有增加或减小ADCC的一个或多个氨基酸取代或可具有改变C1q结合和/或CDC的突变。
在特定实施方案中，可对具有TfR结合位点的Fc多肽进行修饰以降低效应功能，即，减少FcγR结合。在一些实施方案中，具有TfR结合位点的Fc多肽可包括突变L234A和L235A(EU编号方案，它们对应于如参考SEQ ID NO:1编号的位置4和5)。在其他实施方案中，具有TfR结合位点的Fc多肽可包括突变L234A、L235A以及P329G(EU编号方案，它们对应于如参考SEQ ID NO:1编号的位置4、5以及99)。
V.效应功能阳性的TfR结合性Fc多肽二聚体
在某些方面中，本公开提供效应功能阳性的TfR结合性Fc多肽二聚体，所述效应功能阳性的TfR结合性Fc多肽二聚体被修饰以结合于TfR并且当结合于TfR时具有减少的FcγR结合，但当不结合于TfR时具有有限的或不具有FcγR结合减少。这些被修饰的Fc多肽二聚体可融合至治疗剂Fab以将其转运穿过BBB。这些被修饰的Fc多肽二聚体被证实在TfR结合后具有降低的效应功能。当被修饰的Fc多肽二聚体融合至Fab时，当Fab结合于其靶标(例如癌细胞上的靶标)时Fc多肽二聚体保留效应功能。以此方式，本文所描述的效应功能阳性的TfR结合性Fc多肽二聚体能够在无实质性网织红细胞(网织红细胞也在细胞表面上含有TfR)消耗的情况下将Fab转运穿过BBB，并且通过展现可在Fab结合于其靶标时靶向细胞外聚集物(例如斑块)或脑中的某些患病细胞(例如癌细胞)进行破坏的效应功能也服务于其治疗目的。
本文所描述的效应功能阳性的TfR结合性Fc多肽二聚体具有顺式构型，这意味着在Fc多肽二聚体中仅一个(并非两个)Fc多肽被修饰以具有TfR结合位点以及当结合于TfR时减少FcγR结合的修饰。Fc多肽二聚体中的另一Fc多肽不含TfR结合位点或大体上减少FcγR结合的修饰。被修饰的Fc多肽二聚体的反式构型是指Fc多肽二聚体中两个Fc多肽中的一者含有TfR结合位点，而另一Fc多肽含有例如当结合于TfR时减少FcγR结合的修饰。如本文所证实，具有顺式构型而非反式构型的被修饰的Fc多肽二聚体能够降低血液和骨髓中的网织红细胞消耗(参见例如图2A至图2D)。
在一个实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点以及根据EU编号方案的氨基酸修饰L234A和L235A，以及(b)第二Fc多肽，所述第二Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含氨基酸修饰N434S加上或不加上M428L并且不含TfR结合位点或减少FcγR结合的任何修饰。
在一个实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及杵突变T366W，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；杵突变T366W；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；以及臼突变T366S、L368A以及Y407V，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰M252Y、S254T以及T256E，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰M252Y、S254T以及T256E，并且不含TfR结合位点或减少FcγR结合的任何修饰。
在另一实施方案中，效应功能阳性的TfR结合性Fc多肽二聚体包含：(a)第一Fc多肽，所述第一Fc多肽包含特异性结合TfR的TfR结合位点；根据EU编号方案的氨基酸修饰L234A、L235A以及P329G；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
VI.测量效应功能或FcγR结合
用于分析Fc多肽二聚体与FcγR之间的结合亲和力、结合动力学以及交叉反应性的方法为本领域中已知的。这些方法包括但不限于固相结合分析(例如ELISA分析)、免疫沉淀、表面等离子体共振(例如BiacoreTM(GE Healthcare,Piscataway,NJ))、动力学排除分析(例如
)、流式细胞术、荧光激活细胞分选(FACS)、BioLayer干涉术(例如
(FortéBio,Inc.,Menlo Park,CA))以及西方墨点分析(Western blot analysis)。在一些实施方案中，使用ELISA来测定结合亲和力和/或交叉反应性。用于进行ELISA分析的方法为本领域中已知的。在一些实施方案中，使用表面等离子体共振(SPR)来测定结合亲和力、结合动力学和/或交叉反应性。在一些实施方案中，使用动力学排除分析来测定结合亲和力、结合动力学和/或交叉反应性。在一些实施方案中，使用BioLayer干涉术分析来测定结合亲和力、结合动力学和/或交叉反应性。
ADCC为一种类型的免疫反应，其中抗体结合于病原或致瘤靶细胞表面的抗原并且通过效应细胞(例如外周血单核细胞，例如自然杀手(NK)细胞、T细胞以及B细胞)对其进行鉴定以便进行破坏。带有FcγR的效应细胞识别并且结合与靶细胞结合的抗体的Fc区。抗体因此赋予靶细胞杀伤的特异性。当经典补体路径的起始组分C1q结合于与靶标结合的抗体的Fc区时起始CDC。可在细胞杀伤作用的标准体内或体外分析中测定ADCC和CDC活性。用于测定ADCC和CDC活性的方法为本领域中可获得的。在一些实施方案中，所述方法可涉及用放射性物质(诸如51Cr)或荧光染料(诸如钙黄绿素-AM)标记靶细胞。可将所标记的细胞与抗体和效应细胞一起孵育，并且可通过放射性或荧光的释放来检测由ADCC或CDC产生的对靶细胞的杀伤作用。
用于测量ADCC和CDC活性的其他分析包括例如乳酸脱氢酶(LDH)释放分析。当以任何方式损害或损坏细胞膜时，细胞质中可溶而又稳定的酶LDH释放至周围的细胞间隙中。培养基中此酶的存在可用作细胞死亡标记物。然后可通过使用比色或荧光LDH细胞毒性分析测量所释放的LDH的量来定量培养基内活细胞和死细胞的相对量。
VII.包含被修饰的CH3结构域多肽的Fc区中的额外突变
如本文所提供的被修饰以结合TfR并且起始转运穿过BBB的Fc多肽还可包含额外的突变，例如以增加血清稳定性或血清半衰期，调节效应功能，影响糖基化，降低人中的免疫原性和/或提供Fc多肽的杵和臼异二聚化。
在一些实施方案中，本文所描述的被修饰的Fc多肽与对应野生型Fc多肽(例如人IgG1、IgG2、IgG3或IgG4 Fc多肽)具有至少约75％、76％、77％、78％、79％、80％、81％、82％、83％、84％、85％、86％、87％、88％、89％、90％、91％、92％、93％、94％、95％、96％、97％、98％或99％的氨基酸序列同一性。
本文所描述的被修饰的Fc多肽还可具有在指定氨基酸集合外部引入的其他突变，例如以影响糖基化，增加血清半衰期，或者对于CH3结构域，提供包含被修饰的CH3结构域的多肽的杵和臼异二聚化。通常，所述方法涉及在第一多肽的界面处引入突起(“杵”)并且在第二多肽的界面中引入对应空腔(“臼”)，使得突起可安置于空腔中以便促进异二聚体形成并且因此阻止均二聚体形成。通过将第一多肽界面的小氨基酸侧链用较大侧链(例如酪氨酸或色氨酸)置换来构建突起。通过将大氨基酸侧链用较小氨基酸侧链(例如丙氨酸或苏氨酸)置换在第二多肽的界面中形成尺寸与突起一致或类似的补偿性空腔。此类额外突变位于多肽中不对被修饰的CH3结构域与TfR的结合有负面影响的位置。
在杵和臼二聚化方法的一个说明性实施方案中，要二聚化的第一Fc多肽亚单元中对应于SEQ ID NO:1的位置136的位置具有色氨酸替代天然苏氨酸，并且二聚体的第二Fc多肽亚单元在对应于SEQ ID NO:1的位置177的位置具有缬氨酸替代天然酪氨酸。Fc多肽的第二亚单元可还包含如下取代，其中在对应于SEQ ID NO:1的位置136的位置的天然苏氨酸用丝氨酸取代，并且在对应于SEQ ID NO:1的位置138的位置的天然亮氨酸用丙氨酸取代。
还可对如本文所描述的被修饰的Fc多肽进行工程化以含有用于异二聚化的其他修饰，例如对CH3-CH3界面内天然带电荷的接触残基的静电工程化或疏水补丁修饰(hydrophobic patch modifications)。
在一些实施方案中，可引入用于增强血清半衰期的修饰。举例来说，在一些实施方案中，如本文所描述的被修饰的Fc多肽包含含有以下各项的CH2结构域：在对应于SEQ IDNO:1的位置22的位置的Tyr、在对应于SEQ ID NO:1的24的位置的Thr以及在对应于SEQ IDNO:1的位置26的位置的Glu。或者，如本文所描述的被修饰的Fc多肽可包含如参考SEQ IDNO:1编号的M198L和N204S取代。或者，如本文所描述的被修饰的Fc多肽可包含如参考SEQID NO:1编号的N204S或N204A取代。
包含额外突变的说明性Fc多肽
如本文所描述被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可包含额外的突变，包括杵突变(例如如参考SEQ ID NO:1编号的T136W)、臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))和/或增加血清稳定性或血清半衰期的突变(例如(i)如参考SEQ ID NO:1编号的M22Y、S24T以及T26E，或者(ii)如参考SEQ ID NO:1编号的N204S加上或不加上M198L)。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ IDNO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有杵突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有杵突变和调节效应功能的突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如(i)如参考SEQID NO:1编号的M22Y、S24T以及T26E，或者(ii)如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ ID NO:4-29、64-127以及268-274(例如SEQID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有杵突变以及增加血清稳定性或血清半衰期的突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如(i)如参考SEQ ID NO:1编号的M22Y、S24T以及T26E，或者(ii)如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ IDNO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有臼突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ IDNO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有臼突变和调节效应功能的突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如(i)如参考SEQ ID NO:1编号的M22Y、S24T以及T26E，或者(ii)如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ IDNO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有臼突变以及增加血清稳定性或血清半衰期的突变。
在一些实施方案中，如本文所描述的被修饰的Fc多肽(例如克隆CH3C.35.20.1、CH3C.35.23.2、CH3C.35.23.3、CH3C.35.23.4、CH3C.35.21.17.2、CH3C.35.23、CH3C.35.21、CH3C.35.20.1.1、CH3C.35.23.2.1以及CH3C.35.23.1.1中的任一者)可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如(i)如参考SEQ ID NO:1编号的M22Y、S24T以及T26E，或者(ii)如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:4-29、64-127以及268-274(例如SEQ IDNO:66、68、94、107-109、119以及268-270)中的任一者的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，可对具有SEQ ID NO:4-29、64-127以及268-274(例如SEQ ID NO:66、68、94、107-109、119以及268-270)中的任一者的序列的被修饰的Fc多肽进行修饰以具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变。
克隆CH3C.35.20.1
在一些实施方案中，克隆CH3C.35.20.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:177的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.20.1具有SEQ ID NO:177的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:178或179的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.20.1具有SEQ ID NO:178或179的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:180的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:180的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:322的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:322的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:181或182的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:181或182的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:323或324的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:323或324的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:183的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.20.1具有SEQID NO:183的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:184或185的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.20.1具有SEQ ID NO:184或185的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:186的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:186的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:325的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:325的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:187或188的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:187或188的序列。
在一些实施方案中，克隆CH3C.35.20.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:326或327的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1具有SEQ ID NO:326或327的序列。
克隆CH3C.35.23.2
在一些实施方案中，克隆CH3C.35.23.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:189的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23.2具有SEQ ID NO:189的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:190或191的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.23.2具有SEQ ID NO:190或191的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:192的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:192的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:329的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:329的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:193或194的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:193或194的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:330或331的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:330或331的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:195的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.23.2具有SEQID NO:195的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:196或197的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.23.2具有SEQ ID NO:196或197的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:198的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:198的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:332的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:332的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:199或200的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:199或200的序列。
在一些实施方案中，克隆CH3C.35.23.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:333或334的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2具有SEQ ID NO:333或334的序列。
克隆CH3C.35.23.3
在一些实施方案中，克隆CH3C.35.23.3可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:201的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23.3具有SEQ ID NO:201的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:202或203的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.23.3具有SEQ ID NO:202或203的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:204的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:204的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:336的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:336的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:205或206的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:205或206的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:337或338的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:337或338的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:207的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23.3具有SEQID NO:207的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:208或209的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.23.3具有SEQ ID NO:208或209的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:210的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:210的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:339的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:339的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:211或212的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:211或212的序列。
在一些实施方案中，克隆CH3C.35.23.3可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:340或341的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.3具有SEQ ID NO:340或341的序列。
克隆CH3C.35.23.4
在一些实施方案中，克隆CH3C.35.23.4可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:213的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23.4具有SEQ ID NO:213的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:214或215的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.23.4具有SEQ ID NO:214或215的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:216的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:216的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:343的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:343的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:217或218的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:217或218的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:344或345的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:344或345的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:219的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.23.4具有SEQID NO:219的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:220或221的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.23.4具有SEQ ID NO:220或221的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:222的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:222的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:346的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:346的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:223或224的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:223或224的序列。
在一些实施方案中，克隆CH3C.35.23.4可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:347或348的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.4具有SEQ ID NO:347或348的序列。
克隆CH3C.35.21.17.2
在一些实施方案中，克隆CH3C.35.21.17.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:225的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.21.17.2具有SEQ ID NO:225的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:226或227的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:226或227的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:228的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:228的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:350的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:350的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:229或230的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:229或230的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:351或352的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:351或352的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:231的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.21.17.2具有SEQ ID NO:231的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:232或233的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:232或233的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:234的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:234的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:353的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:353的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:235或236的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQID NO:235或236的序列。
在一些实施方案中，克隆CH3C.35.21.17.2可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:354或355的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21.17.2具有SEQ ID NO:354或355的序列。
克隆CH3C.35.23
在一些实施方案中，克隆CH3C.35.23可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:237的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23具有SEQ ID NO:237的序列。
在一些实施方案中，克隆CH3C.35.23可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:238或239的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.23具有SEQ ID NO:238或239的序列。
在一些实施方案中，克隆CH3C.35.23可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:240的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:240的序列。
在一些实施方案中，克隆CH3C.35.23可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:357的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:357的序列。
在一些实施方案中，克隆CH3C.35.23可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:241或242的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:241或242的序列。
在一些实施方案中，克隆CH3C.35.23可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:358或359的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:358或359的序列。
在一些实施方案中，克隆CH3C.35.23可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:243的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.23具有SEQ IDNO:243的序列。
在一些实施方案中，克隆CH3C.35.23可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:244或245的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.23具有SEQ ID NO:244或245的序列。
在一些实施方案中，克隆CH3C.35.23可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:246的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:246的序列。
在一些实施方案中，克隆CH3C.35.23可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:360的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:360的序列。
在一些实施方案中，克隆CH3C.35.23可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:247或248的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:247或248的序列。
在一些实施方案中，克隆CH3C.35.23可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:361或362的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23具有SEQ ID NO:361或362的序列。
克隆CH3C.35.21
在一些实施方案中，克隆CH3C.35.21可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:250的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.21具有SEQ ID NO:250的序列。
在一些实施方案中，克隆CH3C.35.21可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:252或275的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.21具有SEQ ID NO:252或275的序列。
在一些实施方案中，克隆CH3C.35.21可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:276的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:276的序列。
在一些实施方案中，克隆CH3C.35.21可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:364的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:364的序列。
在一些实施方案中，克隆CH3C.35.21可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:277或278的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:277或278的序列。
在一些实施方案中，克隆CH3C.35.21可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:365或366的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:365或366的序列。
在一些实施方案中，克隆CH3C.35.21可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:279.的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.21具有SEQ IDNO:279的序列。
在一些实施方案中，克隆CH3C.35.21可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:280或281的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.21具有SEQ ID NO:280或281的序列。
在一些实施方案中，克隆CH3C.35.21可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:282的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:282的序列。
在一些实施方案中，克隆CH3C.35.21可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:367的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:367的序列。
在一些实施方案中，克隆CH3C.35.21可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:283或284的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:283或284的序列。
在一些实施方案中，克隆CH3C.35.21可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:368或369的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.21具有SEQ ID NO:368或369的序列。
克隆CH3C.35.20.1.1
在一些实施方案中，克隆CH3C.35.20.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:285的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.20.1.1具有SEQ ID NO:285的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:286或287的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:286或287的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:288的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:288的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:371的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:371的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:289或290的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:289或290的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:372或373的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:372或373的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:291的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.20.1.1具有SEQ ID NO:291的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:292或293的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:292或293的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:294的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:294的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:374的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQ ID NO:374的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:295或296的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQID NO:295或296的序列。
在一些实施方案中，克隆CH3C.35.20.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:375或376的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.20.1.1具有SEQID NO:375或376的序列。
克隆CH3C.35.23.2.1
在一些实施方案中，克隆CH3C.35.23.2.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:297的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23.2.1具有SEQ ID NO:297的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:298或299的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:298或299的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:300的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:300的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:378的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:378的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:301或302的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:301或302的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:379或380的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:379或380的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:303的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.23.2.1具有SEQ ID NO:303的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:304或305的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:304或305的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:306的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:306的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:381的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQ ID NO:381的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:307或308的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQID NO:307或308的序列。
在一些实施方案中，克隆CH3C.35.23.2.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:382或383的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.2.1具有SEQID NO:382或383的序列。
克隆CH3C.35.23.1.1
在一些实施方案中，克隆CH3C.35.23.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)并且与SEQ ID NO:309的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变的克隆CH3C.35.23.1.1具有SEQ ID NO:309的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:310或311的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变和调节效应功能的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:310或311的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:312的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:312的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:385的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:385的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:313或314的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:313或314的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有杵突变(例如如参考SEQ ID NO:1编号的T136W)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:386或387的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有杵突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:386或387的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)并且与SEQ ID NO:315的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变的克隆CH3C.35.23.1.1具有SEQ ID NO:315的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))，并且与SEQ ID NO:316或317的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变和调节效应功能的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:316或317的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:318的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:318的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、增加血清稳定性或血清半衰期的突变(例如如参考SEQ IDNO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:388的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQ ID NO:388的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的M22Y、S24T以及T26E)，并且与SEQ ID NO:319或320的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQID NO:319或320的序列。
在一些实施方案中，克隆CH3C.35.23.1.1可具有臼突变(例如如参考SEQ ID NO:1编号的T136S、L138A以及Y177V)、调节效应功能的突变(例如如参考SEQ ID NO:1编号的L4A、L5A和/或P99G(例如L4A和L5A))、增加血清稳定性或血清半衰期的突变(例如如参考SEQ ID NO:1编号的N204S加上或不加上M198L)，并且与SEQ ID NO:389或390的序列具有至少85％同一性、至少90％同一性或至少95％同一性。在一些实施方案中，具有臼突变、调节效应功能的突变以及增加血清稳定性或血清半衰期的突变的克隆CH3C.35.23.1.1具有SEQID NO:389或390的序列。
VIII.TfR结合性蛋白质的形式
在一些实施方案中，如本文所描述的被修饰的TfR结合性多肽为蛋白质二聚体的亚单元。在一些实施方案中，二聚体为异二聚体。在一些实施方案中，二聚体为均二聚体。在一些实施方案中，二聚体包含结合于TfR受体的单一Fc多肽，即，对于TfR受体结合为单价的。在一些实施方案中，二聚体包含结合于TfR受体的第二多肽。第二多肽可包含相同的被修饰的Fc多肽以提供二价均二聚体蛋白质，或第二本文所描述的被修饰的Fc多肽可提供第二TfR受体结合位点。
本文所描述的TfR结合性多肽和包含多肽的二聚或多聚蛋白质可例如基于多肽的形式具有广泛范围的结合亲和力。举例来说，在一些实施方案中，包含如本文所描述的被修饰的Fc多肽的多肽对TfR的亲和力为1pM至10μM范围内的任一值。在一些实施方案中，可以单价形式测量亲和力。在其他实施方案中，可以二价形式测量亲和力，例如以包含被修饰的Fc多肽的蛋白质二聚体的形式测量。
用于分析结合亲和力、结合动力学以及交叉反应性以分析与TfR的结合的方法为本领域中已知的。这些方法包括但不限于固相结合分析(例如ELISA分析)、免疫沉淀、表面等离子体共振(例如BiacoreTM(GE Healthcare,Piscataway,NJ))、动力学排除分析(例如
)、流式细胞术、荧光激活细胞分选(FACS)、BioLayer干涉术(例如
(FortéBio,Inc.,Menlo Park,CA))以及西方墨点分析。在一些实施方案中，使用ELISA来测定结合亲和力和/或交叉反应性。进行ELISA分析的方法为本领域中已知的并且也描述于以下实施例部分中。在一些实施方案中，使用表面等离子体共振(SPR)来测定结合亲和力、结合动力学和/或交叉反应性。在一些实施方案中，使用动力学排除分析来测定结合亲和力、结合动力学和/或交叉反应性。在一些实施方案中，使用BioLayer干涉术分析来测定结合亲和力、结合动力学和/或交叉反应性。TfR结合性多肽的FcRn结合也可使用这些类型的分析来评估。FcRn结合典型地在酸性条件下分析，例如在约5至约6的pH值下分析。
IX.TfR结合性蛋白质缀合物
在一些实施方案中，结合TfR并且起始转运穿过BBB的被修饰的多肽包含如本文所描述的被修饰的Fc多肽并且还包含部分或全部铰链区。铰链区可来自任何免疫球蛋白亚类或同型。说明性免疫球蛋白铰链为IgG铰链区，诸如IgG1铰链区，例如人IgG1铰链氨基酸序列EPKSCDKTHTCPPCP(SEQ ID NO:62)。在其他实施方案中，可包含铰链或部分铰链区的多肽进一步融合至另一部分，例如免疫球蛋白可变区，由此产生TfR结合性多肽-可变区融合多肽。可变区可结合于任何所关注的抗原，例如治疗性神经靶标，或诊断性神经靶标。
在一些实施方案中，TfR结合性多肽(例如被修饰的Fc多肽)经由接头融合至可变区。如前一段落中所指出，TfR结合性多肽(例如被修饰的Fc多肽)可通过铰链区融合至可变区。在一些实施方案中，TfR结合性多肽(例如被修饰的Fc多肽)可通过肽接头融合至可变区。肽接头可被配置成使得它允许可变区与TfR结合性多肽相对于彼此转动；和/或对由蛋白酶消化具抗性。在一些实施方案中，接头可为柔性接头，例如含有诸如以下的氨基酸：Gly、Asn、Ser、Thr、Ala等。此类接头使用已知参数设计。举例来说，接头可具有重复，诸如Gly-Ser重复。
可变区可呈任何抗体形式，例如Fab或scFv形式。在一些实施方案中，抗体可变区序列包含两条抗体可变区重链和两条抗体可变区轻链或它们各自的片段。
TfR结合性多肽(例如被修饰的Fc多肽)还可融合至不是靶向所关注的抗原的免疫球蛋白可变区的多肽。在一些实施方案中，此类多肽使用肽接头(例如如上文所描述的柔性接头)融合至TfR结合性多肽。
在一些实施方案中，TfR结合性多肽可融合至需要靶向表达TfR结合性多肽的细胞的多肽，例如治疗性多肽。在一些实施方案中，TfR结合性多肽融合至用于转运穿过BBB的生物活性多肽，例如可溶性蛋白质，例如受体的细胞外结构域或生长因子、细胞因子或酶。
在其他实施方案中，TfR结合性多肽可融合至适用于蛋白质纯化的肽或蛋白质，例如聚组氨酸、表位标签(例如FLAG、c-Myc、血球凝集素标签等)、谷胱甘肽S转移酶(GST)、硫氧还蛋白、蛋白质A、蛋白质G或麦芽糖结合蛋白(MBP)。在一些情况下，与TfR结合性多肽融合的肽或蛋白质可包含蛋白酶裂解位点，诸如因子Xa或凝血酶的裂解位点。在某些实施方案中，键联可由存在于中枢神经系统中的酶裂解。
还可使非多肽剂连接至TfR结合性多肽。此类剂包括细胞毒性剂、显像剂、DNA或RNA分子或化合物。在一些实施方案中，所述剂可为治疗剂或显像化合物。在一些实施方案中，所述剂为小分子，例如小于1000Da、小于750Da或小于500Da。
多肽或非多肽剂可连接至TfR结合性多肽的N端或C端区，或连接至多肽的任何区域，只要所述剂不妨碍TfR结合性多肽与TfR的结合即可。
在各个实施方案中，可使用熟知化学交联试剂和方案来产生缀合物。举例来说，存在大量本领域技术人员已知并且适用于交联多肽与所关注的剂的化学交联剂。举例来说，交联剂为异双官能交联剂，所述异双官能交联剂可用于逐步键联分子。异双官能交联剂提供设计用于缀合蛋白质的更具特异性的偶联方法的能力，由此减少不希望的副反应(诸如同源蛋白质聚合物)的发生。
所关注的剂可为治疗剂，包括细胞毒性剂等，或化学部分。在一些实施方案中，所述剂可为肽或小分子治疗剂或显像剂。
X.增加效应功能的方法
对于一些应用，需要将修饰引入本文所描述的被修饰的Fc多肽或被修饰的Fc多肽二聚体中，从而增加效应功能(例如ADCC)。一种用于增加效应功能的方法涉及制备非岩藻糖基化或岩藻糖缺陷型的被修饰的Fc多肽或被修饰的Fc多肽二聚体。
一种用于产生岩藻糖缺陷型的被修饰的Fc多肽或被修饰的Fc多肽二聚体的方法为使用岩藻糖类似物，诸如2-氟代岩藻糖(2-FF)。岩藻糖类似物可消耗或降低GDP-岩藻糖的可获得性，GDP-岩藻糖为岩藻糖基转移酶将岩藻糖合并至蛋白质中所需的底物。
大规模生产常用的产生岩藻糖缺陷型的被修饰的Fc多肽或被修饰的Fc多肽二聚体的替代方法为使用α-1,6岩藻糖基转移酶(FUT8)敲出细胞系来表达被修饰的Fc多肽或被修饰的Fc多肽二聚体。适合的FUT8敲出细胞系的非限制性实例为可购自Lonza Biologics的中国仓鼠卵巢(CHO)FUT8敲出细胞系。此外，如Mori等(Biotechnol.Bioeng.(2004)88:901-908；以全文引用的方式并入本文中)中所描述，可使用FUT8小干扰RNA(siRNA)来转化CHO细胞系(例如通过FUT8 siRNA的组成性表达)以便制备岩藻糖缺陷型蛋白质。
XI.核酸、载体以及宿主细胞
典型地使用重组方法来制备如本文所描述的被修饰的TfR结合性多肽。因此，分离的核酸，所述分离的核酸所包含的核酸序列编码包含如本文所描述的被修饰的Fc多肽的多肽中的任一者，以及将所述核酸引入其中的宿主细胞，所述宿主细胞用于复制编码多肽的核酸和/或表达多肽。在一些实施方案中，宿主细胞为真核细胞，例如人细胞。
在另一方面中，提供了包含编码本文所描述的多肽的核苷酸序列的多核苷酸。多核苷酸可为单链或双链的。在一些实施方案中，多核苷酸为DNA。在特定实施方案中，多核苷酸为cDNA。在一些实施方案中，多核苷酸为RNA。
在一些实施方案中，多核苷酸包括于核酸构建体内。在一些实施方案中，构建体为可复制载体。在一些实施方案中，载体选自质粒、病毒载体、噬菌粒、酵母染色体载体以及非附加型哺乳动物载体。
在一些实施方案中，多核苷酸可操作地连接至表达构建体中的一个或多个调控核苷酸序列。在一系列实施方案中，核酸表达构建体适合于用作表面表达文库。在一些实施方案中，所述文库适合于在酵母中的表面表达。在一些实施方案中，所述文库适合于在噬菌体中的表面表达。在另一系列实施方案中，核酸表达构建体适合于使多肽在容许以毫克或克量分离多肽的系统中表达。在一些实施方案中，系统为哺乳动物细胞表达系统。在一些实施方案中，系统为酵母细胞表达系统。
用于制备重组多肽的表达媒介物包括质粒和其他载体。举例来说，适合的载体包括以下类型的质粒：pBR322衍生的质粒、pEMBL衍生的质粒、pEX衍生的质粒、pBTac衍生的质粒以及pUC衍生的质粒，用于在诸如大肠杆菌(E.coli)等原核细胞中表达。pcDNAI/amp、pcDNAI/neo、pRc/CMV、pSV2gpt、pSV2neo、pSV2-dhfr、pTk2、pRSVneo、pMSG、pSVT7、pko-neo以及pHyg衍生的载体为适合于转染真核细胞的哺乳动物表达载体的实例。或者，诸如牛乳头瘤病毒(BPV-1)或爱泼斯坦-巴尔病毒(Epstein-Barr virus)(pHEBo、pREP衍生型和p205)等病毒衍生物可用于多肽在真核细胞中的瞬时表达。在一些实施方案中，可能需要通过使用杆状病毒表达系统来表达重组多肽。此类杆状病毒表达系统的实例包括pVL衍生的载体(诸如pVL1392、pVL1393以及pVL941)、pAcUW衍生的载体(诸如pAcUW1)以及pBlueBac衍生的载体。额外的表达系统包括腺病毒、腺相关病毒以及其他病毒表达系统。
可将载体转化至任何适合的宿主细胞中。在一些实施方案中，宿主细胞(例如细菌或酵母细胞)可适合于用作表面表达文库。在一些细胞中，使载体在宿主细胞中表达以表达相对大量的多肽。此类宿主细胞包括哺乳动物细胞、酵母细胞、昆虫细胞以及原核细胞。在一些实施方案中，细胞为哺乳动物细胞，诸如中国仓鼠卵巢(CHO)细胞、幼仓鼠肾脏(BHK)细胞、NS0细胞、Y0细胞、HEK293细胞、COS细胞、维洛细胞(Vero cell)或海拉细胞(HeLacell)。
可将用编码TfR结合性多肽的表达载体转染的宿主细胞在适当条件下培养以允许发生多肽的表达。多肽可为分泌的以及从细胞混合物和含有多肽的培养基分离的。或者，多肽可保留在细胞质中或膜级分中并且收获细胞，溶解，并且使用所需方法分离多肽。
XII.实施例
包括以下实施例以展示本公开的特定实施方案。本领域技术人员应了解，以下实施例中所公开的技术代表在本公开的实践中良好起作用的技术，并且因此可被视为构成用于本公开的实践的特定模式。然而，根据本公开，本领域技术人员应了解，可在不背离本公开的精神和范围的情况下在所公开的特定实施方案中作出许多改变并且仍获得同样或类似的结果。
实施例1.TfR结合性多肽的产生
在CH3区中的特定位置使用组合文库对结合于TfR的Fc多肽进行工程化，并且针对结合于人TfR对这些文库进行选择。初始TfR结合序列的亲和力成熟使得鉴定出特定TfR结合性Fc多肽，例如具有SEQ ID NO:66的序列的Fc多肽。通过使以下三个多肽以分别1:1:2的比率共表达来构建含有异二聚Fc多肽二聚体的Fc多肽二聚体-Fab融合物。所得四聚Fc多肽二聚体-Fab融合蛋白称为BACE1-3C.35.21。
(1)含有Fab区、铰链区以及被修饰的Fc多肽(以此顺序串联地彼此融合)的重链。Fab区含有BACE1结合抗体的重链可变区。铰链区具有SEQ ID NO:62的序列。Fc多肽具有SEQID NO:250的序列并且含有“杵”突变(根据EU编号方案为T366W)和TfR结合性突变。
(2)含有Fab区、铰链区以及被修饰的Fc多肽(以此顺序串联地彼此融合)的重链。Fab区含有BACE1结合抗体的重链可变区。铰链区具有SEQ ID NO:62的序列。Fc多肽具有SEQID NO:251的序列并且含有“臼”突变(根据EU编号方案为T366S、L368A以及Y407V)。
(3)含有BACE1结合抗体的轻链可变区的轻链。
将编码用于表达以上三个多肽的基因的DNA克隆至表达载体中并且以分别1:1:2的比率转染至ExpiCHO细胞(Thermo Fisher Scientific)中。在5-7天之后，收获细胞，并且将所得多肽使用本领域技术人员熟悉的方法依次通过蛋白质A和HIC纯化。通过质谱法分析所得多肽以证实在纯化之后不存在具有均二聚Fc多肽二聚体的融合蛋白(即，两个Fc多肽均具有“杵”突变的Fc多肽二聚体，或两个Fc多肽均具有“臼”突变的Fc多肽二聚体)。类似地产生额外的四聚体多肽。
实施例2.人顶端结构域敲入小鼠(人TfR敲入(TfRms/hu KI)小鼠)的产生
产生敲入/敲出小鼠的方法在文献中已公布并且为本领域技术人员熟知的。概括地说，使用CRISPR/Cas9技术产生TfRms/hu KI小鼠以表达鼠Tfrc基因内的人Tfrc顶端结构域；使所得嵌合TfR在内源性启动子的控制下在体内表达。如以全文引用的方式并入本文中的国际专利申请号PCT/US2018/018302中所描述，使用C57Bl6小鼠经由原核微量注射至单细胞胚胎中，随后胚胎移植至假妊娠雌性中来产生人顶端TfR小鼠品系的敲入。特定而言，将Cas9、具有SEQ ID NO:264和265的序列的单一向导RNA以及具有SEQ ID NO:267的序列的供体DNA引入胚胎中。供体DNA包含人顶端结构域编码序列(SEQ ID NO:266，所述序列已针对在小鼠中表达进行密码子优化)。顶端结构域编码序列侧接左侧同源臂(SEQ ID NO:267的核苷酸1-817)和右侧同源臂(SEQ ID NO:267的核苷酸1523-2329)。以使得顶端结构域插入第四小鼠外显子之后，并且在3'端紧密侧接第九小鼠外显子的方式来设计供体序列。可使来自接受胚胎的雌性的子代的首建雄性(founder male)与野生型雌性繁殖以产生F1杂合子小鼠。随后由培育F1代杂合子小鼠产生纯合子小鼠。
实施例3.在两个Fc多肽中具有LALA突变的TfR结合性Fc多肽阻止小鼠中的网织红细胞消耗
当向小鼠施用时结合于TfR的抗体已显示消耗循环网织红细胞与骨髓网织红细胞两者(参见例如Couch等,Sci Transl Med,5:183ra57,1-12,2013)。产生了类似于实施例1中描述的BACE1-3C.35.21的Fc多肽二聚体-Fab融合物。所述Fc多肽二聚体-Fab融合物称为“BACE1-3C.35.212XLALA”，含有以下各项：(1)含有具有BACE1结合性抗体的重链可变区的Fab区、铰链区以及被修饰的Fc多肽的重链，所述被修饰的Fc多肽具有“杵”突变(根据EU编号方案为T366W)、降低效应功能的突变(根据EU编号方案为L234A和L235A)以及TfR结合性突变(抗BACE1 Fab区融合至铰链区(SEQ ID NO:62)和SEQ ID NO:252(具有杵和LALA突变的克隆CH3C.35.21))；(2)含有具有BACE1结合性抗体的重链可变区的Fab区、铰链区以及被修饰的Fc多肽的重链，所述被修饰的Fc多肽具有“臼”突变(根据EU编号方案的T366S、L368A以及Y407V)和降低效应功能的突变(根据EU编号方案的L234A和L235A)(抗BACE1 Fab区融合至铰链区(SEQ ID NO:62)和SEQ ID NO:253(具有臼突变和LALA突变的人Fc序列))；以及(3)两条轻链，所述两条轻链各自包含BACE1结合性抗体的轻链可变区。
产生纯合子人TfR敲入(TfRms/hu KI)小鼠以在体内评估Fc多肽二聚体-Fab融合蛋白。简单来说，对这些小鼠进行工程化以用人顶端结构域/小鼠嵌合TfR蛋白置换小鼠TfR(参见实施例2)。以25mg/kg给予这些小鼠BACE1-Fc二聚体2XLALAPG(融合至在两个Fc多肽中具有LALA突变和P329G突变(根据EU编号方案)的Fc二聚体的抗BACE1 Fab)或BACE1-3C.35.212XLALA。在给药后24小时时分别通过CBC和FACS分析评估循环和骨髓网织红细胞。将骨髓网织红细胞鉴定为Ter119+、hCD71高以及FSC低群体。与先前的研究一致，称为“BACE1-3C.35.212XLALA”的Fc多肽二聚体-Fab融合物不诱导体内网织红细胞消耗(图1A和图1B)，这类似于非TfR结合性Fc多肽二聚体。
实施例4.具有不对称LALA突变的TfR结合性Fc多肽的设计
TfR在网织红细胞上高度表达，网织红细胞为存在于骨髓与循环中的不成熟红血球。先前已证实具有完全效应功能的TfR抗体可快速消耗血液与骨髓中的网织红细胞。因此，对于基于TfR的抗体治疗剂，网织红细胞的消耗负主要安全责任。然而，完全去除基于TfR的抗体中的效应功能并非妥善解决方案，因为在一些情况下，在工程化的TfR结合性Fc区融合至治疗剂Fab的情况下将需要在Fab结合后触发效应功能，而在TfR结合后不触发效应功能。因为诸如根据EU编号方案的L234A和L235A(LALA)等Fc突变使FcγR结合于Fc多肽二聚体减少，所以在Fc多肽二聚体的两个Fc多肽上含有此类突变的融合至Fab的工程化的TfR结合性Fc多肽二聚体在TfR结合或Fab结合于靶标的情况下不能引发任何效应功能。
需要当Fab结合于其靶标时可引发效应功能，但当TfR结合位点结合于TfR时不引发效应功能的融合至治疗剂Fab的工程化的TfR结合性Fc多肽二聚体。为此目的，研发了两个Fc多肽中的一者含有(而另一者不含)当结合于TfR时减少FcγR结合的突变的Fc多肽二聚体。如以下表1和表2中所描述产生了融合至结合于BACE1、人CD20(hCD20)或小鼠CD20(mCD20)的抗原结合Fab区的在一个Fc多肽中含有LALA突变、在两个Fc多肽中含有LALA突变或两个Fc多肽中均不含LALA突变的一系列TfR结合性Fc多肽二聚体。表1描述了两条重链中的每一者的Fc区中的突变。在表1中所描述的所有变体中，重链1在Fc区中含有TfR结合位点和杵突变T366W(根据EU编号方案)，并且重链2在Fc区中含有臼突变T366S、L368A以及Y407V(根据EU编号方案)。变体zz-3C.35.21在Fc区中不含任何额外突变；变体zz-3C.35.212xLALA在重链1与重链2的两个Fc区中均含有LALA突变；变体zz-3C.35.21顺LALA在一个Fc区中含有LALA突变，所述Fc区与还含有TfR结合位点的Fc区相同(顺LALA或顺式构型)；变体zz-3C.35.21反LALA在一个Fc区中含有LALA突变，所述Fc区不含TfR结合位点(反LALA或反式构型)。同样的情况适用于变体zz-3C.35.23、变体zz-3C.35.232xLALA、变体zz-3C.35.23顺LALA以及变体zz-3C.35.23反LALA。
表2列举了每种Fc多肽二聚体-Fab融合物的每条重链和轻链的SEQ ID NO。举例来说，BACE1-3C.35.212xLALA含有表1中描述的变体zz-3C.35.212xLALA和靶向BACE1的Fab区。
表1.Fc多肽中的效应功能突变
| 变体名称 | 重链1：TfR结合性Fc(杵) | 重链2：Fc(臼) |
| zz-3C.35.21 | 无 | 无 |
| zz-3C.35.21<sup>2xLALA</sup> | LALA | LALA |
| zz-3C.35.21<sup>顺LALA</sup> | LALA | 无 |
| zz-3C.35.21<sup>反LALA</sup> | 无 | LALA |
| zz-3C.35.23 | 无 | 无 |
| zz-3C.35.23<sup>2xLALA</sup> | LALA | LALA |
| zz-3C.35.23<sup>顺LALA</sup> | LALA | 无 |
| zz-3C.35.23<sup>反LALA</sup> | 无 | LALA |
表2.Fc多肽二聚体-Fab融合物的SEQ ID NO
实施例5.具有顺式构型的TfR结合性多肽使小鼠中的网织红细胞消耗减轻
为确定是具有顺式构型还是具有反式构型的Fc多肽二聚体可减轻网织红细胞消耗，我们用这些Fc多肽二聚体以及野生型人IgG(hIgG)对应物对纯合子人TfR敲入(TfRms/huKI)小鼠进行处理，并且分析了这些动物中来自外周血与骨髓的网织红细胞。使用Advia120血液学系统从外周血定量循环网织红细胞。简单来说，将细胞用ADVIA autoRETIC试剂染色并且基于RNA含量和差异光吸收对网织红细胞进行鉴定。对于骨髓网织红细胞，从每种动物的股骨收获骨髓细胞，用Fc封闭剂(抗小鼠CD16/CD32)封闭，用抗mTer119和抗hCD71染色，并且通过荧光激活细胞分选(FACS)进行分析。使用FlowJo分析软件将网织红细胞门控为mTer119+、hCD71高以及FSC低群体。在分析后，具有顺式构型(即，仅一个Fc多肽含有TfR结合位点与LALA突变两者，而另一Fc多肽既不含TfR结合位点也不含LALA突变)的Fc多肽二聚体缓和血液与骨髓中的网织红细胞损失，血液与骨髓中的网织红细胞损失以其他方式可见于野生型hIgG对照和具有反式构型(即，一个Fc多肽含有TfR结合位点，而另一Fc多肽含有LALA突变)的Fc多肽二聚体中。显著地，具有顺式构型的Fc多肽二聚体在25mg/kg下不具有主要安全责任，主要安全责任一般见于具有效应功能的TfR结合性多肽中(图2A和图2B)。此外，使用具有较低TfR亲和力的TfR结合性多肽用在50mg/kg下的更高剂量对系统施加应力。虽然顺式构型部分减轻血液网织红细胞损失，但更反应临床安全性的骨髓网织红细胞损失未受影响(图2C和图2D)。另一方面，具有反式构型的Fc多肽二聚体以与野生型IgG对照类似的量值消耗血液和骨髓网织红细胞。这些结果证实具有顺式构型的Fc多肽二聚体能够缓和体内网织红细胞损失。
实施例6.具有顺式构型的TfR结合性多肽使TfR介导的体外ADCC活性减轻
经确定没有由具有顺式构型的Fc多肽二聚体引起的体内网织红细胞损失是归因于它不能引发TfR介导的ADCC。使用表达高水平的人TfR的拉莫斯细胞作为体外ADCC分析中的靶细胞。将靶细胞以10,000个细胞/孔进行涂铺并且用以下各项调理30分钟：(1)具有TfR结合位点的hIgG1，(2)具有TfR结合位点并且在两个Fc多肽中具有LALA突变的hIgG1，以及(3)具有含有顺式构型的Fc多肽二聚体的hIgG1。从人外周血分离效应自然杀手(NK)细胞，在IL-21(20ng/mL)存在下孵育过夜，并且以25:1的效应细胞:靶细胞比率与靶细胞一起(250,000个细胞/孔)孵育4h。通过LDH表达评估细胞毒性，针对不具有任何多肽的对照进行校正，并且计算为在靶细胞中的最大溶解百分比。因为效应免疫细胞(在此情况下为自然杀手细胞)表达FcγR，故野生型IgG1的Fc部分将结合于FcγR并且触发ADCC反应。实际上，具有TfR结合位点的hIgG1引发稳健ADCC反应，而在两个Fc多肽中具有LALA突变的hIgG1与具有含有顺式构型的Fc多肽二聚体的hIgG1两者均不引发稳健ADCC反应。此数据与体内网织红细胞数据一致：具有顺式构型的Fc多肽二聚体以及在两个Fc多肽上(以两种不同TfR亲和力：图3A：CH3C.35.21；图3B：CH3C.35.23)均具有TfR结合位点和LALA突变的Fc多肽二聚体阻止TfR介导的ADCC并且因此缓和网织红细胞消耗。
实施例7.TfR结合性多肽阻止TfR介导的体外CDC活性
由结合于TfR的抗体引起的体内网织红细胞损失还可来源于TfR介导的CDC。有趣的是，结合于TfR的Fc多肽二聚体不能引发CDC，这可能是归因于它不能在空间上形成多肽六聚物以触发补体反应。将经过工程化以过表达TfR的CHO细胞(CHO-hTfR)以200,000个细胞/孔涂铺于不含血清的培养基中。将细胞用以下各项调理30分钟：(1)对照hIgG，(2)Ab204(抗TfR阳性对照抗体)，以及(3)具有TfR结合位点的hIgG1。将50μL的稀幼兔血清添加至每个孔中并且将细胞孵育4h。通过LDH表达评估细胞毒性，针对不具有任何多肽的对照进行校正，并且计算为在靶细胞中的最大溶解百分比。实际上，虽然抗TfR Ab204能够在CHO-hTfR细胞中诱导CDC，但在Fc区具有TfR结合位点的hIgG1对CDC没有影响(图4)。
实施例8.具有顺式构型的TfR结合性多肽刺激原代人小神经胶质细胞中的pSyk活性
使用原代人小胶质细胞，证实了被修饰的Fc多肽二聚体如通过FcγR诱导的磷酸化脾脏酪氨酸激酶(pSYK)活性所确定具有功能性Fc。效应免疫细胞上的FcγR一般结合于抗体的Fc区以触发许多对先天免疫重要的反应。那些反应中的一者包括Syk酪氨酸激酶信号传导路径，所述Syk酪氨酸激酶信号传导路径在免疫细胞活化中发挥重要作用，诸如噬菌作用、细胞因子释放以及ADCC(DeFranco等,J.of Exp Med.,1997,186(7):1027-39)。当免疫细胞的FcγR结合于免疫复合物时，基于免疫受体酪氨酸的活化基序(ITAM)使Syk激酶能够被募集并且由Src家族激酶磷酸化，这引起下游信号传导路径，从而触发免疫细胞活化(Hirose等,J of Biol Chem,2004,279:32308-15)。因此，使用pSyk作为FcγR诱导的免疫细胞活化的读出。收获来自衍生自人胎儿组织的混合神经胶质细胞培养物的小胶质细胞并且用于评估在结合于TfR结合性多肽后人小胶质细胞中的pSyk活性。然后将小神经胶质细胞添加至TfR结合性多肽包被的96孔板上，在37℃下孵育10min，溶解，并且使用pSyk夹心免疫分析定量pSyk的水平。尽管顺-LALA突变不引发TfR介导的ADCC，但它类似于野生型IgG肽能够在人小胶质细胞中引发pSyk反应(相较于LALA突变对照增加约3倍，图5)。此结果证实，具有顺式构型的被修饰的Fc多肽二聚体保留其Fc功能并且可具有效应功能。
实施例9.具有顺式构型的TfR结合性多肽在靶细胞中引发Fab介导的ADCC和CDC
除pSYK活性诱导之外，还评估了具有顺式构型的TfR结合性多肽引发Fab介导的ADCC和CDC的能力。使用表达小鼠CD20的靶细胞(A20细胞系)来评估Fab介导的ADCC。类似于实施例8中描述的TfR介导的ADCC，将靶细胞以10,000个细胞/孔进行涂铺，调理，以25:1的效应细胞:靶细胞比率与NK细胞一起孵育，并且通过LDH表达评估细胞毒性。将靶细胞用以下各项进行调理：(1)对照hIgG，(2)抗mCD20抗体，(3)具有TfR结合位点和mCD20 Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-mCD20(WT))，以及(4)具有含有顺式构型的Fc多肽二聚体以及mCD20 Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-mCD20(顺-LALA))。所述分析被设计成仅用于评估Fab结合，因为靶细胞不表达人TfR。与pSYK活性诱导一致，具有含有顺式构型的Fc多肽二聚体以及mCD20 Fab结合位点的hIgG1引发类似于抗mCD20抗体以及具有TfR结合位点和mCD20 Fab结合位点的hIgG1的ADCC(图6A)。
除ADCC之外，还评估了CDC。先前已显示拉吉细胞(Raji cell)在抗hCD20介导的CDC中为敏感的；因此，使用它们作为靶细胞来评估具有TfR结合位点和hCD20 Fab结合位点的hIgG1。将拉吉细胞以200,000个细胞/孔涂铺于不含血清的培养基中并且用以下各项调理30分钟：(1)对照hIgG，(2)抗hCD20抗体，(3)具有TfR结合位点和hCD20 Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-hCD20(WT))，以及(4)具有含有顺式构型的Fc多肽二聚体以及hCD20 Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-hCD20(顺-LALA))。将50μL的稀幼兔血清添加至每个孔中并且将细胞孵育4h。通过LDH表达评估细胞毒性，针对不具有任何多肽的对照进行校正，并且计算为在靶细胞中的最大溶解百分比。类似于Fab介导的ADCC，具有含有顺式构型的Fc多肽二聚体以及hCD20 Fab结合位点的hIgG1引发的CDC所达到的程度与抗hCD20以及具有TfR结合位点和hCD20 Fab结合位点的hIgG1相同(图6B)。总的来说，这些功能性体外细胞毒性分析证实具有含有顺式构型的Fc多肽二聚体的hIgG1不妨碍其引发Fab介导的效应功能的能力。
实施例10.具有顺式构型和mCD20 Fab结合位点的TfR结合性多肽引发体内效应功能
如体内安全分析中所证实，具有含有顺式构型的Fc多肽二聚体的hIgG1缓和结合于TfR后的网织红细胞损失。然后我们测试了此构型是否会引发Fab介导的体内效应功能，Fab介导的体内效应功能对诱导治疗反应来说必不可少。先前已证实针对mCD20的抗体严重消耗体内外周和脾B细胞并且因此已用于评估Fab介导的效应功能。在WT小鼠中评估了具有含有顺式构型的Fc多肽二聚体以及mCD20 Fab结合位点的hIgG1消耗血液和脾B细胞的能力，并且与在抗mCD20抗体以及具有TfR结合位点和mCD20 Fab结合位点的hIgG1中所观测到的反应相比较。用以下各项以25mg/kg对WT小鼠进行处理：(1)对照IgG，(2)抗mCD20抗体，(3)具有TfR结合位点和mCD20 Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-mCD20(WT))，(4)具有TfR结合位点并且在两个Fc多肽中具有LALA突变并且具有mCD20Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-mCD20(LALA))，以及(5)具有含有顺式构型的Fc多肽二聚体以及mCD20 Fab结合位点的hIgG1(CH3C.35.21 hIgG1:α-mCD20(顺-LALA))。分别在第1天和第5天评估成熟外周B细胞和脾B细胞。简单来说，收获外周血和脾脏。将来自外周血和脾细胞的细胞用ACK溶解缓冲液处理，与Fc封闭剂一起孵育，并且用抗B220和抗IgM染色。在FACS分析后将成熟B细胞鉴定为B220高IgM高群体。与Fab介导的体外ADCC和CDC分析一致，具有含有顺式构型的Fc多肽二聚体以及mCD20 Fab结合位点的hIgG1引发类似于抗mCD20抗体以及具有TfR结合位点和mCD20 Fab结合位点的hIgG1的稳健B细胞消耗(图7A和图7B)。这些结果证实具有顺式构型的被修饰的Fc多肽二聚体保留其Fc功能并且具有Fab介导的体内效应功能。
实施例11.结合于TfR的被修饰的Fc多肽
此实施例描述了为赋予TfR结合并且转运穿过BBB而对Fc多肽的修饰。
除非另外指出，否则本部分中氨基酸残基的位置是基于对人IgG1野生型Fc区的EU索引编号来编号。
在位置384、386、387、388、389、390、413、416以及421包含修饰的Fc多肽(CH3C克
隆)的产生和表征
如下文所描述产生含有Fc区的酵母文库，所述Fc区具有引入包括氨基酸位置384、386、387、388、389、390、413、416以及421的位置中的修饰。表3和表4中示出了结合于TfR的说明性克隆。
在再两轮分选之后，对单一克隆进行测序并且鉴定出四个独特序列。这些序列具有在位置388的保守Trp，并且全部具有在位置421的芳族残基(即，Trp、Tyr或His)。在其他位置存在极大的多样性。
使选自所述文库的四个克隆以在CHO或293细胞中表达为Fc与Fab片段的融合物，并且通过蛋白质A和尺寸排阻色谱纯化，然后在存在或不存在全铁Tf(holo-Tf)的情况下通过ELISA针对与人TfR结合进行筛检。所述克隆全部结合于人TfR并且结合不因添加过量(5μM)全铁Tf而受影响。还针对与内源性表达人TfR的293F细胞的结合对克隆进行测试。克隆结合于293F细胞，不过总体结合大体上弱于高亲和力阳性对照。
然后，使用克隆CH3C.3作为测试克隆来测试克隆是否可内化于TfR表达细胞中。使附着的HEK 293细胞在96孔板中生长至约80％汇合，去除培养基，并且以1μM的浓度添加样品：克隆CH3C.3、抗TfR基准阳性对照抗体(Ab204)、抗BACE1基准阴性对照抗体(Ab107)以及人IgG同型对照(从Jackson Immunoresearch获得)。将细胞在37℃和8％CO2浓度下孵育30分钟，然后洗涤，用0.1％TritonTM X-100透性化，并且用抗人-IgG-Alexa
488二级抗体染色。在再洗涤之后，使细胞在高通量荧光显微镜(即，Opera PhenixTM系统)下成像，并且定量每一细胞的斑点数目。在1μM下，克隆CH3C.3显示与阳性抗TfR对照类似的内化倾向，而阴性对照未显示内化。
克隆的进一步工程化
使用软随机化法(soft randomization approach)产生额外的文库以改善初始命中物(hit)对人TfR的亲和力，其中基于原始四个命中物中的每一者产生DNA寡核苷酸以引入软诱变(soft mutagenesis)。鉴定结合TfR的额外的克隆并且加以选择。所选克隆属于两个一般序列组。组1克隆(即，克隆CH3C.18、CH3C.21、CH3C.25以及CH3C.34)具有在位置384的半保守Leu、在位置386的Leu或His、分别在位置387和389的保守和半保守Val以及分别在位置413、416以及421的半保守P-T-W基序。组2克隆具有在位置384的保守Tyr、在位置386-390的基序TXWSX以及分别在位置413、416以及421的保守基序S/T-E-F。将克隆CH3C.18和CH3C.35用于额外的研究中作为每个序列组的代表性成员。
表位定位
为确定工程化的Fc区是否结合于TfR的顶端结构域，使TfR顶端结构域在噬菌体的表面表达。为适当折叠并且展示顶端结构域，必须将环中的一者截短并且需要将序列环形排列。将克隆CH3C.18和CH3C.35包被于ELISA板上并且进行噬菌体ELISA方案。简单来说，在洗涤并且用1％PBSA封闭之后，添加噬菌体展示物的稀释液并且在室温下孵育1小时。随后将板洗涤并且添加抗M13-HRP，并且在再洗涤之后用TMB底物使板显色并且用2N H2SO4中止反应。在此分析中克隆CH3C.18与CH3C.35均结合于顶端结构域。
互补位定位
为理解Fc结构域中哪些残基对TfR结合来说最重要，形成一系列突变体克隆CH3C.18和克隆CH3C.35Fc区，其中每种突变体在TfR结合登记者中有单一位置突变回野生型。使所得变体重组表达为Fab-Fc融合物并且针对与人或犬TfR结合进行测试。对于克隆CH3C.35，位置388和421对结合来说为重要的；这些位置中的任一者恢复为野生型均完全消除与人TfR的结合。
成熟克隆的结合表征
如上文所描述，在存在包被于板上的人或犬TfR的情况下用纯化的Fab-Fc融合变体进行结合ELISA。来自克隆CH3C.18成熟文库的变体克隆CH3C.3.2-1、克隆CH3C.3.2-5以及克隆CH3C.3.2-19以大致相等的EC50值结合人和犬TfR，而亲本克隆CH3C.18和CH3C.35相较于犬TfR与人TfR具有大于10倍的更佳的结合。
然后，测试被修饰的Fc多肽是否内化于人和猴细胞中。使用上文所描述的方案，测试在人HEK 293细胞和恒河猴LLC-MK2细胞中的内化。与克隆CH3C.35相比，类似地结合人和犬TfR的变体克隆CH3C.3.2-5和CH3C.3.2-19在LLC-MK2细胞中具有显著改善的内化。
克隆的额外工程化
对其他亲和力成熟克隆CH3C.18和CH3C.35的额外工程化涉及向通过直接相互作用、第二壳相互作用(second-shell interaction)或结构稳定化增强结合的位置添加额外突变。这是经由产生“NNK行走(NNK walk)”或“NNK补丁(NNK patch)”文库以及由其选择来实现。NNK行走文库涉及形成靠近互补位的残基的逐个NNK突变。通过查看Fc结合于FcγRI的结构(PDB ID：4W4O)，将靠近原始修饰位置的44个残基鉴定为询问候选残基。特定而言，靶向以下残基进行NNK诱变：K248、R255、Q342、R344、E345、Q347、T359、K360、N361、Q362、S364、K370、E380、E382、S383、G385、Y391、K392、T393、D399、S400、D401、S403、K409、L410、T411、V412、K414、S415、Q418、Q419、G420、V422、F423、S424、S426、Q438、S440、S442、L443、S444、P4458、G446以及K447。使用孔克尔诱变(Kunkel mutagenesis)产生44单点NNK文库，并且将产物汇集并且如上文关于其他酵母文库所描述经由电穿孔引入酵母。
这些迷你文库(其中的每一者具有一个突变位置，从而产生20个变体)的组合产生小文库，针对引起较高亲和力结合的任何位置使用酵母表面展示对所述小文库加以选择。使用TfR顶端结构域蛋白质如上文所描述进行选择。在三轮分选之后，对来自富集酵母文库的克隆进行测序，并且鉴定出若干“热点”位置，在所述位置中某些点突变显著改善与顶端结构域蛋白质的结合。对于克隆CH3C.35，这些突变包括E380(突变为Trp、Tyr、Leu或Gln)和S415(突变为Glu)。SEQ ID NO:21-23、64-69以及125-127中阐述了克隆CH3C.35单一和组合突变体的序列。对于克隆CH3C.18，这些突变包括E380(突变为Trp、Tyr或Leu)和K392(突变为Gln、Phe或His)。SEQ ID NO:70-75中阐述了克隆CH3C.18单一突变体的序列。
用于改善克隆CH3C.35亲和力的额外成熟文库
如关于先前的酵母文库所描述产生用于鉴定来自NNK行走文库的突变组合，同时添加在这些位置周边的若干额外位置的另一文库。在此文库中，YxTEWSS(SEQ ID NO:414)和TxxExxxxF(SEQ ID NO:415)基序保持恒定，并且六个位置为完全随机化的：E380、K392、K414、S415、S424以及S426。包括位置E380和S415，因为它们是NNK行走文库中的“热点”。包括位置K392、S424以及S426，因为它们构成可定位结合区的核心的一部分，同时选择K414，这是归因于它的邻近位置415。
仅使用犬TfR顶端结构域如先前所描述对此文库进行分选。在五轮之后对富集汇集物进行测序，并且SEQ ID NO:76-93中阐述了所鉴定的独特克隆的被修饰区域的序列。
以接下来的文库进行设计以进一步探索在主要结合互补位中可接受的多样性。用NNK密码子将原始位置(384、386、387、388、389、390、413、416以及421)中的每一者加上两个热点(380和415)个别地随机化以产生一系列基于酵母的单位置饱和诱变文库。此外，将每个位置个别地恢复为野生型残基，并且使这些个别克隆展示于酵母上。应注意，位置380、389、390以及415为仅有的在恢复为野生型残基后保留与TfR的实质性结合的位置(对于413恢复为野生型，观测到一定程度残留但极大程度减弱的结合)。
将单位置NNK文库针对人TfR顶端结构域分选三轮以收集最前的约5％的结合者，然后从每个文库对至少16个克隆进行测序。结果指示在克隆CH3C.35的背景下，在每个位置在不显著降低与人TfR的结合的情况下可忍受什么氨基酸。概述如下：
位置380：Trp、Leu或Glu；
位置384：Tyr或Phe；
位置386：仅Thr；
位置387：仅Glu；
位置388：仅Trp；
位置389：Ser、Ala或Val(虽然野生型Asn残基似乎保留一些结合，但它在文库分选之后不出现)；
位置390：Ser或Asn；
位置413：Thr或Ser；
位置415：Glu或Ser；
位置416：仅Glu；以及
位置421：仅Phe。
以上残基当作为单一变化或以组合形式取代至克隆CH3C.35中时呈现保留与TfR顶端结构域结合的互补位多样性。在这些位置具有突变的克隆包括表4中所示的那些克隆，并且SEQ ID NO:65-69、92、94-124以及268-274中阐述了这些克隆的CH3结构域的序列。
实施例12.方法
噬菌体展示文库的产生
合成编码野生型人Fc序列的DNA模板并且合并至噬菌粒载体中。噬菌粒载体含有ompA或pelB前导序列、融合至c-Myc和6xHis(SEQ ID NO:421)表位标签的Fc插入物以及在M13外壳蛋白pIII之后的琥珀(amber)终止密码子。
产生在用于修饰的所需位置含有“NNK”三密码子的引物，其中N为任何DNA碱基(即，A、C、G或T)并且K为G或T。或者，使用用于“软”随机化的引物，其中将对应于70％野生型碱基和10％其他三种碱基中的每一者的碱基的混合物用于每个随机化位置。通过进行对应于随机化区域的Fc区片段的PCR扩增来产生文库，然后使用含有SfiI限制位点的末端引物进行组装，然后用SfiI消化并且连结至噬菌粒载体中。或者，使用引物来进行孔克尔诱变。将连结产物或孔克尔产物转化至菌株TG1(从
获得)的电转感受态大肠杆菌细胞中。在回收之后使大肠杆菌细胞感染M13K07辅助噬菌体并且生长过夜，此后将文库噬菌体用5％PEG/NaCl沉淀，再悬浮于含15％甘油的PBS中，并且冷冻直到使用。典型文库尺寸在约109至约1011个转化体范围内。经由pIII融合的Fc与不附着于pIII的可溶性Fc(后者因pIII前的琥珀终止密码子而产生)之间的配对使Fc-二聚体展示于噬菌体上。
酵母展示文库的产生
合成编码野生型人Fc序列的DNA模板并且合并至酵母展示载体中。对于CH2和CH3文库，使Fc多肽展示于Aga2p细胞壁蛋白质上。两种载体均含有具有Kex2裂解序列的前原前导肽前体(prepro leader peptide)，并且c-Myc表位标签融合至Fc末端。
使用类似于关于噬菌体文库所描述的那些方法的方法来组装酵母展示文库，除了使用含有对载体同源的末端的引物来进行片段扩增。用线性化的载体和组装的文库插入物对新制备的电转感受态酵母(即，菌株EBY100)进行电穿孔。电穿孔方法将为本领域技术人员已知的。在选择性SD-CAA培养基中回收之后，使酵母生长至汇合并且分裂两次，然后通过转移至SG-CAA培养基来诱导蛋白质表达。典型文库尺寸在约107至约109个转化体范围内。通过邻近展示的Fc单体的配对形成Fc-二聚体。
噬菌体选择的一般方法
噬菌体方法由Phage Display:A Laboratory Manual(Barbas,2001)改编而来。从此参考文献可获得额外的方案细节。
板分选法
在4℃下将人TfR靶标包被于
微量滴定板上(典型地200μL，于PBS中1-10μg/mL)过夜。除非另有规定，否则所有结合均在室温下进行。将噬菌体文库添加至每个孔中并且孵育过夜以便结合。将微量滴定孔用含有0.05％
20(PBST)的PBS彻底洗涤并且通过将孔在酸(典型地为50mM HCl加上500mM KCl，或100mM甘氨酸，pH 2.7)存在下孵育30分钟将结合的噬菌体洗脱。将洗脱的噬菌体用1M Tris(pH 8)中和并且使用TG1细胞和M13/KO7辅助噬菌体扩增，并且在37℃下在含有50μg/mL羧苄西林(carbenacillin)和50μg/mL卡那霉素(Kanamycin)的2YT培养基中生长过夜。将从含有靶标的孔洗脱的噬菌体的效价与从不含靶标的孔中回收的噬菌体的效价相比较以评估富集。通过随后减少结合期间的孵育时间以及增加洗涤时间和洗涤次数来增加选择严格性。
珠粒分选法
使用NHS-PEG4-生物素(从PierceTM获得)通过游离胺将抗原生物素化。对于生物素化反应，在PBS中使用3倍至5倍摩尔过量的生物素试剂。用Tris中止反应，随后在PBS中彻底渗析。将生物素化的抗原固定于链霉亲和素包被的磁性珠粒(即，从Thermo Fisher获得的M280-链霉亲和素珠粒)上。将噬菌体展示文库与抗原包被的珠粒在室温下一起孵育1小时。然后去除未结合的噬菌体并且用PBST洗涤珠粒。通过在存在含有500mM KCl的50mM HCl(或0.1M甘氨酸，pH 2.7)的情况下孵育30分钟将结合的噬菌体洗脱，然后如上文关于板分选所描述进行中和和增殖。
在三至五轮淘选之后，通过使Fc在噬菌体上表达或在大肠杆菌周质中可溶性表达来筛选单一克隆。此类表达方法将为本领域技术人员已知的。使个别噬菌体上清液或周质提取物暴露于包被有抗原或阴性对照的封闭的ELISA板，并且随后对于周质提取物使用HRP缀合的山羊抗Fc(从Jackson Immunoresearch获得)或对于噬菌体使用抗M13(GEHealthcare)进行检测，然后用TMB试剂(从Thermo Fisher获得)显色。将OD450值大于约5倍于背景的孔视为阳性克隆并且测序，此后使一些克隆作为可溶性Fc片段或以融合至Fab片段的形式表达。
酵母选择的一般方法
珠粒分选(磁性辅助细胞分选(MACS))法
类似于Ackerman等,2009Biotechnol.Prog.,25(3),774中所描述进行MACS和FACS选择。将链霉亲和素磁性珠粒(例如来自Thermo Fisher的M-280链霉亲和素珠粒)用生物素化的抗原标记并且与酵母一起孵育(典型地5-10x文库多样性)。去除未结合的酵母，洗涤珠粒，并且使结合的酵母在选择性培养基中生长并且诱导后续各轮选择。
荧光激活细胞分选(FACS)法
将酵母用抗c-Myc抗体标记以监测表达和生物素化的抗原(浓度根据各轮分选而变化)。在一些实验中，将抗原与链霉亲和素-Alexa 
647预混合以增强相互作用的亲合力。在其他实验中，在结合并且用链霉亲和素-Alexa
647洗涤之后检测到生物素化的抗原。使用FACS Aria III细胞分选器对结合情况下的单线态酵母进行分选。使分选的酵母在选择性培养基中生长，然后诱导后续各轮选择。
在实现富集酵母群体之后，将酵母涂铺于SD-CAA琼脂板上并且使单一菌落生长并且诱导表达，然后如上文所描述进行标记以测定它们结合于靶标的倾向。随后针对结合抗原对阳性单一克隆进行测序，此后一些克隆作为可溶性Fc片段或以融合至Fab片段的形式表达。
筛选的一般方法
通过ELISA筛选
从淘选输出端选择克隆并且使其在96孔深孔板的个别孔中生长。使用自动诱导培养基(从EMD Millipore获得)诱导克隆的周质表达或使其感染辅助噬菌体以使个别Fc变体于噬菌体上发生噬菌体展示。使培养物生长过夜并且离心以使大肠杆菌集结成粒。对于噬菌体ELISA，直接使用含有噬菌体的上清液。对于周质表达，将球粒再悬浮于20％蔗糖中，随后用水以4:1稀释，并且在4℃下振荡1小时。将板离心以使固体集结成粒并且将上清液用于ELISA中。
将ELISA板典型地以0.5mg/mL用抗原包被过夜，然后用1％BSA封闭，然后添加噬菌体或周质提取物。在1小时孵育和洗去未结合的蛋白质之后，添加HRP缀合的二级抗体(即，对于可溶性Fc或噬菌体展示的Fc分别为抗Fc或抗M13)并且孵育30分钟。再次将板洗涤，然后用TMB试剂显色并且用2N硫酸中止反应。使用读板仪
定量在450nm下的吸光度并且在适当时使用Prism软件绘制结合曲线。将所测试的克隆的吸光度信号与阴性对照(缺乏Fc的噬菌体或周质(paraplasmic)提取物)相比较。在一些分析中，在结合步骤期间典型地以显著摩尔过量添加可溶性转铁蛋白或其他竞争物(大于10倍过量)。
通过流式细胞术筛选
将Fc变体多肽(表达于噬菌体上、周质提取物中或作为与Fab片段的融合物可溶性表达)添加至96孔V形底板中的孔中(在PBS+1％BSA(PBSA)中每孔约100,000个细胞)，并且在4℃下孵育1小时。随后将板离心并且去除培养基，然后将细胞用PBSA洗涤一次。将细胞再悬浮于含有二级抗体(典型地为山羊抗人-IgG-Alexa
647(从Thermo Fisher获得))的PBSA中。在30分钟之后，将板离心并且去除培养基，将细胞用PBSA洗涤1-2次，然后将板在流式细胞仪(即，FACSCantoTMII流式细胞仪)上读取。使用FlowJo软件计算每种条件下的中值荧光值并且用Prism软件绘制结合曲线。
实施例13.CH3C.18变体的构建
此实施例描述了CH3C.18变体的文库的构建。
分离单一克隆，并且在补充有0.2％葡萄糖的SG-CAA培养基中生长过夜以诱导CH3C.18变体的表面表达。对于每种克隆，将两百万个细胞在PBS+0.5％BSA(pH 7.4)中洗涤三次。在4℃下在振荡的同时，将细胞用生物素化靶标250nM人TfR、250nM犬TfR或250nM的不相关生物素化蛋白质染色1小时，然后用相同缓冲液洗涤两次。在4℃下，将细胞用中性亲和素(nuetravidin)-Alexafluor647(AF647)染色30分钟，然后再洗涤两次。使用抗c-myc抗体加上抗鸡-Alexfluor488(AF488)二级抗体测量表达。将细胞再悬浮，并且在BD FACSCantoII上测量AF647和AF488的中值荧光强度(MFI)。计算各群体的TfR结合群体的MFI并且在人TfR、犬TfR或对照结合情况下绘制曲线。
表5示出了CH3C.18变体的文库。每一列表示在每个位置含有所指示的氨基酸取代的变体并且其余位置的氨基酸与CH3C.18中相同。表5中所示的位置是根据EU编号方案编号。
表5.CH3C.18变体
实施例14.具有顺式构型和结合淀粉样蛋白β(Aβ)的Fab的TfR结合性多肽有效穿过BBB并且引发稳健效应功能，从而使得小胶质细胞募集至Aβ斑块并且Aβ斑块小鼠模型中斑块减少
为提供具有顺式构型的TfR结合性多肽可用于治疗相关疾病模型中的额外证据，我们在Aβ斑块沉淀小鼠模型中评估了具有结合Aβ的Fab的具有顺式构型的TfR结合性Fc多肽。特定而言，评估了这些多肽将小神经胶质细胞募集至Aβ斑块的能力。简单来说，在第0天、第3天、第6天以及第9天按以下组以50mg/kg对动物(3.5月龄)进行腹膜内处理：1)用对照IgG处理TfRms/hu KI小鼠(n＝6)，2)用对照IgG处理5XFAD x TfRms/hu KI小鼠(n＝11)，3)用抗Aβ(α-Aβ)处理5XFAD x TfRms/hu KI小鼠(n＝12)，4)用具有顺式构型和AβFab结合位点的TfR结合性Fc多肽处理5XFAD x TfRms/hu KI小鼠(n＝12)，以及5)用在两个Fc多肽上具有LALA突变的TfR结合性Fc多肽处理5XFAD x TfRms/hu KI小鼠(n＝12)。表6列举了每种Fc多肽二聚体-Fab融合物的每条重链和轻链的SEQ ID NO。
表6.Fc多肽二聚体-Fab融合物的SEQ ID NO
在第12天，对小鼠进行灌注；收集脑并且以40μm进行矢状面切片用于免疫组织化学分析。每个动物选择两个脑切片(切片1：外侧至中线约3mm，切片2：在中线处)用于IHC分析。将自由浮动切片在封闭溶液(含0.3％triton X-100的5％驴血清的PBS溶液)中在室温下孵育两小时，然后与一级抗体(抗CD68，抗人Aβ)一起在4℃下孵育过夜。然后将切片洗涤3次持续15分钟，与荧光标记的二级抗体一起在室温下孵育2h，与DAPI溶液一起孵育20分钟，然后在含0.3％triton X-100的PBS中洗涤3次。将切片安装至载玻片上并且使用延时玻璃抗荧光衰减封片剂(Prolong Glass Antifade mounting medium)加盖玻片。使用ZeissAxioscan.Z1载玻片扫描仪以20X放大倍数使载玻片成像并且使用Zeiss ZEN软件中的定制宏和图像处理宏进行处理。特定而言，分析图像以测定扩大的斑块面积(根据尺寸)、斑块/CD68小神经胶质细胞重叠的面积、扩大的CD68+小神经胶质细胞面积、计数和像素强度总和(根据尺寸：9-14μm2、14-33μm2、33-75μm2以及75-3,333μm2)以及斑块形态、面积、计数和像素强度总和(使用紧密度将圆形与不规则斑块分开，<0.7为不规则而>0.7为圆形；根据尺寸分开：30-125μm2、125-250μm2、250-500μm2以及500-3,300μm2)。
由这些实验，用具有顺-LALA Fc多肽二聚体情况下的TfR结合位点的抗Aβ处理的5XFAD x TfRms/hu KI小鼠以类似于抗Aβ的方式引发稳健的小胶质细胞朝向Aβ斑块的募集(如通过小胶质细胞标记物CD68和Aβ标记物的共定位所测量)并且使尺寸为30-125μm2的较小斑块减少(图8A至图8C)。重要地，在两个Fc多肽上具有TfR结合位点并且具有LALA突变的抗Aβ的情况下未观测到这些影响，这与这些疾病模式中效应功能的必要性相符合。总的说来，这些数据与本文中的其他体外和体内数据一起提供如下强有力的证据，具有顺-LALA构型的TfR结合性Fc多肽的平台主链和相关Fab结合位点可缓和网织红细胞安全性，并且在相关疾病模型中引发靶标介导的效应功能(即，脑中的小胶质细胞参与)。
应了解，本文所描述的实施例和实施方案仅用于说明性目的，并且将向本领域技术人员建议根据它们进行的各种修改或变化，并且所述修改或变化应包括在本申请的精神和权限以及随附权利要求书的范围内。本文引用的序列登录号的序列以引用的方式并入本文中。
除非另外定义，否则本文中所用的所有技术和科学术语具有与一般熟习本发明所属技术者通常所理解相同的含义。
可在不存在本文中未特定公开的任何一种元件或多种元件、一种限制或多种限制的情况下适当地实践本文中说明性地描述的发明。因此，举例来说，术语“包含”、“包括”、“含有”等应可扩展地加以阅读并且不限于此。另外，本文所使用的术语和表述是用作描述术语而非限制术语，并且在使用此类术语和表述时不意在排除所显示和描述的特征的任何等效物或其部分，但应认识到，在本发明所要求的范围内各种修改均为可能的。
在有差异的情况下，表格(例如表3和表4)中所描述的每种克隆的氨基酸取代指示所述克隆在登记位置对存在于序列表中所阐述的序列中的氨基酸的氨基酸取代。
本文提到的所有出版物、专利申请、专利以及其他参考文献以全文引用的方式明确并入本文中，所达到的程度与各自以引用的方式个别地并入相同。在矛盾的情况下，将以本说明书，包括定义为准。
表3.CH3C登记位置和突变
表4.额外的CH3C登记位置和突变
非正式序列表
序列表
<110> 戴纳立制药公司(DENALI THERAPEUTICS INC.)
<120> 转铁蛋白受体结合性多肽和其用途
<130> 102342-001740PC-1118620
<140>
<141>
<150> 62/721,275
<151> 2018-08-22
<150> 62/682,639
<151> 2018-06-08
<150> 62/631,281
<151> 2018-02-15
<150> 62/615,914
<151> 2018-01-10
<160> 421
<170> PatentIn version 3.5
<210> 1
<211> 217
<212> PRT
<213> 智人(Homo sapiens)
<400> 1
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 2
<211> 110
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 2
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys
100 105 110
<210> 3
<211> 107
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 3
Gly Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp
1 5 10 15
Glu Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe
20 25 30
Tyr Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu
35 40 45
Asn Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe
50 55 60
Phe Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly
65 70 75 80
Asn Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr
85 90 95
Thr Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys
100 105
<210> 4
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 4
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly Leu Val Trp Val Gly
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ala Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 5
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 5
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Val Trp Ser His
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Tyr Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 6
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 6
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Gln
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Glu Lys Ser Asp Trp Gln Gln Gly His Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 7
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 7
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Val Gly Thr Pro Trp Ala Leu
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Leu Lys Ser Glu Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 8
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 8
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Val Trp Ser Lys
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 9
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 9
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 10
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 10
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly Leu Val Trp Val Gly
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 11
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 11
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Met Gly His Val Trp Val Gly
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 12
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 12
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly Leu Val Trp Val Phe
145 150 155 160
Ser Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 13
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 13
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 14
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 14
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 15
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 15
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Val Gly
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 16
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 16
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Val Ala
145 150 155 160
Thr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 17
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 17
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly Pro Val Trp Val His
145 150 155 160
Thr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 18
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 18
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Val Asp
145 150 155 160
Gln Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 19
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 19
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Val Asn
145 150 155 160
Gln Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 20
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 20
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Val Asn
145 150 155 160
Phe Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 21
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 21
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 22
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 22
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 23
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 23
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 24
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 24
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 25
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 25
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 26
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 26
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 27
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 27
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 28
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 28
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 29
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 29
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 30
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<220>
<221> MOD_RES
<222> (154)..(154)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (156)..(160)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (183)..(183)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (185)..(186)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (191)..(191)
<223> 氨基酸
<400> 30
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Xaa Gly Xaa Xaa Xaa Xaa Xaa
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Xaa Lys Xaa Xaa Trp Gln Gln Gly Xaa Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 31
<211> 181
<212> PRT
<213> 智人(Homo sapiens)
<400> 31
Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg Leu Val Tyr Leu Val
1 5 10 15
Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr Val Thr
20 25 30
Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe Glu Asp
35 40 45
Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala Gly Lys
50 55 60
Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn Ala Ile
65 70 75 80
Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val Asn Ala
85 90 95
Glu Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp Pro Tyr
100 105 110
Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro Ser Arg
115 120 125
Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg Ala Ala
130 135 140
Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser Asp Trp
145 150 155 160
Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser Glu Ser Lys Asn Val
165 170 175
Lys Leu Thr Val Ser
180
<210> 32
<211> 181
<212> PRT
<213> 食蟹猴(Macaca fascicularis)
<400> 32
Asn Ser Val Ile Ile Val Asp Lys Asn Gly Gly Leu Val Tyr Leu Val
1 5 10 15
Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr Val Thr
20 25 30
Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe Glu Asp
35 40 45
Leu Asp Ser Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala Gly Lys
50 55 60
Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn Ala Ile
65 70 75 80
Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val Lys Ala
85 90 95
Asp Leu Ser Phe Phe Gly His Ala His Leu Gly Thr Gly Asp Pro Tyr
100 105 110
Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln Phe Pro Pro Ser Gln
115 120 125
Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg Ala Ala
130 135 140
Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser Asp Trp
145 150 155 160
Lys Thr Asp Ser Thr Cys Lys Met Val Thr Ser Glu Asn Lys Ser Val
165 170 175
Lys Leu Thr Val Ser
180
<210> 33
<211> 159
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 33
Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg Ala Ala
1 5 10 15
Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser Asp Trp
20 25 30
Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser Glu Ser Lys Asn Val
35 40 45
Lys Leu Thr Val Ser Asn Asp Ser Ala Gln Asn Ser Val Ile Ile Val
50 55 60
Asp Lys Asn Gly Arg Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr
65 70 75 80
Val Ala Tyr Ser Lys Ala Ala Thr Val Thr Gly Lys Leu Val His Ala
85 90 95
Asn Phe Gly Thr Lys Lys Asp Phe Glu Asp Leu Tyr Thr Pro Val Asn
100 105 110
Gly Ser Ile Val Ile Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys
115 120 125
Val Ala Asn Ala Glu Ser Leu Asn Ala Ile Gly Val Leu Ile Tyr Met
130 135 140
Asp Gln Thr Lys Phe Pro Ile Val Asn Ala Glu Leu Ser Gly Pro
145 150 155
<210> 34
<211> 159
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 34
Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr Ile Ser Arg Ala Ala
1 5 10 15
Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp Cys Pro Ser Asp Trp
20 25 30
Lys Thr Asp Ser Thr Cys Lys Met Val Thr Ser Glu Asn Lys Ser Val
35 40 45
Lys Leu Thr Val Ser Asn Asp Ser Ala Gln Asn Ser Val Ile Ile Val
50 55 60
Asp Lys Asn Gly Gly Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr
65 70 75 80
Val Ala Tyr Ser Lys Ala Ala Thr Val Thr Gly Lys Leu Val His Ala
85 90 95
Asn Phe Gly Thr Lys Lys Asp Phe Glu Asp Leu Asp Ser Pro Val Asn
100 105 110
Gly Ser Ile Val Ile Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys
115 120 125
Val Ala Asn Ala Glu Ser Leu Asn Ala Ile Gly Val Leu Ile Tyr Met
130 135 140
Asp Gln Thr Lys Phe Pro Ile Val Lys Ala Asp Leu Ser Gly Pro
145 150 155
<210> 35
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<220>
<221> MOD_RES
<222> (4)..(4)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (6)..(10)
<223> 氨基酸
<400> 35
Trp Glu Ser Xaa Gly Xaa Xaa Xaa Xaa Xaa Tyr Lys
1 5 10
<210> 36
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<220>
<221> MOD_RES
<222> (3)..(3)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (5)..(6)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (11)..(11)
<223> 氨基酸
<400> 36
Thr Val Xaa Lys Xaa Xaa Trp Gln Gln Gly Xaa Val
1 5 10
<210> 37
<211> 5
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 37
Tyr Gly Thr Glu Trp
1 5
<210> 38
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 38
Leu Gly Leu Val Trp Val Gly
1 5
<210> 39
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 39
Tyr Gly Thr Val Trp Ser His
1 5
<210> 40
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 40
Tyr Gly Thr Glu Trp Ser Gln
1 5
<210> 41
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 41
Val Gly Thr Pro Trp Ala Leu
1 5
<210> 42
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 42
Tyr Gly Thr Val Trp Ser Lys
1 5
<210> 43
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 43
Leu Gly His Val Trp Ala Val
1 5
<210> 44
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 44
Met Gly His Val Trp Val Gly
1 5
<210> 45
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 45
Leu Gly Leu Val Gly Val Phe
1 5
<210> 46
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 46
Tyr Gly Thr Glu Trp Ser Ser
1 5
<210> 47
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 47
Tyr Gly Thr Glu Trp Ser Asn
1 5
<210> 48
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 48
Leu Gly His Val Trp Val Gly
1 5
<210> 49
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 49
Leu Gly His Val Trp Val Ala
1 5
<210> 50
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 50
Leu Gly Pro Val Trp Val His
1 5
<210> 51
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 51
Leu Gly His Val Trp Val Asp
1 5
<210> 52
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 52
Leu Gly His Val Trp Val Asn
1 5
<210> 53
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 53
Ala Lys Ser Thr Trp Gln Gln Gly Trp
1 5
<210> 54
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 54
Ser Lys Ser Glu Trp Gln Gln Gly Tyr
1 5
<210> 55
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 55
Glu Lys Ser Asp Trp Gln Gln Gly His
1 5
<210> 56
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 56
Leu Lys Ser Glu Trp Gln Gln Gly Trp
1 5
<210> 57
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 57
Ser Lys Ser Glu Trp Gln Gln Gly Phe
1 5
<210> 58
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 58
Pro Lys Ser Thr Trp Gln Gln Gly Trp
1 5
<210> 59
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 59
Asp Lys Ser Thr Trp Gln Gln Gly Trp
1 5
<210> 60
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 60
Thr Lys Ser Glu Trp Gln Gln Gly Phe
1 5
<210> 61
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 61
Ser Lys Ser Glu Trp Gln Gln Gly Trp
1 5
<210> 62
<211> 15
<212> PRT
<213> 智人(Homo sapiens)
<400> 62
Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro
1 5 10 15
<210> 63
<211> 760
<212> PRT
<213> 智人(Homo sapiens)
<400> 63
Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu
1 5 10 15
Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp
20 25 30
Asn Ser His Val Glu Met Lys Leu Ala Val Asp Glu Glu Glu Asn Ala
35 40 45
Asp Asn Asn Thr Lys Ala Asn Val Thr Lys Pro Lys Arg Cys Ser Gly
50 55 60
Ser Ile Cys Tyr Gly Thr Ile Ala Val Ile Val Phe Phe Leu Ile Gly
65 70 75 80
Phe Met Ile Gly Tyr Leu Gly Tyr Cys Lys Gly Val Glu Pro Lys Thr
85 90 95
Glu Cys Glu Arg Leu Ala Gly Thr Glu Ser Pro Val Arg Glu Glu Pro
100 105 110
Gly Glu Asp Phe Pro Ala Ala Arg Arg Leu Tyr Trp Asp Asp Leu Lys
115 120 125
Arg Lys Leu Ser Glu Lys Leu Asp Ser Thr Asp Phe Thr Gly Thr Ile
130 135 140
Lys Leu Leu Asn Glu Asn Ser Tyr Val Pro Arg Glu Ala Gly Ser Gln
145 150 155 160
Lys Asp Glu Asn Leu Ala Leu Tyr Val Glu Asn Gln Phe Arg Glu Phe
165 170 175
Lys Leu Ser Lys Val Trp Arg Asp Gln His Phe Val Lys Ile Gln Val
180 185 190
Lys Asp Ser Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn Gly Arg
195 200 205
Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys
210 215 220
Ala Ala Thr Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys
225 230 235 240
Lys Asp Phe Glu Asp Leu Tyr Thr Pro Val Asn Gly Ser Ile Val Ile
245 250 255
Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu
260 265 270
Ser Leu Asn Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe
275 280 285
Pro Ile Val Asn Ala Glu Leu Ser Phe Phe Gly His Ala His Leu Gly
290 295 300
Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln
305 310 315 320
Phe Pro Pro Ser Arg Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr
325 330 335
Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp
340 345 350
Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser
355 360 365
Glu Ser Lys Asn Val Lys Leu Thr Val Ser Asn Val Leu Lys Glu Ile
370 375 380
Lys Ile Leu Asn Ile Phe Gly Val Ile Lys Gly Phe Val Glu Pro Asp
385 390 395 400
His Tyr Val Val Val Gly Ala Gln Arg Asp Ala Trp Gly Pro Gly Ala
405 410 415
Ala Lys Ser Gly Val Gly Thr Ala Leu Leu Leu Lys Leu Ala Gln Met
420 425 430
Phe Ser Asp Met Val Leu Lys Asp Gly Phe Gln Pro Ser Arg Ser Ile
435 440 445
Ile Phe Ala Ser Trp Ser Ala Gly Asp Phe Gly Ser Val Gly Ala Thr
450 455 460
Glu Trp Leu Glu Gly Tyr Leu Ser Ser Leu His Leu Lys Ala Phe Thr
465 470 475 480
Tyr Ile Asn Leu Asp Lys Ala Val Leu Gly Thr Ser Asn Phe Lys Val
485 490 495
Ser Ala Ser Pro Leu Leu Tyr Thr Leu Ile Glu Lys Thr Met Gln Asn
500 505 510
Val Lys His Pro Val Thr Gly Gln Phe Leu Tyr Gln Asp Ser Asn Trp
515 520 525
Ala Ser Lys Val Glu Lys Leu Thr Leu Asp Asn Ala Ala Phe Pro Phe
530 535 540
Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe Cys Glu Asp
545 550 555 560
Thr Asp Tyr Pro Tyr Leu Gly Thr Thr Met Asp Thr Tyr Lys Glu Leu
565 570 575
Ile Glu Arg Ile Pro Glu Leu Asn Lys Val Ala Arg Ala Ala Ala Glu
580 585 590
Val Ala Gly Gln Phe Val Ile Lys Leu Thr His Asp Val Glu Leu Asn
595 600 605
Leu Asp Tyr Glu Arg Tyr Asn Ser Gln Leu Leu Ser Phe Val Arg Asp
610 615 620
Leu Asn Gln Tyr Arg Ala Asp Ile Lys Glu Met Gly Leu Ser Leu Gln
625 630 635 640
Trp Leu Tyr Ser Ala Arg Gly Asp Phe Phe Arg Ala Thr Ser Arg Leu
645 650 655
Thr Thr Asp Phe Gly Asn Ala Glu Lys Thr Asp Arg Phe Val Met Lys
660 665 670
Lys Leu Asn Asp Arg Val Met Arg Val Glu Tyr His Phe Leu Ser Pro
675 680 685
Tyr Val Ser Pro Lys Glu Ser Pro Phe Arg His Val Phe Trp Gly Ser
690 695 700
Gly Ser His Thr Leu Pro Ala Leu Leu Glu Asn Leu Lys Leu Arg Lys
705 710 715 720
Gln Asn Asn Gly Ala Phe Asn Glu Thr Leu Phe Arg Asn Gln Leu Ala
725 730 735
Leu Ala Thr Trp Thr Ile Gln Gly Ala Ala Asn Ala Leu Ser Gly Asp
740 745 750
Val Trp Asp Ile Asp Asn Glu Phe
755 760
<210> 64
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 64
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 65
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 65
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 66
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 66
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 67
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 67
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 68
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 68
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 69
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 69
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 70
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 70
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 71
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 71
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 72
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 72
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Tyr Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 73
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 73
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 74
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 74
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr Phe Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 75
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 75
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Ala Val
145 150 155 160
Tyr His Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 76
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 76
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 77
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 77
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 78
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 78
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 79
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 79
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Gly Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 80
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 80
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 81
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 81
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 82
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 82
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Thr Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 83
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 83
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Thr Cys Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 84
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 84
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Glu Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 85
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 85
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Lys Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 86
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 86
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Pro Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Lys Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 87
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 87
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 88
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 88
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Gly Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 89
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 89
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Thr Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 90
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 90
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Gly Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Thr Cys Trp Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 91
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 91
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Arg Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Thr Cys Gly Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 92
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 92
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 93
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 93
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Arg Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 94
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 94
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 95
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 95
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 96
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 96
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 97
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 97
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 98
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 98
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 99
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 99
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Val Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 100
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 100
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 101
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 101
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 102
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 102
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Val Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 103
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 103
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 104
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 104
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Phe Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 105
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 105
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Phe Gly Thr Glu Trp Val Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 106
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 106
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 107
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 107
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 108
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 108
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 109
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 109
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 110
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 110
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 111
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 111
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 112
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 112
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 113
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 113
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 114
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 114
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 115
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 115
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 116
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 116
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Phe Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 117
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 117
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Phe Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 118
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 118
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 119
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 119
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 120
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 120
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Val Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 121
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 121
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 122
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 122
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Phe Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 123
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 123
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Phe Gly Thr Glu Trp Val Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 124
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 124
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 125
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 125
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Leu Gly His Val Trp Val Asn
145 150 155 160
Gln Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 126
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 126
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Leu Gly His Val Trp Val Asn
145 150 155 160
Gln Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 127
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 127
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Leu Gly His Val Trp Val Asn
145 150 155 160
Gln Gln Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 128
<211> 760
<212> PRT
<213> 食蟹猴(Macaca fascicularis)
<400> 128
Met Met Asp Gln Ala Arg Ser Ala Phe Ser Asn Leu Phe Gly Gly Glu
1 5 10 15
Pro Leu Ser Tyr Thr Arg Phe Ser Leu Ala Arg Gln Val Asp Gly Asp
20 25 30
Asn Ser His Val Glu Met Lys Leu Gly Val Asp Glu Glu Glu Asn Thr
35 40 45
Asp Asn Asn Thr Lys Ala Asn Gly Thr Lys Pro Lys Arg Cys Gly Gly
50 55 60
Asn Ile Cys Tyr Gly Thr Ile Ala Val Ile Ile Phe Phe Leu Ile Gly
65 70 75 80
Phe Met Ile Gly Tyr Leu Gly Tyr Cys Lys Gly Val Glu Pro Lys Thr
85 90 95
Glu Cys Glu Arg Leu Ala Gly Thr Glu Ser Pro Ala Arg Glu Glu Pro
100 105 110
Glu Glu Asp Phe Pro Ala Ala Pro Arg Leu Tyr Trp Asp Asp Leu Lys
115 120 125
Arg Lys Leu Ser Glu Lys Leu Asp Thr Thr Asp Phe Thr Ser Thr Ile
130 135 140
Lys Leu Leu Asn Glu Asn Leu Tyr Val Pro Arg Glu Ala Gly Ser Gln
145 150 155 160
Lys Asp Glu Asn Leu Ala Leu Tyr Ile Glu Asn Gln Phe Arg Glu Phe
165 170 175
Lys Leu Ser Lys Val Trp Arg Asp Gln His Phe Val Lys Ile Gln Val
180 185 190
Lys Asp Ser Ala Gln Asn Ser Val Ile Ile Val Asp Lys Asn Gly Gly
195 200 205
Leu Val Tyr Leu Val Glu Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys
210 215 220
Ala Ala Thr Val Thr Gly Lys Leu Val His Ala Asn Phe Gly Thr Lys
225 230 235 240
Lys Asp Phe Glu Asp Leu Asp Ser Pro Val Asn Gly Ser Ile Val Ile
245 250 255
Val Arg Ala Gly Lys Ile Thr Phe Ala Glu Lys Val Ala Asn Ala Glu
260 265 270
Ser Leu Asn Ala Ile Gly Val Leu Ile Tyr Met Asp Gln Thr Lys Phe
275 280 285
Pro Ile Val Lys Ala Asp Leu Ser Phe Phe Gly His Ala His Leu Gly
290 295 300
Thr Gly Asp Pro Tyr Thr Pro Gly Phe Pro Ser Phe Asn His Thr Gln
305 310 315 320
Phe Pro Pro Ser Gln Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr
325 330 335
Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp
340 345 350
Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Lys Met Val Thr Ser
355 360 365
Glu Asn Lys Ser Val Lys Leu Thr Val Ser Asn Val Leu Lys Glu Thr
370 375 380
Lys Ile Leu Asn Ile Phe Gly Val Ile Lys Gly Phe Val Glu Pro Asp
385 390 395 400
His Tyr Val Val Val Gly Ala Gln Arg Asp Ala Trp Gly Pro Gly Ala
405 410 415
Ala Lys Ser Ser Val Gly Thr Ala Leu Leu Leu Lys Leu Ala Gln Met
420 425 430
Phe Ser Asp Met Val Leu Lys Asp Gly Phe Gln Pro Ser Arg Ser Ile
435 440 445
Ile Phe Ala Ser Trp Ser Ala Gly Asp Phe Gly Ser Val Gly Ala Thr
450 455 460
Glu Trp Leu Glu Gly Tyr Leu Ser Ser Leu His Leu Lys Ala Phe Thr
465 470 475 480
Tyr Ile Asn Leu Asp Lys Ala Val Leu Gly Thr Ser Asn Phe Lys Val
485 490 495
Ser Ala Ser Pro Leu Leu Tyr Thr Leu Ile Glu Lys Thr Met Gln Asp
500 505 510
Val Lys His Pro Val Thr Gly Arg Ser Leu Tyr Gln Asp Ser Asn Trp
515 520 525
Ala Ser Lys Val Glu Lys Leu Thr Leu Asp Asn Ala Ala Phe Pro Phe
530 535 540
Leu Ala Tyr Ser Gly Ile Pro Ala Val Ser Phe Cys Phe Cys Glu Asp
545 550 555 560
Thr Asp Tyr Pro Tyr Leu Gly Thr Thr Met Asp Thr Tyr Lys Glu Leu
565 570 575
Val Glu Arg Ile Pro Glu Leu Asn Lys Val Ala Arg Ala Ala Ala Glu
580 585 590
Val Ala Gly Gln Phe Val Ile Lys Leu Thr His Asp Thr Glu Leu Asn
595 600 605
Leu Asp Tyr Glu Arg Tyr Asn Ser Gln Leu Leu Leu Phe Leu Arg Asp
610 615 620
Leu Asn Gln Tyr Arg Ala Asp Val Lys Glu Met Gly Leu Ser Leu Gln
625 630 635 640
Trp Leu Tyr Ser Ala Arg Gly Asp Phe Phe Arg Ala Thr Ser Arg Leu
645 650 655
Thr Thr Asp Phe Arg Asn Ala Glu Lys Arg Asp Lys Phe Val Met Lys
660 665 670
Lys Leu Asn Asp Arg Val Met Arg Val Glu Tyr Tyr Phe Leu Ser Pro
675 680 685
Tyr Val Ser Pro Lys Glu Ser Pro Phe Arg His Val Phe Trp Gly Ser
690 695 700
Gly Ser His Thr Leu Ser Ala Leu Leu Glu Ser Leu Lys Leu Arg Arg
705 710 715 720
Gln Asn Asn Ser Ala Phe Asn Glu Thr Leu Phe Arg Asn Gln Leu Ala
725 730 735
Leu Ala Thr Trp Thr Ile Gln Gly Ala Ala Asn Ala Leu Ser Gly Asp
740 745 750
Val Trp Asp Ile Asp Asn Glu Phe
755 760
<210> 129
<211> 186
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 129
Met Gly Trp Ser Cys Ile Ile Leu Phe Leu Val Ala Thr Ala Thr Gly
1 5 10 15
Ala Tyr Ala Gly Thr Ser Ser Gly Leu Pro Asn Ile Pro Val Gln Thr
20 25 30
Ile Ser Arg Ala Ala Ala Glu Lys Leu Phe Gly Asn Met Glu Gly Asp
35 40 45
Cys Pro Ser Asp Trp Lys Thr Asp Ser Thr Cys Arg Met Val Thr Ser
50 55 60
Glu Ser Lys Asn Val Lys Leu Thr Val Ser Asn Asp Ser Ala Gln Asn
65 70 75 80
Ser Val Ile Ile Val Asp Lys Asn Gly Arg Leu Val Tyr Leu Val Glu
85 90 95
Asn Pro Gly Gly Tyr Val Ala Tyr Ser Lys Ala Ala Thr Val Thr Gly
100 105 110
Lys Leu Val His Ala Asn Phe Gly Thr Lys Lys Asp Phe Glu Asp Leu
115 120 125
Tyr Thr Pro Val Asn Gly Ser Ile Val Ile Val Arg Ala Gly Lys Ile
130 135 140
Thr Phe Ala Glu Lys Val Ala Asn Ala Glu Ser Leu Asn Ala Ile Gly
145 150 155 160
Val Leu Ile Tyr Met Asp Gln Thr Lys Phe Pro Ile Val Asn Ala Glu
165 170 175
Leu Ser Ala Ser His His His His His His
180 185
<210> 130
<211> 244
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 130
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Lys Thr His Thr Cys Pro Ala Pro Glu Ala Ala
20 25 30
Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu
35 40 45
Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val Asp Val Ser
50 55 60
His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu
65 70 75 80
Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr
85 90 95
Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn
100 105 110
Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Gly Ala Pro
115 120 125
Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln
130 135 140
Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val
145 150 155 160
Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val
165 170 175
Glu Trp Glu Ser Leu Gly His Val Trp Ala Val Tyr Lys Thr Thr Pro
180 185 190
Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr
195 200 205
Val Pro Lys Ser Thr Trp Gln Gln Gly Trp Val Phe Ser Cys Ser Val
210 215 220
Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu
225 230 235 240
Ser Pro Gly Lys
<210> 131
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 131
Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
1 5 10
<210> 132
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 132
Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
1 5 10
<210> 133
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 133
Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Ser
1 5 10
<210> 134
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 134
Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
1 5 10
<210> 135
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 135
Glu Trp Glu Ser Phe Gly Thr Glu Trp Ala Ser
1 5 10
<210> 136
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 136
Glu Trp Glu Ser Phe Gly Thr Glu Trp Val Ser
1 5 10
<210> 137
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 137
Trp Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
1 5 10
<210> 138
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 138
Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
1 5 10
<210> 139
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 139
Trp Trp Glu Ser Tyr Gly Thr Glu Trp Val Ser
1 5 10
<210> 140
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 140
Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
1 5 10
<210> 141
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 141
Trp Trp Glu Ser Phe Gly Thr Glu Trp Ala Ser
1 5 10
<210> 142
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 142
Trp Trp Glu Ser Phe Gly Thr Glu Trp Val Ser
1 5 10
<210> 143
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 143
Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
1 5 10
<210> 144
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 144
Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
1 5 10
<210> 145
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 145
Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
1 5 10
<210> 146
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 146
Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
1 5 10
<210> 147
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 147
Glu Trp Glu Ser Phe Gly Thr Glu Trp Ala Asn
1 5 10
<210> 148
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 148
Glu Trp Glu Ser Phe Gly Thr Glu Trp Val Asn
1 5 10
<210> 149
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 149
Trp Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
1 5 10
<210> 150
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 150
Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
1 5 10
<210> 151
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 151
Trp Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
1 5 10
<210> 152
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 152
Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
1 5 10
<210> 153
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 153
Trp Trp Glu Ser Phe Gly Thr Glu Trp Ala Asn
1 5 10
<210> 154
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 154
Trp Trp Glu Ser Phe Gly Thr Glu Trp Val Asn
1 5 10
<210> 155
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 155
Leu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
1 5 10
<210> 156
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 156
Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
1 5 10
<210> 157
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 157
Leu Trp Glu Ser Tyr Gly Thr Glu Trp Val Ser
1 5 10
<210> 158
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 158
Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
1 5 10
<210> 159
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 159
Leu Trp Glu Ser Phe Gly Thr Glu Trp Ala Ser
1 5 10
<210> 160
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 160
Leu Trp Glu Ser Phe Gly Thr Glu Trp Val Ser
1 5 10
<210> 161
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 161
Trp Trp Glu Ser Leu Gly His Val Trp Ala Val
1 5 10
<210> 162
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 162
Glu Trp Glu Ser Leu Gly His Val Trp Ala Val
1 5 10
<210> 163
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 163
Leu Trp Glu Ser Leu Gly His Val Trp Ala Val
1 5 10
<210> 164
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 164
Tyr Trp Glu Ser Leu Gly His Val Trp Ala Val
1 5 10
<210> 165
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 165
Glu Trp Glu Ser Leu Gly Leu Val Trp Val Phe
1 5 10
<210> 166
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 166
Trp Trp Glu Ser Leu Gly His Val Trp Val Asn
1 5 10
<210> 167
<211> 11
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 167
Glu Trp Glu Ser Leu Gly His Val Trp Val Asn
1 5 10
<210> 168
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 168
Thr Lys Glu Glu Trp Gln Gln Gly Phe
1 5
<210> 169
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 169
Ser Lys Glu Glu Trp Gln Gln Gly Phe
1 5
<210> 170
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 170
Pro Lys Thr Ser Trp Gln Gln Gly Trp
1 5
<210> 171
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 171
Thr Arg Glu Glu Trp Gln Gln Gly Phe
1 5
<210> 172
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 172
Thr Pro Glu Glu Trp Gln Gln Gly Phe
1 5
<210> 173
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<400> 173
Thr Gly Glu Glu Trp Gln Gln Gly Phe
1 5
<210> 174
<211> 12
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<220>
<221> MOD_RES
<222> (3)..(3)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (5)..(6)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (11)..(11)
<223> 氨基酸
<400> 174
Thr Val Xaa Lys Xaa Xaa Trp Gln Gln Gly Xaa Val
1 5 10
<210> 175
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 175
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 176
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 176
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 177
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 177
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 178
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 178
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 179
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 179
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 180
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 180
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 181
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 181
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 182
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 182
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 183
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 183
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 184
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 184
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 185
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 185
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 186
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 186
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 187
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 187
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 188
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 188
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 189
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 189
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 190
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 190
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 191
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 191
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 192
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 192
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 193
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 193
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 194
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 194
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 195
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 195
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 196
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 196
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 197
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 197
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 198
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 198
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 199
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 199
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 200
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 200
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 201
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 201
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 202
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 202
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 203
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 203
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 204
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 204
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 205
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 205
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 206
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 206
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 207
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 207
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 208
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 208
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 209
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 209
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 210
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 210
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 211
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 211
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 212
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 212
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 213
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 213
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 214
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 214
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 215
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 215
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 216
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 216
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 217
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 217
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 218
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 218
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 219
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 219
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 220
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 220
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 221
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 221
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 222
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 222
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 223
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 223
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 224
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 224
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 225
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 225
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 226
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 226
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 227
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 227
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 228
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 228
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 229
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 229
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 230
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 230
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 231
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 231
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 232
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 232
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 233
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 233
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 234
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 234
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 235
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 235
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 236
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 236
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 237
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 237
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 238
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 238
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 239
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 239
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 240
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 240
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 241
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 241
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 242
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 242
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 243
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 243
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 244
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 244
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 245
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 245
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 246
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 246
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 247
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 247
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 248
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 248
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 249
<211> 247
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 249
Met Glu Thr Asp Thr Leu Leu Leu Trp Val Leu Leu Leu Trp Val Pro
1 5 10 15
Gly Ser Thr Gly Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro
20 25 30
Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
35 40 45
Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val
50 55 60
Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp
65 70 75 80
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr
85 90 95
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
100 105 110
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu
115 120 125
Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
130 135 140
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys
145 150 155 160
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
165 170 175
Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser Tyr Lys
180 185 190
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
195 200 205
Lys Leu Thr Val Thr Lys Ser Glu Trp Gln Gln Gly Phe Val Phe Ser
210 215 220
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
225 230 235 240
Leu Ser Leu Ser Pro Gly Lys
245
<210> 250
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 250
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 251
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 251
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 252
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 252
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 253
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 253
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 254
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 254
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly
100 105 110
Ala Gly Thr Thr Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Trp
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 255
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 255
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly
100 105 110
Ala Gly Thr Thr Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Trp
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 256
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 256
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly
100 105 110
Ala Gly Thr Thr Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 257
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 257
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly
100 105 110
Ala Gly Thr Thr Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 258
<211> 213
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 258
Gln Ile Val Leu Ser Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Arg Ala Ser Ser Ser Val Ser Tyr Ile
20 25 30
His Trp Phe Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Val Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Ser Arg Val Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Thr Ser Asn Pro Pro Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 259
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 259
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Asn Tyr Thr Lys Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Gly Ser Ser Pro Trp Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Trp
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 260
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 260
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Asn Tyr Thr Lys Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Gly Ser Ser Pro Trp Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Trp
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 261
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 261
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Asn Tyr Thr Lys Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Gly Ser Ser Pro Trp Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 262
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 262
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Asn Tyr Thr Lys Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Gly Ser Ser Pro Trp Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys Leu Thr Val
405 410 415
Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 263
<211> 213
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 263
Gln Ile Val Met Ser Gln Ser Pro Ala Ile Leu Ser Ala Ser Pro Gly
1 5 10 15
Glu Lys Val Thr Met Thr Cys Arg Ala Arg Ser Ser Val Ser Tyr Ile
20 25 30
His Trp Tyr Gln Gln Lys Pro Gly Ser Ser Pro Lys Pro Trp Ile Tyr
35 40 45
Ala Thr Ser Asn Leu Ala Ser Gly Val Pro Gly Arg Phe Ser Gly Ser
50 55 60
Gly Ser Gly Thr Ser Tyr Ser Leu Thr Ile Thr Arg Val Glu Ala Glu
65 70 75 80
Asp Ala Ala Thr Tyr Tyr Cys Gln Gln Trp Ser Ser Lys Pro Pro Thr
85 90 95
Phe Gly Gly Gly Thr Lys Leu Glu Ile Lys Arg Thr Val Ala Ala Pro
100 105 110
Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly Thr
115 120 125
Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala Lys
130 135 140
Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln Glu
145 150 155 160
Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser Ser
165 170 175
Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr Ala
180 185 190
Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser Phe
195 200 205
Asn Arg Gly Glu Cys
210
<210> 264
<211> 23
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<221> source
<222>
<223> /注释=“人工序列的描述：合成寡核苷酸”
<400> 264
gaatacatac actcctcgtg agg 23
<210> 265
<211> 23
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<221> source
<222>
<223> /注释=“人工序列的描述：合成寡核苷酸”
<400> 265
agaagaatac ttaacatctt tgg 23
<210> 266
<211> 552
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<221> source
<222>
<223> /注释=“人工序列的描述：合成聚核苷酸”
<400> 266
gctcagaact ccgtgatcat cgtggataag aacggccggc tggtgtacct ggtggagaac 60
cctggcggat acgtggctta ctctaaggcc gctaccgtga caggcaagct ggtgcacgcc 120
aacttcggaa ccaagaagga ctttgaggat ctgtacacac cagtgaacgg ctctatcgtg 180
atcgtgcgcg ctggaaagat caccttcgcc gagaaggtgg ctaacgccga gagcctgaac 240
gccatcggcg tgctgatcta catggatcag acaaagtttc ccatcgtgaa cgctgagctg 300
tctttctttg gacacgctca cctgggcacc ggagacccat acacacccgg attccctagc 360
tttaaccaca cccagttccc cccttccagg tctagcggac tgccaaacat ccccgtgcag 420
acaatcagca gagccgctgc cgagaagctg tttggcaaca tggagggaga ctgcccctcc 480
gattggaaga ccgactctac atgtaggatg gtgacctccg agtcaaaaaa tgtcaaactc 540
accgtgtcca at 552
<210> 267
<211> 2329
<212> DNA
<213> 人工序列(Artificial Sequence)
<220>
<221> source
<222>
<223> /注释=“人工序列的描述：合成聚核苷酸”
<400> 267
ctatacagat atataaggat ggggcttttt ttttttaatt tttaaaaaag atttgtttat 60
tattatatgt aagtacactg tagctgtctt cagacactcc agaagagggc atcagatctc 120
attacagatg gttgtgagct accatgtggt cactgggatt tgaactcagg accttcagaa 180
gagcagtcag tgctcttaac tgataagtta ataataagtt aactgataag gtaataaagg 240
tcccctatga aaagggttca gacccaaaga gtcagagatc cacaggttga gaacctcctg 300
ccctaaatct tgttgctctc cttattcaag accactcctg ttgcagttgc tcttaagcat 360
gagtatgctc ccttctgaaa gtctccatag cagccatctc tccagcccca gagtgaggct 420
tttaaaggaa tcttcatgat aaatagaatt tttaaaaaag taactgaagt tacttaaggt 480
gttaaggtac attttattcc ctcagtaact ggttaatcta gcagttttga gtcatacttc 540
atttatcttg actttgaaga gtaagatatt aaaacaattt gcttgatcct tgaagtaagt 600
atttaaatag acattttaat gcagactttt tttagttgac tggtggtgtt gcacgtggtc 660
aatccaagta ctcatgggag gcagaggcag gaggatctct ctctagacca gcctggtcta 720
tagagcaagt tccaggacag ccagggctac acagaaacct tgtttcaaac aagactttta 780
tccttccagg cagctgagcc agaatacata cactcctagg gaagctggtt cacagaagga 840
cgaatccctg gcatactaca tcgagaatca gtttcacgag ttcaagttta gcaaagtctg 900
gagagatgag cactacgtga agatccaggt gaagagctcc gctcagaact ccgtgatcat 960
cgtggataag aacggccggc tggtgtacct ggtggagaac cctggcggat acgtggctta 1020
ctctaaggcc gctaccgtga caggcaagct ggtgcacgcc aacttcggaa ccaagaagga 1080
ctttgaggat ctgtacacac cagtgaacgg ctctatcgtg atcgtgcgcg ctggaaagat 1140
caccttcgcc gagaaggtgg ctaacgccga gagcctgaac gccatcggcg tgctgatcta 1200
catggatcag acaaagtttc ccatcgtgaa cgctgagctg tctttctttg gacacgctca 1260
cctgggcacc ggagacccat acacacccgg attccctagc tttaaccaca cccagttccc 1320
cccttccagg tctagcggac tgccaaacat ccccgtgcag acaatcagca gagccgctgc 1380
cgagaagctg tttggcaaca tggagggaga ctgcccctcc gattggaaga ccgactctac 1440
atgtaggatg gtgacctccg agtcaaaaaa tgtcaaactc accgtgtcca atgtgctgaa 1500
agaacgacgc atcctgaata tctttggagt tattaaaggt tatgaggaac caggtaaaga 1560
cctgctttgt actttttcac tttactgttt tgcttactgt agataggtct agtgcaggaa 1620
ggagaaggat gctagcttgg catgaactgc tatatcttgt ttgtcctaat gtgaactttg 1680
taatatatgt gtatataaca cataatatgg ccatgtaagt gtatggagag gccagagtta 1740
agtattaaat atctttctgt aatcatttaa aattttacat atgaaggtca gtgaacagat 1800
tgaaggagtt ttgtccaggt gggacttgga tctaaatttt ttacaatgcc tggcagcaaa 1860
caccttttta atcaactgag ctgtctcccc aaataaagtg aatgtgatat cagcttgtgg 1920
ataatttttt tttgttgctt tgataagtgg ttttcttaca ggatcacata ccagttctgt 1980
ccatagcatt aaacaaacat aactgtcatg cagtagatta atgtgcaggg cacatccaac 2040
agtcacattt attaatagga caaaaagttg gaccttatat gtagcacacc tataattcca 2100
gtgctaggaa gatccgggta ggagatcctt agttcggtgc tacttagtga gggtttgttt 2160
caaaaaacaa aagctatgat ggtgtgttgc cttttttctt ttagaccgtt atgttgtagt 2220
aggagcccag agagacgctt tgggtgctgg tgttgcggcg aagtccagtg tgggaacagg 2280
tcttctgttg aaacttgccc aagtattctc agatatgatt tcaaaaggt 2329
<210> 268
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 268
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 269
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 269
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 270
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 270
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 271
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 271
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 272
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 272
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 273
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 273
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 274
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 274
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 275
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 275
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 276
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 276
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 277
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 277
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 278
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 278
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 279
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 279
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 280
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 280
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 281
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 281
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 282
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 282
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 283
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 283
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 284
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 284
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 285
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 285
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 286
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 286
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 287
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 287
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 288
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 288
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 289
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 289
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 290
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 290
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 291
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 291
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 292
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 292
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 293
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 293
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 294
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 294
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 295
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 295
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 296
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 296
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 297
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 297
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 298
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 298
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 299
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 299
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 300
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 300
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 301
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 301
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 302
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 302
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 303
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 303
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 304
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 304
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 305
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 305
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 306
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 306
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 307
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 307
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 308
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 308
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 309
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 309
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 310
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 310
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 311
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 311
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 312
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 312
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 313
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 313
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 314
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 314
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 315
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 315
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 316
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 316
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 317
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 317
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 318
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 318
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 319
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 319
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 320
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 320
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 321
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 321
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 322
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 322
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 323
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 323
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 324
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 324
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 325
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 325
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 326
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 326
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 327
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 327
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 328
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 328
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 329
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 329
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 330
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 330
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 331
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 331
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 332
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 332
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 333
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 333
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 334
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 334
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 335
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 335
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 336
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 336
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 337
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 337
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 338
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 338
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 339
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 339
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 340
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 340
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 341
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 341
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Val Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 342
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 342
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 343
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 343
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 344
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 344
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 345
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 345
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 346
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 346
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 347
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 347
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 348
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 348
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 349
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 349
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 350
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 350
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 351
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 351
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 352
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 352
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 353
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 353
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 354
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 354
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 355
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 355
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Leu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 356
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 356
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 357
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 357
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 358
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 358
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 359
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 359
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 360
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 360
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 361
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 361
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 362
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 362
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 363
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 363
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 364
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 364
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 365
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 365
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 366
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 366
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 367
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 367
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 368
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 368
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 369
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 369
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Trp Trp Glu Ser Tyr Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Thr Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 370
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 370
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 371
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 371
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 372
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 372
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 373
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 373
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 374
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 374
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 375
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 375
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 376
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 376
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Ser
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 377
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 377
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 378
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 378
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 379
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 379
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 380
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 380
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 381
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 381
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 382
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 382
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 383
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 383
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ala Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Ser Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 384
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 384
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 385
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 385
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 386
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 386
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 387
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 387
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 388
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 388
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 389
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 389
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 390
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 390
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Phe Gly Thr Glu Trp Ser Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 391
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 391
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 392
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 392
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 393
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 393
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 394
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 394
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 395
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 395
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 396
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 396
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 397
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 397
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 398
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 398
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 399
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 399
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 400
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 400
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 401
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 401
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 402
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 402
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 403
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 403
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 404
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 404
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 405
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 405
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 406
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 406
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 407
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 407
Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 408
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 408
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 409
<211> 217
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 409
Ala Pro Glu Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys
1 5 10 15
Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val
20 25 30
Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr
35 40 45
Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu
50 55 60
Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His
65 70 75 80
Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys
85 90 95
Ala Leu Gly Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln
100 105 110
Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu
115 120 125
Thr Lys Asn Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro
130 135 140
Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn
145 150 155 160
Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu
165 170 175
Val Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val
180 185 190
Phe Ser Cys Ser Val Leu His Glu Ala Leu His Ser His Tyr Thr Gln
195 200 205
Lys Ser Leu Ser Leu Ser Pro Gly Lys
210 215
<210> 410
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 410
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly
100 105 110
Ala Gly Thr Thr Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 411
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 411
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Met Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Asn Met His Trp Val Lys Gln Thr Pro Gly Arg Gly Leu Glu Trp Ile
35 40 45
Gly Ala Ile Tyr Pro Gly Asn Gly Asp Thr Ser Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Ala Asp Lys Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Thr Tyr Tyr Gly Gly Asp Trp Tyr Phe Asn Val Trp Gly
100 105 110
Ala Gly Thr Thr Val Thr Val Ser Ala Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 412
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 412
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Asn Tyr Thr Lys Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Gly Ser Ser Pro Trp Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Leu Leu Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 413
<211> 451
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 413
Gln Val Gln Leu Gln Gln Pro Gly Ala Glu Leu Val Arg Pro Gly Thr
1 5 10 15
Ser Val Lys Leu Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Ser Tyr
20 25 30
Trp Met His Trp Ile Lys Gln Arg Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Val Ile Asp Pro Ser Asp Asn Tyr Thr Lys Tyr Asn Gln Lys Phe
50 55 60
Lys Gly Lys Ala Thr Leu Thr Val Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Met Gln Leu Ser Ser Leu Thr Ser Glu Asp Ser Ala Val Tyr Phe Cys
85 90 95
Ala Arg Glu Gly Tyr Tyr Gly Ser Ser Pro Trp Phe Ala Tyr Trp Gly
100 105 110
Gln Gly Thr Leu Val Thr Val Ser Ser Ala Ser Thr Lys Gly Pro Ser
115 120 125
Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly Gly Thr Ala
130 135 140
Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro Val Thr Val
145 150 155 160
Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr Phe Pro Ala
165 170 175
Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val Val Thr Val
180 185 190
Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn Val Asn His
195 200 205
Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro Lys Ser Cys
210 215 220
Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu Ala Ala Gly
225 230 235 240
Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp Thr Leu Met
245 250 255
Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp Val Ser His
260 265 270
Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly Val Glu Val
275 280 285
His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn Ser Thr Tyr
290 295 300
Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp Leu Asn Gly
305 310 315 320
Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro Ala Pro Ile
325 330 335
Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu Pro Gln Val
340 345 350
Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn Gln Val Ser
355 360 365
Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile Ala Val Glu
370 375 380
Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn Tyr Lys Thr Thr Pro Pro
385 390 395 400
Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys Leu Thr Val
405 410 415
Thr Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys Ser Val Met
420 425 430
His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu Ser Leu Ser
435 440 445
Pro Gly Lys
450
<210> 414
<211> 7
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<220>
<221> MOD_RES
<222> (2)..(2)
<223> 氨基酸
<400> 414
Tyr Xaa Thr Glu Trp Ser Ser
1 5
<210> 415
<211> 9
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成肽”
<220>
<221> MOD_RES
<222> (2)..(3)
<223> 氨基酸
<220>
<221> MOD_RES
<222> (5)..(8)
<223> 氨基酸
<400> 415
Thr Xaa Xaa Glu Xaa Xaa Xaa Xaa Phe
1 5
<210> 416
<211> 454
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 416
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Phe Asp Gly Thr Lys Lys Tyr Tyr Thr Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Ile Gly Ala Arg Arg Gly Pro Tyr Tyr Met Asp
100 105 110
Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
130 135 140
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
195 200 205
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
355 360 365
Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
405 410 415
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Pro Gly Lys
450
<210> 417
<211> 454
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 417
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Phe Asp Gly Thr Lys Lys Tyr Tyr Thr Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Ile Gly Ala Arg Arg Gly Pro Tyr Tyr Met Asp
100 105 110
Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
130 135 140
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
195 200 205
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
355 360 365
Gln Val Ser Leu Trp Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Tyr Gly Thr Glu Trp Ser Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser Lys
405 410 415
Leu Thr Val Ser Lys Glu Glu Trp Gln Gln Gly Phe Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Pro Gly Lys
450
<210> 418
<211> 454
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 418
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Phe Asp Gly Thr Lys Lys Tyr Tyr Thr Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Ile Gly Ala Arg Arg Gly Pro Tyr Tyr Met Asp
100 105 110
Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
130 135 140
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
195 200 205
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Ala Ala Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
355 360 365
Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys
405 410 415
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Pro Gly Lys
450
<210> 419
<211> 454
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 419
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Pro Gly Arg
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Ala Phe Ser Ser Tyr
20 25 30
Gly Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ala Val Ile Trp Phe Asp Gly Thr Lys Lys Tyr Tyr Thr Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Thr Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Arg Gly Ile Gly Ala Arg Arg Gly Pro Tyr Tyr Met Asp
100 105 110
Val Trp Gly Lys Gly Thr Thr Val Thr Val Ser Ser Ala Ser Thr Lys
115 120 125
Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys Ser Thr Ser Gly
130 135 140
Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr Phe Pro Glu Pro
145 150 155 160
Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser Gly Val His Thr
165 170 175
Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser Leu Ser Ser Val
180 185 190
Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr Tyr Ile Cys Asn
195 200 205
Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys Lys Val Glu Pro
210 215 220
Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys Pro Ala Pro Glu
225 230 235 240
Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys Asp
245 250 255
Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val Asp
260 265 270
Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp Tyr Val Asp Gly
275 280 285
Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Tyr Asn
290 295 300
Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp Trp
305 310 315 320
Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Ala Leu Pro
325 330 335
Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg Glu
340 345 350
Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu Leu Thr Lys Asn
355 360 365
Gln Val Ser Leu Ser Cys Ala Val Lys Gly Phe Tyr Pro Ser Asp Ile
370 375 380
Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys Thr
385 390 395 400
Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Val Ser Lys
405 410 415
Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn Val Phe Ser Cys
420 425 430
Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser Leu
435 440 445
Ser Leu Ser Pro Gly Lys
450
<210> 420
<211> 214
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成多肽”
<400> 420
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Ser Ile Ser Ser Tyr
20 25 30
Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Ala Ala Ser Ser Leu Gln Ser Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Ser Tyr Ser Thr Pro Leu
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg Thr Val Ala Ala
100 105 110
Pro Ser Val Phe Ile Phe Pro Pro Ser Asp Glu Gln Leu Lys Ser Gly
115 120 125
Thr Ala Ser Val Val Cys Leu Leu Asn Asn Phe Tyr Pro Arg Glu Ala
130 135 140
Lys Val Gln Trp Lys Val Asp Asn Ala Leu Gln Ser Gly Asn Ser Gln
145 150 155 160
Glu Ser Val Thr Glu Gln Asp Ser Lys Asp Ser Thr Tyr Ser Leu Ser
165 170 175
Ser Thr Leu Thr Leu Ser Lys Ala Asp Tyr Glu Lys His Lys Val Tyr
180 185 190
Ala Cys Glu Val Thr His Gln Gly Leu Ser Ser Pro Val Thr Lys Ser
195 200 205
Phe Asn Arg Gly Glu Cys
210
<210> 421
<211> 6
<212> PRT
<213> 人工序列(Artificial Sequence)
<220>
<221> SITE
<222>
<223> /注释=“人工序列的描述：合成6xHis标签”
<400> 421
His His His His His His
1 5
Claims (92)
1.一种被修饰的Fc多肽二聚体，或其二聚体片段，所述被修饰的Fc多肽二聚体，或其二聚体片段：
(a)特异性结合TfR；
(b)能够结合Fcγ受体(FcγR)；并且
(c)不大体上消耗体内网织红细胞。
2.一种被修饰的Fc多肽二聚体，或其二聚体片段，所述被修饰的Fc多肽二聚体，或其二聚体片段包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含(i)TfR结合位点以及(ii)当结合于TfR时减少FcγR结合的一个或多个氨基酸修饰；以及
(b)第二Fc多肽，所述第二Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰。
3.如权利要求1或2所述的被修饰的Fc多肽二聚体，其中所述TfR结合位点包含被修饰的CH3结构域。
4.如权利要求3所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域衍生自人IgG1、IgG2、IgG3或IgG4 CH3结构域。
5.如权利要求3或4所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含在包含384、386、387、388、389、390、413、416以及421的根据EU编号的氨基酸位置集合中的五个、六个、七个、八个或九个取代。
6.如权利要求5所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在包含380、391、392以及415的位置的一个、两个、三个或四个取代。
7.如权利要求5或6所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在包含414、424以及426的位置的一个、两个或三个取代。
8.如权利要求1至7中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的Fc多肽二聚体结合于TfR的顶端结构域。
9.如权利要求8所述的被修饰的Fc多肽二聚体，其中所述被修饰的Fc多肽二聚体结合于TfR，而不抑制转铁蛋白与TfR的结合。
10.如权利要求8或9所述的被修饰的Fc多肽二聚体，其中所述被修饰的Fc多肽二聚体结合于包含TfR的氨基酸208的表位。
11.如权利要求5至10中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含在位置388的Trp。
12.如权利要求5至11中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含在位置421的芳族氨基酸。
13.如权利要求12所述的被修饰的Fc多肽二聚体，其中在位置421的所述芳族氨基酸为Trp或Phe。
14.如权利要求5至10中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含至少一个选自以下的位置：位置384为Leu、Tyr、Met或Val；位置386为Leu、Thr、His或Pro；位置387为Val、Pro或酸性氨基酸；位置388为Trp；位置389为Val、Ser或Ala；位置413为Glu、Ala、Ser、Leu、Thr或Pro；位置416为Thr或酸性氨基酸；以及位置421为Trp、Tyr、His或Phe。
15.如权利要求14所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含选自以下的两个、三个、四个、五个、六个、七个或八个位置：位置384为Leu、Tyr、Met或Val；位置386为Leu、Thr、His或Pro；位置387为Val、Pro或酸性氨基酸；位置388为Trp；位置389为Val、Ser或Ala；位置413为Glu、Ala、Ser、Leu、Thr或Pro；位置416为Thr或酸性氨基酸；以及位置421为Trp、Tyr、His或Phe。
16.如权利要求5至15中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含在位置384的Leu或Met；在位置386的Leu、His或Pro；在位置387的Val；在位置388的Trp；在位置389的Val或Ala；在位置413的Pro；在位置416的Thr；和/或在位置421的Trp。
17.如权利要求16所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置391的Ser、Thr、Gln或Phe。
18.如权利要求16或17所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置380的Trp、Tyr、Leu或Gln。
19.如权利要求16至18中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置392的Gln、Phe或His。
20.如权利要求16或17所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置380的Trp和/或在位置392的Gln。
21.如权利要求14至20中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含选自以下的一个、两个或三个位置：位置414为Lys、Arg、Gly或Pro；位置424为Ser、Thr、Glu或Lys；以及位置426为Ser、Trp或Gly。
22.如权利要求5至15中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含在位置384的Tyr、在位置386的Thr、在位置387的Glu或Val、在位置388的Trp、在位置389的Ser、在位置413的Ser或Thr、在位置416的Glu和/或在位置421的Phe。
23.如权利要求22所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置380的Trp、Tyr、Leu或Gln。
24.如权利要求22或23所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置415的Glu。
25.如权利要求22所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含在位置380的Trp和/或在位置415的Glu。
26.如权利要求22至25中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含在位置390的Asn。
27.如权利要求6至10中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含以下取代中的一者或多者：在位置380的Trp；在位置386的Thr；在位置388的Trp；在位置389的Val；在位置413的Ser或Thr；在位置415的Glu；和/或在位置421的Phe。
28.如权利要求5至27中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域与SEQ ID NO:4-29和64-127中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。
29.如权利要求28所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域与SEQID NO:66、68、94、107-109、119以及268-270中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。
30.如权利要求5至27中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域与SEQ ID NO:1的氨基酸111-217具有至少85％同一性，前提条件为所述同一性百分比不包括根据EU编号的位置384、386、387、388、389、390、413、416以及421的集合。
31.如权利要求5至30中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含SEQ ID NO:4-29和125-127中的任一者的氨基酸154-160和/或183-191。
32.如权利要求6至10中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含至少一个选自以下的位置：位置380为Trp、Leu或Glu；位置384为Tyr或Phe；位置386为Thr；位置387为Glu；位置388为Trp；位置389为Ser、Ala、Val或Asn；位置390为Ser或Asn；位置413为Thr或Ser；位置415为Glu或Ser；位置416为Glu；以及位置421为Phe。
33.如权利要求32所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含选自以下的2个、3个、4个、5个、6个、7个、8个、9个、10个或11个位置：位置380为Trp、Leu或Glu；位置384为Tyr或Phe；位置386为Thr；位置387为Glu；位置388为Trp；位置389为Ser、Ala、Val或Asn；位置390为Ser或Asn；位置413为Thr或Ser；位置415为Glu或Ser；位置416为Glu；以及位置421为Phe。
34.如权利要求33所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含如下11个位置：位置380为Trp、Leu或Glu；位置384为Tyr或Phe；位置386为Thr；位置387为Glu；位置388为Trp；位置389为Ser、Ala、Val或Asn；位置390为Ser或Asn；位置413为Thr或Ser；位置415为Glu或Ser；位置416为Glu；以及位置421为Phe。
35.如权利要求33或34所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域与SEQ ID NO:4-29和64-127中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。
36.如权利要求35所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域与SEQID NO:66、68、94、107-109、119以及268-270中的任一者的氨基酸111-217具有至少85％同一性、至少90％同一性或至少95％同一性。
37.如权利要求35所述的被修饰的Fc多肽二聚体，其中在根据EU编号方案对应于位置380、384、386、384、388、389、390、391、392、413、414、415、416、421、424以及426的位置中的至少5者、6者、7者、8者、9者、10者、11者、12者、13者、14者、15者或16者处的残基未发生缺失或取代。
38.如权利要求3所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域包含SEQID NO:38-61和131-173中的任一者的序列。
39.如权利要求5至37中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的CH3结构域还包含根据EU编号方案(i)在位置366的Trp或者(ii)在位置366的Ser、在位置368的Ala以及在位置407的Val。
40.如权利要求5至39中任一项所述的被修饰的Fc多肽二聚体，其中对应未被修饰的CH3结构域为人IgG1、IgG2、IgG3或IgG4 CH3结构域。
41.如权利要求2至40中任一项所述的被修饰的Fc多肽二聚体，其中所述当结合于TfR时减少FcγR结合的氨基酸修饰包含根据EU编号方案在位置234和在位置235的Ala。
42.如权利要求2至41中任一项所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽和/或所述第二Fc多肽包含增加血清半衰期的氨基酸修饰。
43.如权利要求42所述的被修饰的Fc多肽二聚体，其中所述增加血清半衰期的氨基酸修饰包含根据EU编号方案(i)在位置428的Leu和在位置434的Ser，或者(ii)在位置434的Ser或Ala。
44.如权利要求1至43中任一项所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽和/或所述第二Fc多肽进一步融合至Fab。
45.如权利要求2至44中任一项所述的被修饰的Fc多肽二聚体，其中根据EU编号方案，所述第一Fc多肽包含杵突变T366W并且所述第二Fc多肽包含臼突变T366S、L368A以及Y407V。
46.如权利要求2至44中任一项所述的被修饰的Fc多肽二聚体，其中根据EU编号方案，所述第一Fc多肽包含臼突变T366S、L368A以及Y407V并且所述第二Fc多肽包含杵突变T366W。
47.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
48.如权利要求47所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:178、190、202、214、226、238、252、286、298以及310中的任一者的序列。
49.如权利要求47或48所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:397的序列。
50.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V，并且不含TfR结合位点或减少FcγR结合的任何修饰。
51.如权利要求50所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:323、330、337、344、351、358、365、372、379以及386中的任一者的序列。
52.如权利要求50或51所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:397的序列。
53.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及杵突变T366W，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
54.如权利要求53所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:178、190、202、214、226、238、252、286、298以及310中的任一者的序列。
55.如权利要求53或54所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:407的序列。
56.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A、杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的臼突变T366S、L368A以及Y407V以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
57.如权利要求56所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:323、330、337、344、351、358、365、372、379以及386中的任一者的序列。
58.如权利要求56或57所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:407的序列。
59.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
60.如权利要求59所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:184、196、208、220、232、244、280、292、304以及316中的任一者的序列。
61.如权利要求59或60所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:391的序列。
62.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W，并且不含TfR结合位点或减少FcγR结合的任何修饰。
63.如权利要求62所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:326、333、340、347、354、361、368、375、382以及389中的任一者的序列。
64.如权利要求62或63所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:391的序列。
65.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点、根据EU编号方案的氨基酸修饰L234A和L235A以及臼突变T366S、L368A以及Y407V，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
66.如权利要求65所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:184、196、208、220、232、244、280、292、304以及316中的任一者的序列。
67.如权利要求65或66所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:404的序列。
68.一种被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含：
(a)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点；根据EU编号方案的氨基酸修饰L234A和L235A；臼突变T366S、L368A以及Y407V；以及氨基酸修饰N434S加上或不加上M428L，以及
(b)第二Fc多肽，所述第二Fc多肽包含根据EU编号方案的杵突变T366W以及氨基酸修饰N434S加上或不加上M428L，并且不含TfR结合位点或减少FcγR结合的任何修饰。
69.如权利要求68所述的被修饰的Fc多肽二聚体，其中所述第一Fc多肽包含SEQ IDNO:326、333、340、347、354、361、368、375、382以及389中的任一者的序列。
70.如权利要求68或69所述的被修饰的Fc多肽二聚体，其中所述第二Fc多肽包含SEQID NO:404的序列。
71.如权利要求1至70中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的Fc多肽二聚体不大体上消耗网织红细胞。
72.如权利要求71所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后消耗的网织红细胞的量小于在施用对照之后消耗的网织红细胞的量。
73.如权利要求72所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后消耗的网织红细胞的量小于在施用对照之后消耗的网织红细胞的量的50％、45％、40％、35％、30％、25％、20％、15％、10％、8％、5％、3％、2％或1％。
74.如权利要求71所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后剩余的网织红细胞的量大于在施用对照之后剩余的网织红细胞的量。
75.如权利要求74所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后剩余的网织红细胞的量比在施用对照之后剩余的网织红细胞的量大至少1％、5％、10％、15％、20％、25％、30％、35％、40％、45％或50％。
76.如权利要求1至70中任一项所述的被修饰的Fc多肽二聚体，其中所述被修饰的Fc多肽二聚体不大体上消耗骨髓中的网织红细胞。
77.如权利要求76所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后所述骨髓中消耗的网织红细胞的量小于在施用对照之后所述骨髓中消耗的网织红细胞的量。
78.如权利要求77所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后所述骨髓中消耗的网织红细胞的量小于在施用对照之后所述骨髓中消耗的网织红细胞的量的50％、45％、40％、35％、30％、25％、20％、15％、10％、8％、5％、3％、2％或1％。
79.如权利要求76所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后所述骨髓中剩余的网织红细胞的量大于在施用对照之后所述骨髓中剩余的网织红细胞的量。
80.如权利要求79所述的被修饰的Fc多肽二聚体，其中在施用所述被修饰的Fc多肽二聚体之后所述骨髓中剩余的网织红细胞的量比在施用对照之后所述骨髓中剩余的网织红细胞的量大至少1％、5％、10％、15％、20％、25％、30％、35％、40％、45％或50％。
81.如权利要求72至75以及77至80中任一项所述的被修饰的Fc多肽二聚体，其中所述对照为具有完全效应功能和/或不含减少FcγR结合的突变的对应TfR结合性Fc二聚体。
82.一种Fc多肽二聚体-Fab融合蛋白，所述Fc多肽二聚体-Fab融合蛋白能够主动转运穿过BBB，所述Fc多肽二聚体-Fab融合蛋白包含：
(a)抗体可变区，所述抗体可变区能够结合抗原，或其抗原结合片段；以及
(b)被修饰的Fc多肽二聚体，所述被修饰的Fc多肽二聚体包含(i)特异性结合TfR的第一Fc多肽，所述第一Fc多肽包含TfR结合位点以及当结合于TfR时减少FcγR结合的一个或多个氨基酸修饰，以及(ii)第二Fc多肽，所述第二Fc多肽不含TfR结合位点或减少FcγR结合的任何修饰。
83.如权利要求82所述的Fc多肽二聚体-Fab融合蛋白，其中所述当结合于TfR时减少FcγR结合的氨基酸修饰包含根据EU编号方案在位置234和在位置235的Ala。
84.如权利要求82或83所述的Fc多肽二聚体-Fab融合蛋白，其中所述第一Fc多肽和/或所述第二Fc多肽包含增加血清半衰期的氨基酸修饰。
85.如权利要求84所述的Fc多肽二聚体-Fab融合蛋白，其中所述增加血清半衰期的氨基酸修饰包含根据EU编号方案(i)在位置428的Leu和在位置434的Ser，或者(ii)在位置434的Ser或Ala。
86.如权利要求82至85中任一项所述的Fc多肽二聚体-Fab融合蛋白，其中抗体可变区序列包含Fab结构域。
87.如权利要求82至86中任一项所述的Fc多肽二聚体-Fab融合蛋白，其中所述抗体可变区序列包含两条抗体可变区重链和两条抗体可变区轻链，或它们各自的片段。
88.一种药物组合物，所述药物组合物包含如权利要求1至81中任一项所述的被修饰的Fc多肽二聚体和药学上可接受的载剂。
89.一种药物组合物，所述药物组合物包含如权利要求82至87中任一项所述的Fc多肽二聚体-Fab融合蛋白和药学上可接受的载剂。
90.一种将组合物胞吞转送穿过内皮的方法，所述方法包括使所述内皮与包含如权利要求1至81中任一项所述的被修饰的Fc多肽二聚体的组合物接触。
91.一种将组合物胞吞转送穿过内皮的方法，所述方法包括使所述内皮与包含如权利要求82至87中任一项所述的Fc多肽二聚体-Fab融合蛋白的组合物接触。
92.如权利要求90或91所述的方法，其中所述内皮为BBB。
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| JP2021510162A (ja) | 2021-04-15 |
| MX2020007389A (es) | 2020-10-14 |
| IL275969A (en) | 2020-08-31 |
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| AU2019207735A1 (en) | 2020-07-23 |
| BR112020013921A2 (pt) | 2020-12-01 |
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| CA3088157A1 (en) | 2019-07-18 |
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| KR20200119251A (ko) | 2020-10-19 |
| US20210130485A1 (en) | 2021-05-06 |
| TW201934573A (zh) | 2019-09-01 |
| SG11202006420TA (en) | 2020-08-28 |
| EP3737701A1 (en) | 2020-11-18 |
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