CN110526971B - 抗-CD38抗体和与致弱干扰素α-2B的融合体 - Google Patents
抗-CD38抗体和与致弱干扰素α-2B的融合体 Download PDFInfo
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Abstract
提供了特异地结合CD38的抗体，以及包括融合到致弱干扰素α‑2B蛋白质上的这样的抗体结构。抗‑CD38‑致弱干扰素α‑2b融合结构可以用于抑制表达CD38和IFN‑α2b受体的癌症细胞的增殖，以及诱导这样的细胞凋亡。抑制癌症细胞增殖和诱导癌症细胞凋亡可以充当治疗潜在癌症的基础。
Description
序列表参考
本申请包括电子方式提交的序列表，其作为名称为抗-CD38_抗体_ST25的文本文件，创建于2013年4月29日，大小为462,000字节。该序列表通过援引并入本文。
技术领域
本公开大体上涉及抗体工程领域。更具体地说，本发明涉及特异地结合CD38的抗体，以及包括这样的抗体和致弱干扰素-α配体(attenuated interferon-alpha ligands)的结构，和使用这些结构的治疗方法。在这些结构中，该抗体指导该配体到表达CD38和该配体的受体的细胞，并且该致弱干扰素-α降低不表达CD38的细胞中的干扰素信号。
背景技术
贯穿整个说明书，引用了各种公开物，包括专利，公开的申请，技术文章，学术文章，和基因或蛋白质的访问号(gene or protein accession numbers)。每个这些材料以其全部为任何目的在此通过援引并入本文。
CD38是46kDa II类跨膜糖蛋白。它具有20个氨基酸的短N-端胞浆区(N-terminalcytoplasmic tail)、单个跨膜螺旋和256个氨基酸的长胞外域。它被表达在许多免疫细胞表面和相当比例的正常骨髓前体细胞上，该免疫细胞包括CD4和CD8阳性T细胞、B细胞、NK细胞、单核细胞、浆细胞(plasma cells)。在有些情况下，淋巴细胞中CD38的表达可能依赖于细胞的分化和激活状态，例如，对CD38表达来说，休眠T和B细胞可呈阴性，而不成熟的和激活的淋巴细胞可明显地呈阳性。已经在非造血器官中检测到CD38 mRNA表达，比如胰脏、大脑、脾脏和肝脏(Koguma,T.(1994)Biochim.Biophys.Acta 1223:160)。
CD38是参与跨膜信号和细胞粘附的多能胞外酶。它还被公知为循环ADP核糖水解酶，因为它能依赖细胞外pH将NAD+和NADP+转化成cADPR、ADPR和NAADP。这些产物诱导细胞内的Ca2+-动员(Ca2+-mobilization)，这会导致酪氨酸磷酸化和细胞激活。CD38也是能与配体CD31相互作用的受体。通过CD31的受体激活导致细胞内事件，包括Ca2+-动员、细胞激活、增殖、分化和迁移。
在T-和B-系急性淋巴细胞性白血病(T-and B-lineage acute lymphoblasticleukemias)、一些急性髓细胞性白血病(acute myelocyticleukemias)、滤泡性中心细胞性淋巴瘤(follicular center cell lymphomas)和T淋巴细胞性淋巴瘤的大多数情况下，CD38在多发性骨髓瘤细胞上被高水平表达。CD38还被表达在B-系慢性淋巴细胞性白血病(B-CLL)细胞上。在一些情况下，具有CD38+克隆的B-CLL病人的特点是不顺利的较高阶段疾病的临床病程，对化学治疗反应性差以及生存时间短。已经提议使用针对CD38的抗体治疗CD38-表达癌症和恶性血液病。因此，提供具有想要的制造、稳定性和免疫原性属性的供选择的针对CD38的抗体可能是有利的。
已经描述了许多肽和多肽类配体通过与细胞表面的受体相互作用发挥其功能，由此刺激、抑制或另外调节生物应答，通常涉及具有所述受体的细胞内的信号传导通路。这样的配体的实施例包括肽和多肽类激素、细胞因子、趋化因子、生长因子和促细胞凋亡因子。
由于这样的配体的生物活性，许多具有作为治疗剂的潜在用途。几个肽或多肽类配体已经被管理机构批准作为治疗产品，其包括，例如，人生长激素、胰岛素、干扰素(IFN)-α2b、IFN-α2a、IFNβ、红细胞生成素、G-CSF和GM-CSF。
虽然这些和其他配体已经证明在治疗应用中有潜能，但当向人类病人给予时它们也显示出毒性。毒性的一个原因是大多数这些配体引发各种细胞上的受体，包括除介导想要的治疗效果的那些细胞以外的细胞。配体的这样的“脱靶(off target)”活性的后果是许多配体当前不适合用作治疗试剂，因为该配体不能以足够高的剂量给药以在介导治疗效果的靶细胞上产生最大或最佳治疗效果。
例如，从1980年代中期已经知道干扰素，尤其是，IFN-α能够增加细胞凋亡并且减少某些癌细胞的增殖。已经被FDA批准的IFN-α用于治疗几种癌症，包括黑色素瘤、肾细胞癌、B细胞淋巴瘤、多发性骨髓瘤、慢性骨髓性白血病(chronic myelogenous leukemia)(CML)和毛细胞白血病。IFN-α对肿瘤细胞的直接效果是通过IFN-α直接结合这些细胞上的I类IFN受体并且刺激细胞凋亡、最终分化或降低的增殖所介导。IFN-α对非肿瘤细胞的进一步间接效果是刺激免疫系统，这可以通过引起免疫系统抵制肿瘤产生额外的抗癌效果。
这些生物活性由癌细胞表面上的I类干扰素受体介导，当被刺激时，该受体启动导致增殖减少和/或诱导最终分化或细胞凋亡的各种信号传导通路。但是该I类干扰素受体也出现在大多数非癌细胞上。由IFN-α在非癌细胞上激活该受体引起大量促炎性细胞因子和趋化因子的表达，导致毒性和不良反应。这样的毒性可引起严重的类似感冒的症状，这阻止了将IFN-α以对癌细胞发挥最大抗增殖和促凋亡活性的水平向个体配量。
当IFN-α2b被用于治疗多发性骨髓瘤时，其效用至少部分在于它结合到骨髓瘤细胞上的I类干扰素受体上，其反过来引发细胞凋亡和/或增殖降低，因此限制疾病进程。
不幸的是，但是这个IFN还结合到体内的健康细胞上，引发各种其它细胞反应，有些反应是有害的。
Ozzello的公开物(Breast Cancer Research and Treatment 25:265-76,1993)描述了将人IFN-α化学偶联到肿瘤-靶向抗体，由此将IFN-α的直接抑制活性定位到肿瘤，作为降低IFN-α肿瘤生长速率的方法，并且证明了这样的偶联物在人类癌症的异种移植模型中具有抗肿瘤活性。观察到的抗癌活性的机理归因于IFN-α对肿瘤细胞的直接效果，因为实验中使用的人IFN-α没有明显地与鼠I类IFN受体相互作用，这会导致间接抗肿瘤效果。因为没有将人IFN-α结合到鼠细胞上，没有评估抗体-IFN-α偶联物相对于游离IFN-α的毒性。
抗体和IFN-α也可以以融合蛋白的形式连接到一起。例如，WO 01/97844描述了人IFN-α直接融合到对肿瘤抗原CD20特异的IgG的重链C-端上。
通常，IFN可被靶向癌细胞。虽然这种方法可导致IFN针对癌细胞活性的增加，但是它没有完全解决IFN对健康细胞的不想要的活性问题。将IFN-α融合到IgG的重链C端上可以延长IFN-α的半衰期，导致不想要的不利事件。因此需要减小基于配体的药物的脱靶活性，同时保持这样的配体的“靶向(on-target)”治疗效果。
发明内容
本公开的特载新的抗-CD38抗体和包括抗-CD38抗体和致弱IFN-α的结构。包括它们重链和/轻链可变区的一个或多个突变的该抗体保持特异结合CD38的能力，包括在细胞表面上表达的CD38。该抗体可以融合到，例如，致弱形式的干扰素α以形成抗-CD38抗体-致弱干扰素融合结构。
在一些方面，特异地结合CD38的分离的抗体包括包括氨基酸序列SEQ ID NO:559的重链可变区，和包括氨基酸序列SEQ ID NO:664的轻链可变区。在一些方面，特异地结合CD38的分离的抗体包括包括氨基酸序列SEQ ID NO:665的重链可变区，和包括氨基酸序列SEQ ID NO:666的轻链可变区。在一些方面，特异结合到CD38的分离的抗体包括包括氨基酸序列SEQ ID NO:739的重链可变区，和包括氨基酸序列SEQ ID NO:664的轻链可变区。该重链可变区氨基酸序列SEQ ID NO:559排除氨基酸序列SEQ ID NO:13。该轻链可变区氨基酸序列SEQ ID NO:664排除氨基酸序列SEQ ID NO:14。在一些方面，特异地结合CD38的分离的抗体包括包括氨基酸序列SEQ ID NO:200、SEQ ID NO:514或SEQ ID NO:697的重链CDR1，包括氨基酸序列SEQ ID NO:202、SEQ ID NO:516、SEQ ID NO:544、SEQ ID NO:698或SEQ IDNO:737的重链CDR2和包括氨基酸序列SEQ ID NO:204、SEQ ID NO:222、SEQ ID NO:518、SEQID NO:534、SEQ ID NO:535、SEQ ID NO:536、SEQ ID NO:699或SEQ ID NO:738的重链CDR3，并且可进一步包括包括氨基酸序列SEQ ID NO:233、SEQ ID NO:319、SEQ ID NO:583、SEQID NO:590或SEQ ID NO:696的轻链CDR1，包括氨基酸序列SEQ ID NO:235、SEQ ID NO:307、SEQ ID NO:311、SEQ ID NO:585、SEQ ID NO:591或SEQ ID NO:605的轻链CDR2，包括氨基酸序列SEQ ID NO:237、SEQ ID NO:321、SEQ ID NO:324、SEQ ID NO:587或SEQ ID NO:594的轻链CDR3。
在优选的方面，该重链可变区包括氨基酸序列SEQ ID NO:34、SEQ ID NO:18、SEQID NO:665、SEQ ID NO:165、SEQ ID NO:166、SEQ ID NO:167、SEQ ID NO:179、SEQ ID NO:180、SEQ ID NO:156、SEQ ID NO:197、SEQ ID NO:152、SEQ ID NO:720、SEQ ID NO:721、SEQID NO:722、SEQ ID NO:723、SEQ ID NO:739、SEQ ID NO:740、SEQ ID NO:741、SEQ ID NO:742、SEQ ID NO:728、SEQ ID NO:730、SEQ ID NO:731。在优选的方面，该轻链可变区包括氨基酸序列SEQ ID NO:65、SEQ ID NO:68、SEQ ID NO:86、SEQ ID NO:88、SEQ ID NO:92、SEQID NO:93、SEQ ID NO:660、SEQ ID NO:661、SEQ ID NO:662、SEQ ID NO:663、SEQ ID NO:161、SEQ ID NO:184、SEQ ID NO:185、SEQ ID NO:188、SEQ ID NO:198或SEQ ID NO:700、SEQ ID NO:701、SEQ ID NO:704、SEQ ID NO:705、SEQ ID NO:706、SEQ ID NO:707、SEQ IDNO:708、SEQ ID NO:709、SEQ ID NO:710、SEQ ID NO:711。
该抗体优选能够结合到CD38阳性细胞上，该抗体可结合到CD38阳性细胞上，具有EC50值小于约100nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约75nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约50nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约30nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约25nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约20nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约15nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约13nM。该抗体可结合到CD38阳性细胞上，具有EC50值小于约10nM。
该抗体可以是单克隆抗体，优选地是全人抗体。该坑体可以包括FAb。该抗体可包括人IgGl恒定区或人lgG4恒定区。该lgGl或lgG4恒定区可以包括根据EU编号体系(EUnumbering system)在位置252处的酪氨酸，在位置254处的苏氨酸和在位置256处的谷氨酸。该lgG4恒定区可以包括根据EU编号体系在位置228处的脯氨酸，并且在位置228处的脯氨酸可以为在位置252处的酪氨酸、在位置254处的苏氨酸和在位置256处的谷氨酸的附加。
在一些方面，该抗体被融合到致弱干扰素α-2b上。干扰素α-2b可以包括位置145处的丙氨酸被甘氨酸或天冬氨酸取代，包括具有氨基酸序列SEQ.ID NO:649或SEQ ID NO:651的干扰素α-2b。该致弱干扰素α-2b可以直接融合到IgGl或lgG4恒定区的C-端，并且该抗体可以包括氨基酸序列SEQ ID NO:9、SEQ ID NO:10、SEQ ID NO:652、SEQ ID NO:653、SEQ IDNO:654、SEQ ID NO:655、SEQ ID NO:656、SEQ ID NO:657、SEQ ID NO:658或SEQ ID NO:694。该抗体，包括融合致弱干扰素α-2b的抗体，可以被包括在包含药学上可接受的载体的组合物中。
提供了编码该抗体的分离的多核苷酸和融合到致弱干扰素α-2b上的抗体。该多核苷酸可包括核酸序列SEQ ID NO:667、SEQ ID NO:670、SEQ ID NO:671、SEQ ID NO:672、SEQID NO:673、SEQ ID NO:674、SEQ ID NO:668、SEQ ID NO:669、SEQ ID NO:675、SEQ ID NO:676或SEQ ID NO:677、SEQ ID NO:678、SEQ ID NO:679、SEQ ID NO:680、SEQ ID NO:681、SEQ ID NO:682、SEQ ID NO:683、SEQ ID NO:684、SEQ ID NO:685、SEQ ID NO:686、SEQ IDNO:687、SEQ ID NO:688、SEQ ID NO:689、SEQ ID NO:690、SEQ ID NO:691、SEQ ID NO:692、SEQ ID NO:693、SEQ ID NO:695、SEQ ID NO:702、SEQ ID NO:703、SEQ ID NO:712、SEQ IDNO:713、SEQ ID NO:714、SEQ ID NO:715、SEQ ID NO:716、SEQ ID NO:717、SEQ ID NO:718、SEQ ID NO:719、SEQ ID NO:724、SEQ ID NO:725、SEQ ID NO:726、SEQ ID NO:727、SEQ IDNO:732、SEQ ID NO:733、SEQ ID NO:734、SEQ ID NO:735、SEQ ID NO:743、SEQ ID NO:744、SEQ ID NO:745、SEQ ID NO:746。该多核苷酸可以包括载体。该载体可以被用于，例如，转化细胞。还提供了包以括这样的多核苷酸的转化细胞。该转化细胞可以包括哺乳动物细胞、酵母细胞或昆虫细胞。
还提供了表达该抗体的稳定细胞。抗体表达细胞可以是哺乳动物细胞。优选的细胞是中国仓鼠卵巢(Chinese Hamster Ovary)(CHO)细胞。
提供了包括融合到致弱干扰素α-2b上的抗体的试剂盒。该试剂盒包括该抗-CD38-致弱干扰素α-2b融合结构，和在抑制在它的表面表达CD38和干扰素α-2b受体的肿瘤细胞的增殖的方法中使用该结构的说明书，在诱导在它的表面表达CD38和干扰素α-2b受体的肿瘤细胞的凋亡的方法中使用该结构的说明书，在治疗需要它们的个体中的包括在它们的表面表达CD38和干扰素α-2b受体的细胞的肿瘤的方法中使用该结构的说明书，和可选择地，药学上可接受的载体。提供了包括抗CD38-抗体的试剂盒，这样的试剂盒包括该抗CD38-抗体和在检测从个体分离的组织标本中CD38-阳性肿瘤细胞的方法中使用该抗体的说明书，该抗体可以可选择地被融合到致弱干扰素α-2b蛋白质上。
抗-CD38抗体-致弱干扰素α-2b融合结构在包括在它们的表面表达CD38和干扰素α-2b受体的细胞的肿瘤的治疗中可以用作治疗剂。通常情况下，治疗方法包括向具有该肿瘤的个体给予有效治疗该肿瘤量的抗-CD38抗体-致弱干扰素α-2b融合结构。该结构可以包括本文描述或例示的任何结构。该个体优选是哺乳动物，更优选是非人灵长类动物，最优选是人类。该肿瘤可以包括B-细胞淋巴瘤、多发性骨髓瘤、非霍奇金淋巴瘤(non-Hodgkin’slymphoma)、慢性骨髓性白血病、慢性淋巴细胞白血病或急性骨髓性白血病。
可选择地融合到致弱干扰素α-2b蛋白质上的该抗CD38抗体可以用在检测从个体分离的组织标本中的CD38或CD38-阳性肿瘤细胞的方法中。通常情况下，该方法包括将特异地结合CD38的抗体与从个体分离的组织标本接触，和检测该组织标本中的该抗体和CD38或CD38阳性细胞的复合体。该组织标本可以已知具有CD38阳性肿瘤细胞或怀疑具有CD38阳性肿瘤细胞。该组织可以包括血液或骨髓。该CD38阳性肿瘤细胞可以是CD38-阳性B-细胞淋巴瘤细胞、多发性骨髓瘤细胞、非-Hodgkin淋巴瘤细胞、慢性骨髓性白血病细胞、慢性淋巴细胞白血病细胞或急性骨髓性白血病细胞。个体优选是哺乳动物，更优选是非人灵长类动物，最优选是人类。该方法可以包括从该个体分离该组织标本的步骤。该方法可以进一步包括将该抗体与不包括任何CD38阳性细胞的组织标本接触，例如，用作阴性对照。
附图说明
图1显示了抗CD38-致弱干扰素融合结构的实施例。
图2A和2B显示了X02.1的重链可变区的序列，相关结构和同源性最高的胚系抗体序列。由Kabat编号体系定义的CDR加有下划线。
图3A和3B显示了X02.1的轻链可变区的序列、相关结构和同源性最高的胚系抗体序列。由Kabat编号体系定义的CDR加有下划线。
图4A-4D显示了A02.1的轻链可变区的序列和相关结构。由Kabat编号体系定义的CDR加有下划线。
图5显示了A02.1的共有可变重链序列和相关结构。加框区包含如由Kabat编号体系和高级Chothia编号体系定义的CDR(如所示)。由Kabat编号体系定义的CDR以黑体显示。由高级Chothia编号体系定义的CDR加有下划线。
图6显示了A02.1的共有可变轻链序列和相关结构。加框区包含如由Kabat编号体系和高级Chothia编号体系定义的CDR(如所示)。由Kabat编号体系定义的CDR以黑体显示。由高级Chothia编号体系定义的CDR加有下划线。
图7A-7C显示了人源化重链可变区的重链可变区的序列。由Kabat编号体系定义的CDR加有下划线。
图8A-8C显示了人源化轻链可变区的重链可变区的序列。由Kabat编号体系定义的CDR加有下划线。
图9A和9B显示了A10.0的可变重链和相关结构。由Kabat编号体系定义的CDR加有下划线。
图10A和10B显示了A10.0的可变轻链和相关结构。由Kabat编号体系定义的CDR加有下划线。
图11显示了A10.0的可变重链共有序列和相关结构。加框区包含如由Kabat编号体系和高级Chothia编号体系定义的CDR(如所示)。由Kabat编号体系定义的CDR以黑体显示。由高级Chothia编号体系定义的CDR加有下划线。
图12显示了A10.0的可变轻链共有序列和相关结构。加框区包含如由Kabat编号体系和高级Chothia编号体系定义的CDR(如所示)。由Kabat编号体系定义的CDR以黑体显示。由高级Chothia编号体系定义的CDR加有下划线。
图13显示了如由流式细胞仪测量的A02.1变体与CD38-表达多发性骨髓瘤细胞系ARP-1的结合活性。实验细节表述在说明书的实施例中。
图14显示了如由流式细胞仪测量的A02.1变体与CD38表达多发性骨髓瘤细胞系NCI-H929的结合活性。实验细节描述在说明书实施例中。
图15和16显示了A02.1变体对多发性骨髓瘤细胞系ARP-1的抗增殖活性。A-同型(A-isotype)是不相关的与致弱干扰素融合的特异性抗体，其作为对照。实验细节描述在实施例中(细胞增殖试验)。
图17显示了IFN-α2b(内含子A)，与A02.1和A10.0和它们相应的未融合抗体X02.1和X10.0相比，对多发性骨髓瘤细胞系ARP-1的抗增殖活性。A-同型是不相关的与致弱干扰素融合的特异性抗体，其作为对照。实验细节描述在说明书实施例中(细胞增殖试验)。
图18显示了与未处理的对照相比，膜联蛋白V产物在当使用A02.1和A10.0和它们相应的未融合抗体X02.1和X10.0处理24小时后的CD38表达多发性骨髓瘤细胞系NCI-H929中的相对倍数变化。A-同型是不相关的与致弱干扰素融合的特异性抗体，其作为对照。实验细节描述在实施例中(膜联蛋白V试验)。
图19显示了与未处理细胞相比，半胱天冬酶激活在IFN-α2b(内含子A)，对比A02.1和有关结构，的CD38表达多发性骨髓瘤细胞系H929中的相对倍数变化。同型145D是不相关的与致弱干扰素融合的特异性抗体，其作为对照。实验细节描述在实施例中(半胱天冬酶试验)。
图20显示了IFN-α2b(内含子A)，对比A02.6和融合到野生型IFN-α2b(A02.6(野生型IFN))上的A02.6，对CD38-阴性细胞的脱靶活性。实验细节描述在实施例中(HEK-BLUETM)。
图21显示了在CD38-表达多发性骨髓瘤细胞系H929中，在抗CD38致弱IFN-α融合蛋白结构的IgG1和lgG4子类型之间的膜联蛋白V产物的相对倍数变化。A-同型是与致弱干扰素融合的非特异lgG4抗体，其作为对照。该抗体、A02.12和A10.0包含融合到致弱IFN-α上的lgG4恒定区，而A02.112和A10.59包含融合到致弱IFN-α上的lgG1恒定区。实验细节描述在实施例中(膜联蛋白V/7AAD试验)。
图22显示了由流式细胞仪测量的A10.0变体与CD38-表达多发性骨髓瘤细胞系NCI-H929的结合活性。实验细节表述在说明书实施例中。
图23显示了与未处理细胞相比，A10.0和A10.38的CD38表达多发性骨髓瘤细胞系H929中的半胱天冬酶激活。A-同型是不相关的融合到致弱IFN上的特异性抗体，其作为对照。实验细节描述在实施例中(半胱天冬酶试验)。
图24显示了与未处理细胞相比，半胱天冬酶激活在通过A10.0变体处理的CD38表达多发性骨髓瘤细胞系H929中的相对倍数变化。实验细节描述在实施例中(半胱天冬酶试验)。
图25显示了膜联蛋白V产物在通过A10.0变体处理的CD38表达多发性骨髓瘤细胞系H929中的相对倍数变化。实验细节描述在实施例中(膜联蛋白V/7AAD试验)。
图26显示了与A02.6、A10.0,A10.38和亲代A10A2.0嵌合抗体结构相比，IFN-α2b(内含子A)对Burkitt淋瘤细胞系Daudi的抗增殖活性。A-同型是不相关的与致弱INF融合的特异性抗体，其作为对照。实验细节描述在实施例中(细胞增殖试验)。
图27显示了人源化A10.0对比亲代A10A2.0嵌合抗体致弱干扰素结构对SCID小鼠中的皮下H929骨髓瘤肿瘤生长的影响。标记有“治疗期间”的横杠显示用化合物治疗的持续时间。
图28显示了融合到相同致弱IFN-α2b蛋白质上的A10.0变体的非-抗体抗原靶向IFN的活性。实验细节描述在实施例中(“脱靶实验”-iLite基因报告试验)。
图29显示了与A10.0变体和融合到野生型IFN-α2b的亲代A10A2.0嵌合抗体(A10A2.0嵌合体(野生型lFN))相比，IFN-α2b(内含子A)的“脱靶”活性。实验细节描述在实施例中(“脱靶实验”-HEK-BLUETM)。
图30显示了X910/12-HC-L0-干扰素-α(A145D)lgG4的可变重链共有序列和相关序列。加框区包含如由Kabat编号体系和高级Chothia编号体系定义的CDR(如所示)。由Kabat编号体系定义的CDR以黑体显示。由高级Chothia编号体系定义的CDR加有下划线。
具体实施方式
整个说明书和权利要求书使用了与公开有关的多种术语。赋予这样的术语本领域通常意义，除非另有说明。其他具体定义的术语被解释为与本文提供的定义一致。
术语个体和病人可互换地使用，并且包含任一动物。优选哺乳类动物，包括宠物和家畜哺乳类动物以及啮齿动物，包括小鼠(mice)、兔子和大鼠(rat)以及其它啮齿动物。更优选非人灵长类动物，例如食蟹猴，高度优选人类。
分子，例如抗体，已经被分离，如果它已经被改变和/或经由人之手已经从它的自然环境被移除。
本文使用的单数形式“一(a)”，“一(an)”和“该(the)”包括多个指示物，除非另有清楚地声明。
抗-CD38抗体-致弱干扰素α-2b融合结构包括，但是不局限于，本文描述和例示的任何抗体，该抗体特异地结合CD38，融合到致弱干扰素α-2b蛋白质上，包括SEQ ID NO:647、SEQ ID NO:648、SEQ ID NO:649、SEQ ID NO:650或SEQ ID NO:651的干扰素α-2b。在一些方面，将未突变干扰素α-2b蛋白质，比如SEQ ID NO:7，融合到抗-CD38抗体上使干扰素分子的生物活性变弱。在本公开中，致弱干扰素、致弱干扰素α-2b、IFN-α2b A145D和IFN-α2bA145G可以互换使用。
特异性不一定是绝对指定，但是可构成表示与抗原-阴性细胞相比，抗体IFN-α融合蛋白结构对抗原-阳性细胞的选择程度的相对概念。抗体IFN-α融合蛋白结构对抗原阳性细胞的特异性被抗体的可变区介导，通常被抗体的互补决定区(CDR)介导。与抗原-阴性细胞相比，结构对抗原阳性细胞可以具有100倍的特异性。
人CD38包括氨基酸序列SEQ ID NO:1，食蟹猴CD38包括氨基酸序列SEQ ID NO:2。
进一步观察到干扰素-α2b的生物活性能被减弱，这通过结合到细胞表面的干扰素受体的干扰素，被确定性氨基酸改变到蛋白质序列中的引入所介导。致弱干扰素分子能与特异地结合CD38的抗体融合，使得该抗体充当递送致弱干扰素到CD38-阳性细胞的载剂，具有致弱干扰素分子引起的脱靶干扰素活性的最终减小。进一步观察到将致弱干扰素融合到CD38抗体上没有显著地影响该抗体特异地结合表达CD38的细胞上的CD38的能力，包括动物体内的细胞。进一步观察到CD38抗体的变体能被设计和表达，使得在没有该抗体对CD38抗原的特异性或亲和性的明显损失情况下，该抗体具有降低的免疫原性和增加的稳定性和半衰期。这些变体抗体能融合到致弱干扰素上。
因此，特载了特异地结合CD38的抗体。还观察到这样的抗-CD38抗体可以用作致弱配体比如干扰素α的递送载剂。不受任何具体理论或作用机理的限制，认为该抗体指导干扰素α到它们结合的CD38-阳性细胞上，其中该干扰素可以与它的受体相互作用。认为该抗体作为递送载剂补偿该干扰素分子结合它的受体的减少的能力。从这层意义上说，该致弱干扰素具有降低的与健康细胞，尤其不表达CD38的细胞，上的它的受体相互作用的能力。认为通过将该致弱干扰素引入接近CD38-阳性细胞上的它的受体，该抗体可以增加该致弱干扰素结合它的有关受体的能力，并且产生治疗效果，同时展示出减小的引起对不表达CD38的健康细胞不想要的效果的能力。
该抗体可以是多克隆的，但是在一些方面，不是多克隆的。该抗体优选单克隆的。该抗体优选全长抗体。全长抗体通常包括可变区重链和可变区轻链。该抗体可包括抗体的衍生物或碎片或片段，该抗体的衍生物或碎片或片段保持抗原-结合特异性并且还优选保持亲代抗体分子(例如，对CD38)的大部分或全部亲和性。例如，衍生物可包括至少一个可变区(重链或轻链可变区)。合适的抗体衍生物和碎片的其他实施例包括，但不局限于，具有多表位特异性(polyepitopic specificity)的抗体、双特异抗体、多特异抗体、双体、单链分子以及FAb、F(Ab')2、Fd、Fabc和Fv分子、单链(Sc)抗体、单链Fv抗体(scFv)、单个抗体轻链、单个抗体重链、抗体链和其他分子的融合体、重链单体或二聚物、轻链单体或二聚物、一个重链和一个轻链组成的二聚物、和其他多聚体。单链Fv抗体可以是多价的。全部抗体类型都可以用于生成抗体衍生物、碎片和片段。抗体衍生物、碎片和/或片段可以被重组产生和被任何细胞类型，原核的或真核的，所表达。
在一些具体实施方式中，分离的抗体可以指单克隆抗体，对该抗体来说，IFN-α或致弱IFN-α已经被融合到重链IgG恒定区的C-端。当该单克隆抗体对CD38具有结合特异性，并且IFN-α是致弱I FN-α2b时，该分离的抗体也指本文的抗-CD38致弱IFN-α融合蛋白或抗-CD38致弱IFN-α融合结构。
在全长抗体中，每个重链由重链可变区(本文缩写为HCVR或VH)和重链恒定区组成。该重链恒定区由三个域CH1、CH2和CH3组成。每个轻链由轻链可变区(本文缩写为LCVR或VL)和轻链恒定区组成。轻链恒定区由一个域、CL组成。VH和VL区可进一步细分为高变区，称作为互补决定区(CDR)，该互补决定区散布有更保守的区，称作为骨架区(FWR或FR)。每个VH和VL由三个CDR和四个FWR组成，其从氨基-端到羧基-端按以下列顺序排列：FWR1、CDR1、FWR2、CDR2、FWR3、CDR3、FWR4。通常，改变FWR序列比改变CDR序列可能更小地干扰抗体的抗原结合特征。免疫球蛋白分子可能是任何类型(例如IgG、IgE、IgM、IgD、IgA和IgY)，种类(例如IgGl、lgG2、lgG3、lgG4、IgA1和lgA2)或子种类。
抗体可以来源于任何物种。例如，抗体可以是老鼠(mouse)、大鼠、山羊、马、猪、牛、骆驼、鸡、兔子、驴、大羊驼、单峰骆驼、鲨鱼或人抗体，以及来源于任何其它动物物种的抗体。为了用于治疗人类，在向人类病人给药时非人来源的抗体可以在结构上改变以具有更少的抗原性，包括通过嵌合(chimerization)或人源化或超人源化。
在一些方面，该抗体是人源化抗体。人源化抗体是那些其中氨基酸直接参与抗原结合的抗体，例如，互补决定区(CDR)，在有些情况下重链和/或轻链的骨架区(FWR)或它们的片段不是人起源，而该抗体中其余氨基酸是人或其他方面的人起源，例如人抗体骨架。人源化抗体还包括其中一个或更多个人蛋白质的残基被一个或更多个氨基酸取代修饰和/或一个或更多个人蛋白质的FWR残基由相应的非人残基替代的抗体。人源化的抗体也可以包括在人抗体或非人抗体中发现的残基。人源化抗体可以是超人源化抗体，例如，美国专利号7,732,578中所描述的。该抗体可以是人源化嵌合抗体。
在高度优选的方面，该抗体是全人的。全人抗体是那些其中整个分子是人或其它方面的人起源的抗体，或包括与抗体的人形式相同的氨基序列。全人抗体包括那些从人V基因库得到的抗体，例如，其中编码抗体可变区的人基因被重组表达。全人抗体可在其他生物体(例如，小鼠和转基因鼠(xenomouse)技术)或来自用编码人抗体的基因转化的其它生物体的细胞中表达。虽然如此，全人抗体可以包括不被人序列编码的氨基酸残基，例如，由随机或定点突变引入的突变。
该抗体可以是任何种类的全长抗体，例如，IgG1、lgG2或lgG4。这样的抗体的恒定域优选是人的。这样的抗体的可变区可以是非人起源，或优选地在起源上是人的或是人源化的。抗体碎片也可以用于代替全长抗体。
该抗体可以是微体(minibodies)。微体包括整个抗体的小版本，其在单链中编码整个抗体的必需元件。例如该微体可以由与铰链区融合的自然抗体的VH和VL域和免疫球蛋白分子的CH3域组成。
在一些方面，该抗体可以包括非免疫球蛋白来源的蛋白骨架。例如，可以参考文献(Ku&Schutz,Proc.Natl.Acad.Sci.USA 92:6552-6556,1995)，其描述了具有两个随机的环以形成CDR的四-螺旋束蛋白细胞色素b562，其被选择用于抗原结合。
自然序列变异可以存在于重和轻链和编码它们的基因中，因此，本领域技术人员会预期在本文描述和例示的抗体的氨基酸序列，或编码它们的基因中找到某种水平的变异。这些变体优选地保留亲代抗体的独特的结合特性(例如，特异性和亲和性)。这样的预期部分地是由于遗传密码的简并性，以及已知的进化成功的保守氨基酸序列变异，该变异没有明显地改变编码的蛋白质的性质。因此，这样的变体和同源物被认为实际上彼此相同，并且都被包括在本公开的范围内。该抗体因此包括具有单个或多个保持亲代抗体的生物特性(例如结合特异性和结合亲和性)的氨基酸取代、缺失、增加或替代的变体。该变体优选地是保守的，但是可以是非保守的。
分配给CDR和FWR的氨基酸位置可以根据免疫相关蛋白的Kabat序列，国立卫生研究院，马里兰州·贝塞斯达(Kabat Sequences of Proteins of ImmunologicalInterest,National Institutes of Health,Bethesda,Md.,)1987和1991(本文也称为Kabat编号体系)被定义。另外，该分配给CDR和FWR的氨基酸位置可以根据高级Chothia编号方案(http://www.bioinfo.org.uk/mdex.html)被定义。抗体的重链恒定区可由EU编号体系(Edelman,GM et al.(1969).,Proc.Natl.Acad.USA,63,78-85)定义。
根据Kabat编号体系，VH FWR和CDR可以如下定位：残基1-30(FWR1)、31-35(CDR1)、36-49(FWR2)、50-65(CDR2)、66-94(FWR3)、95-102(CDR3)和103-113(FWR4)，以及VL FWR和CDR如下定位：残基1–23(FWR1)、24-34(CDR1)、35-49(FWR2)、50-56(CDR2)、57-88(FWR3)、89-97(CDR3)和98-107(FWR4)。在有些情况下，可变区可以增加长度，根据Kabat编号体系，有些氨基酸可以由尾随字母的数字标出。本说明书不局限于如由Kabat编号体系定义的FWR和CDR，但是包括全部编号体系，包括权威编号体系或属于Chothia et al.(1987)J.Mol.Biol.196:901-17；Chothiaet al.(1989)Nature 342:877-83；和/或Al-Lazikaniet al.(1997)J.Mol.Biol.273:927-48；Honnegher et al.(2001)J.Mol.Biol.,309:657-70的编号体系；或Giudicelli et al.,(1997)Nucleic Acids Res.25:206-11中探讨的IMGT体系。在一些方面，CDR根据Kabat编号体系被定义。
在一些特定方面，对本文描述的任何重链CDR2子域来说，根据Kabat编号体系，五个C端氨基酸可以不直接参与抗原结合，因此，应该理解在没有实际负面影响抗原结合的情况下，这五个C端氨基酸中的任何一个或更多个可以用另一个自然发生的氨基酸取代。在一些方面，对本文描述的任何轻链CDR1子域来说，根据Kabat编号体系，四个N端氨基酸可以不直接参与抗原结合，因此，应该理解在没有实际负面影响抗原结合的情况下，这四个氨基酸中的任何一个或更多个可以用另一个自然发生的氨基酸取代。例如，如Padlan et al.(1995)FASEB J.9:133-139所描述的，重链CDR2的五个C端氨基酸和/或轻链CDR1的四个N端氨基酸可以不参与抗原结合。在一些方面，重链CDR2和轻链CDR1都不直接参与抗原结合。
在一些方面，氨基酸的化学类似物可以用在本文描述和/或例示的抗体中。氨基酸的化学类似物的使用有利于，例如，稳定比如如果要求向个体给予的分子。本文考虑的氨基酸的类似物包括，但是不局限于，在肽、多肽或蛋白质合成期间侧链的修饰，非自然氨基酸和/或它们的衍射物的并入，和交联剂(corsslinkers)和其它施加蛋白质性质分子或它们的类似物的构象约束的方法的使用。
抗体可以包括翻译后修饰物(modifications)或部分(moieties)，其可以影响抗体活性或稳定性。这些修饰物或部分包括，但是不局限于，甲基化、乙酰化、糖基化、硫酸化、磷酸化、羧基化和酰胺化部分和本领域熟知的其它部分。部分包括任何化学基团或通常在免疫球蛋白分子上发现的基团的组合，该免疫球蛋白分子呈自然态或其它的通过重组表达系统，包括原核与真核表达系统，添加到抗体。
本公开考虑的侧链修饰的实施例包括氨基基团修饰，比如通过经过与醛反应的还原烷基化，然后通过用NaBH4还原；用甲基乙酰亚酸盐(methylacetimidate)酰胺化；用乙酸酐酰化；用氰酸盐甲氨酰化氨基基团；用2,4,6-三硝基苯磺酸(TNBS)三硝基苄基化氨基基团；用丁二酸酐和四氢邻苯二甲酸酐(tetrahydrophthalic anhydride)酰化氨基基团；和用吡哆醛-5-磷酸酯(pyridoxal-5-phosphate)吡哆化赖氨酸(pyridoxylation oflysine)，然后用NaBH4还原。
通过用试剂例如2,3-丁二酮、苯甲酰甲醛和乙二醛形成杂环缩合(heterocycliccondensation)产物可以修饰精氨酸残基的胍基基团。
通过经由形成O-酰基异脲(O-acylisourea)活化碳二亚胺(carbodiimide)，然后通过随后衍生，例如，相应的酰胺可以修饰羧基基团。
通过方法，例如，用碘乙酸或碘乙酰胺羧甲基化；对磺基丙氨酸(cysteic acid)过甲酸氧化；用其它硫醇化合物形成混合的二硫化物；与马来酰亚胺、马来酸酐(maleicanhydride)或其它取代马来酰亚胺的反应，使用4-对氯汞苯甲酸盐(4-chloromercuribenzoate)，4-对氯汞苯硫酸(4-chloromercuriphenylsulphonic acid)，氯化苯汞，2-氯基汞-4-硝基酚(2-chloromercuri-4-nitrophenol)和其它汞制剂形成汞衍生物，用氰酸盐在碱性pH下甲氨酰化可以修饰巯基基团。
通过，例如，用N-溴代琥珀酸亚胺(N-bromosuccinimide)氧化或用2-羟基-5-硝基溴苄或磺酸苯基卤化物(sulphenyl halides)烷基化吲哚环可以修饰色氨酸残基。另一方面，通过用四硝基甲烷硝化形成3-硝基酪氨酸衍生物可以改变酪氨酸残基。
通过用碘乙酸衍生物烷基化或用焦碳酸二乙酯(diethylpyrocarbonate)N-乙酯基化可以完成对组氨酸残基的咪唑环的修饰。
交联剂可以用于，例如，稳定该抗体和结构的3D构象，利用同-双官能团交联剂，比如具有(CH2)n间隔基团，其中n＝l至n＝6，的双官能团酰亚胺酯，戊二醛、N-羟基丁二酰亚胺酯，和通常包括氨基-反应部分的异-双官能团试剂，该氨基-反应部分比如N-羟基琥珀酰亚胺和另一个基团特异反应部分，比如马来酰亚胺或二硫部分(SH)或碳化二亚胺(COOH)。
该抗体可以是亲和性成熟的(affinity matured)，或可以包括降低免疫原性的氨基酸改变，例如，通过移除预计的MHC II类-结合模体。通过调整它们的功能特性，比如抗体-依赖细胞介导的细胞毒作用(ADCC)，补体-依赖的细胞毒作用(CDC)、血清半衰期、生物分布和结合Fc受体或任何这些特征的组合，可以进一步提高本文描述的该抗体的治疗功用。通过蛋白质工程、糖工程(glyco-engineering)或化学方法可实现这个调整。取决于要求的治疗应用，增加或减小任何这些活性都可能是有益的。
方法中使用的糖工程的实施例如Shinkawa T.et al.(2003)J.Biol.Chem.278:3466-73中所描述。
该抗体可包括调整它的血清半衰期和生物分布的修饰，包括调整抗体与新生儿Fc受体(FcRn)，在保护IgG免受分解代谢和维持高血清抗体浓度中起关键作用的受体，的相互作用的修饰。血清半衰期调整修饰可发生在IgG1或lgG4的Fc区，包括三元取代的M252Y/S254T/T256E(根据EU编号体系编号(Edelman,G.M.et al.(1969)Proc.Natl.Acad.USA 63,78-85))，(例如，SEQ ID NO:656、SEQ ID NO:657、SEQ ID NO:658、SEQ ID NO:694)，如美国专利号7,083,784所描述的。其他取代可发生在位置250和428处，参见例如，美国专利号7,217,797，以及在位置307、380和434处，参见例如，WO 00/42072。恒定域氨基酸取代的实施例描述在美国公开号2009/0142340、2009/0068175和2009/0092599中，该取代调整与Fc受体的结合和随后的由这些受体介导的功能，包括FcRn结合和血清半衰期。裸抗体(nakedantibodies)可以具有重链C端赖氨酸遗漏或去除以降低异质性。人lgG4中的S228P取代(EU编号)能稳定体内抗体Fab臂交换(Labrin et al.(2009)Nature Biotechnology 27:8；767-773)。
已经知道链接到抗体分子的聚糖影响抗体与Fc受体和聚糖受体的相互作用，由此影响抗体活性，包括血清半衰期。所以，调整想要的抗体活性的确定糖型(glycoforms)能给予治疗优势。产生工程化糖型的方法包括但是不局限于在美国专利号6,602,684、7,326,681和7,388,081和PCT公开号WO 08/006554中描述的那些方法。或者，该抗体序列可被修饰以去除相关的糖型附着位点。
该抗体可以被标记或结合任何化学或生物分子部分。标记的抗体可以用于治疗、诊断或基础研究应用。这样的标记/结合物可以是可检测的，比如荧光染料、放射性同位素标记、酶、荧光蛋白和生物素。该标记/结合物可以是化学治疗剂、毒素、同位素和用于治疗条件，例如杀死癌细胞，的其他试剂。化学治疗剂可以是适合用于抗体用于目的任何试剂。
该抗体可以被已知的保护/阻断基团衍生化以防止溶蛋白性裂解或提高活性或稳定性。
该抗体优选对CD38上的表位具有亲和力，其包括解离常数(Kd)小于约1×10-2M。在一些具体实施方式中，Kd小于约1×10-3M。在另一些具体实施方式中，Kd小于约1×10-4M。在一些具体实施方式中，Kd小于约1×10-5M。在还有其它的具体实施方式中，Kd小于约1×10- 6M。在其它的具体实施方式中，Kd小于约1×10-7M。在其它的具体实施方式中，Kd小于约1×10-8M。在其它的具体实施方式中，Kd小于约1×10-9M。在其它的具体实施方式中，Kd小于约1×10-10M。在还有其它的具体实施方式中，Kd小于约1×10-11M。在一些具体实施方式中，Kd小于约1×10-12M。在其它的具体实施方式中，Kd小于约1×10-13M。在其它的具体实施方式中，Kd小于约1×10-14M。在还有其它的具体实施方式中，Kd小于约1×10-15M。亲和力值指通过标准方法学得到的那些值，包括表面等离子体共振，例如BiacoreTM分析法或利用
Red96(Forte Bio)Dip-and-Read系统的分析。
该抗体可以包括单链Fv分子(scFv)、Fab、或全IgG。任何这样的抗体可以包括具有如下氨基酸序列的重链，该氨基酸序列同氨基酸序列SEQ ID NO:659或SEQ ID NO:665或SEQ ID NO:736具有至少约85％、至少约90％、至少约95％、至少约96％、至少约97％、至少约98％、至少约99％、或至少约100％序列一致性，但是包括氨基酸序列SEQ ID NO:659的重链或它的变体排除氨基酸序列SEQ ID NO:13。能理解包括它们的重链中氨基酸改变的抗体保持对CD38特异地结合的能力。保持的CD38特异结合活性(包括亲和性)优选大约相当于没有该重链中任何氨基酸改变的抗体的结合活性(包括亲和性)，虽然该结合活性(包括亲和性)可以小于或大于没有该重链中任何氨基酸改变的抗体。该抗体可以包括具有如下氨基酸序列的轻链，该氨基酸序列同氨基酸序列SEQ ID NO:664或SEQ ID NO:666具有至少约85％、至少约90％、至少约95％、至少约96％、至少约97％、至少约98％、至少约99％、或至少约100％序列一致性，但是包括氨基酸序列SEQ ID NO:664的轻链或它的变体排除氨基酸序列SEQ ID NO:14。能理解包括它们的轻链中氨基酸改变的抗体保持对CD38特异地结合的能力。保持的CD38特异结合活性(包括亲和性)优选大约相当于没有该轻链中任何氨基酸改变的抗体的结合活性(包括亲和性)，虽然该结合活性(包括亲和性)可以小于或大于没有该轻链中任何氨基酸改变的抗体。
在一些方面，该重链FWR1包括氨基酸序列SEQ ID NO:199、SEQ ID NO:206、SEQ IDNO:214、SEQ ID NO:215、SEQ ID NO:217、SEQ ID NO:219、SEQ ID NO:389、SEQ ID NO:396、SEQ ID NO:400、SEQ ID NO:404、SEQ ID NO:408、SEQ ID NO:412、SEQ ID NO:416、SEQ IDNO:420、SEQ ID NO:424、SEQ ID NO:428、SEQ ID NO:432、SEQ ID NO:466、SEQ ID NO:470、SEQ ID NO:472、SEQ ID NO:474、SEQ ID NO:476、SEQ ID NO:478、SEQ ID NO:480、SEQ IDNO:482、SEQ ID NO:486、SEQ ID NO:488、SEQ ID NO:513、SEQ ID NO:537、SEQ ID NO:542、SEQ ID NO:547、SEQ ID NO:552、SEQ ID NO:557、SEQ ID NO:562、SEQ ID NO:567、SEQ IDNO:572、SEQ ID NO:577或SEQ ID NO:748，在一些方面，该重链FWR1包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:199、SEQ ID NO:214、SEQ ID NO:215、SEQ IDNO:217、SEQ ID NO:219、SEQ ID NO:389、SEQ ID NO:396、SEQ ID NO:400、SEQ ID NO:404、SEQ ID NO:408、SEQ ID NO:412、SEQ ID NO:416、SEQ ID NO:420、SEQ ID NO:424、SEQ IDNO:428、SEQ ID NO:432、SEQ ID NO:466、SEQ ID NO:470、SEQ ID NO:472、SEQ ID NO:474、SEQ ID NO:476、SEQ ID NO:478、SEQ ID NO:480、SEQ ID NO:482、SEQ ID NO:486、SEQ IDNO:488、SEQ ID NO:513、SEQ ID NO:537、SEQ ID NO:542、SEQ ID NO:547、SEQ ID NO:552、SEQ ID NO:557、SEQ ID NO:562、SEQ ID NO:567、SEQ ID NO:572、SEQ ID NO:577或SEQ IDNO:748至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％、或至少约99％序列一致性。在一些方面，该重链FWR2包括氨基酸序列SEQ ID NO:201、SEQ ID NO:211、SEQ ID NO:229、SEQ ID NO:391、SEQ ID NO:397、SEQ ID NO:401、SEQ ID NO:405、SEQ ID NO:409、SEQ ID NO:413、SEQ ID NO:417、SEQID NO:421、SEQ ID NO:425、SEQ ID NO:429、SEQ ID NO:433、SEQ ID NO:515、SEQ ID NO:520、SEQ ID NO:521、SEQ ID NO:522、SEQ ID NO:523、SEQ ID NO:524、SEQ ID NO:525、SEQID NO:538、SEQ ID NO:543、SEQ ID NO:548、SEQ ID NO:553、SEQ ID NO:558、SEQ ID NO:563、SEQ ID NO:568、SEQ ID NO:573、SEQ ID NO:578、SEQ ID NO:749或SEQ ID NO:750，在一些方面，该重链FWR2包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:201、SEQ ID NO:211、SEQ ID NO:229、SEQ ID NO:391、SEQ ID NO:397、SEQ ID NO:401、SEQID NO:405、SEQ ID NO:409、SEQ ID NO:413、SEQ ID NO:417、SEQ ID NO:421、SEQ ID NO:425、SEQ ID NO:429、SEQ ID NO:433、SEQ ID NO:515、SEQ ID NO:520、SEQ ID NO:521、SEQID NO:522、SEQ ID NO:523、SEQ ID NO:524、SEQ ID NO:525、SEQ ID NO:538、SEQ ID NO:543、SEQ ID NO:548、SEQ ID NO:553、SEQ ID NO:558、SEQ ID NO:563、SEQ ID NO:568、SEQID NO:573、SEQ ID NO:578、SEQ ID NO:749或SEQ ID NO:750至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该重链FWR3包括氨基酸序列SEQ ID NO:203、SEQ IDNO:210、SEQ ID NO:212、SEQ ID NO:213、SEQ ID NO:216、SEQ ID NO:218、SEQ ID NO:221、SEQ ID NO:226、SEQ ID NO:227、SEQ ID NO:230、SEQ ID NO:393、SEQ ID NO:399、SEQ IDNO:403、SEQ ID NO:407、SEQ ID NO:411、SEQ ID NO:415、SEQ ID NO:419、SEQ ID NO:423、SEQ ID NO:427、SEQ ID NO:431、SEQ ID NO:435、SEQ ID NO:468、SEQ ID NO:517、SEQ IDNO:530、SEQ ID NO:531、SEQ ID NO:532、SEQ ID NO:533、SEQ ID NO:540、SEQ ID NO:545、SEQ ID NO:550、SEQ ID NO:555、SEQ ID NO:560、SEQ ID NO:565、SEQ ID NO:570、SEQ IDNO:575、SEQ ID NO:580、SEQ ID NO:751或SEQ ID NO:752。在一些方面，该重链FWR3包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:203、SEQ ID NO:210、SEQ IDNO:212、SEQ ID NO:213、SEQ ID NO:216、SEQ ID NO:218、SEQ ID NO:221、SEQ ID NO:226、SEQ ID NO:227、SEQ ID NO:230、SEQ ID NO:393、SEQ ID NO:399、SEQ ID NO:403、SEQ IDNO:407、SEQ ID NO:411、SEQ ID NO:415、SEQ ID NO:419、SEQ ID NO:423、SEQ ID NO:427、SEQ ID NO:431、SEQ ID NO:435、SEQ ID NO:468、SEQ ID NO:517、SEQ ID NO:530、SEQ IDNO:531、SEQ ID NO:532、SEQ ID NO:533、SEQ ID NO:540、SEQ ID NO:545、SEQ ID NO:550、SEQ ID NO:555、SEQ ID NO:560、SEQ ID NO:565、SEQ ID NO:570、SEQ ID NO:575、SEQ IDNO:580、SEQ ID NO:751或SEQ ID NO:752至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％、至少约99％序列一致性。在一些方面，该重链FWR4包括氨基酸序列SEQ ID NO:205、SEQ ID NO:395、SEQ IDNO:519、SEQ ID NO:541、SEQ ID NO:546、SEQ ID NO:551、SEQ ID NO:556、SEQ ID NO:561、SEQ ID NO:566、SEQ ID NO:571、SEQ ID NO:576、SEQ ID NO:581或SEQ ID NO:753，在一些方面，该重链FWR4包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:205、SEQ ID NO:395、SEQ ID NO:519、SEQ ID NO:541、SEQ ID NO:546、SEQ ID NO:551、SEQ IDNO:556、SEQ ID NO:561、SEQ ID NO:566、SEQ ID NO:571、SEQ ID NO:576、SEQ ID NO:581或SEQ ID NO:753至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。能理解包括重链骨架区(FWR1、FWR2、FWR3和/或FWR4)氨基酸改变的抗体保持对CD38特异地结合的能力。保持的CD38特异结合活性(包括亲和性)优选大约相当于没有任何重链骨架区任何氨基酸改变的抗体的结合活性(包括亲和性)，虽然该结合活性(包括亲和性)可以小于或大于没有任何重链骨架区任何氨基酸改变的抗体。
在一些方面，该重链CDR1包括氨基酸序列SEQ ID NO:200、SEQ ID NO:224、SEQ IDNO:390、SEQ ID NO:514、SEQ ID NO:526、SEQ ID NO:527、SEQ ID NO:528、SEQ ID NO:529或SEQ ID NO:697，在一些方面，该重链CDR1包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:200、SEQ ID NO:224、SEQ ID NO:390、SEQ ID NO:514、SEQ ID NO:526、SEQ ID NO:527、SEQ ID NO:528、SEQ ID NO:529或SEQ ID NO:697至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该重链CDR2包括氨基酸序列SEQ ID NO:202、SEQ ID NO:392、SEQ ID NO:398、SEQ ID NO:402、SEQ ID NO:406、SEQ ID NO:410、SEQ IDNO:414、SEQ ID NO:418、SEQ ID NO:422、SEQ ID NO:426、SEQ ID NO:430、SEQ ID NO:434、SEQ ID NO:467、SEQ ID NO:471、SEQ ID NO:473、SEQ ID NO:475、SEQ ID NO:477、SEQ IDNO:479、SEQ ID NO:481、SEQ ID NO:483、SEQ ID NO:485、SEQ ID NO:487、SEQ ID NO:489、SEQ ID NO:516、SEQ ID NO:539、SEQ ID NO:544、SEQ ID NO:549、SEQ ID NO:554、SEQ IDNO:559、SEQ ID NO:564、SEQ ID NO:569、SEQ ID NO:574、SEQ ID NO:579、SEQ ID NO:698或SEQ ID NO:737，在一些方面，该重链CDR2包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:202、SEQ ID NO:392、SEQ ID NO:398、SEQ ID NO:402、SEQ ID NO:406、SEQ ID NO:410、SEQ ID NO:414、SEQ ID NO:418、SEQ ID NO:422、SEQ ID NO:426、SEQID NO:430、SEQ ID NO:434、SEQ ID NO:467、SEQ ID NO:471、SEQ ID NO:473、SEQ ID NO:475、SEQ ID NO:477、SEQ ID NO:479、SEQ ID NO:481、SEQ ID NO:483、SEQ ID NO:485、SEQID NO:487、SEQ ID NO:489、SEQ ID NO:516、SEQ ID NO:539、SEQ ID NO:544、SEQ ID NO:549、SEQ ID NO:554、SEQ ID NO:559、SEQ ID NO:564、SEQ ID NO:569、SEQ ID NO:574、SEQID NO:579、SEQ ID NO:698或SEQ ID NO:737至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％、至少约99％序列一致性。在一些方面，该重链CDR3包括氨基酸序列SEQ ID NO:204、SEQ ID NO:220、SEQ IDNO:222、SEQ ID NO:223、SEQ ID NO:228、SEQ ID NO:231、SEQ ID NO:394、SEQ ID NO:469、SEQ ID NO:518、SEQ ID NO:534、SEQ ID NO:535、SEQ ID NO:536、SEQ ID NO:699或SEQ IDNO:738，在一些方面，该重链CDR3包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:204、SEQ ID NO:220、SEQ ID NO:222、SEQ ID NO:223、SEQ ID NO:228、SEQ IDNO:231、SEQ ID NO:394、SEQ ID NO:469、SEQ ID NO:518、SEQ ID NO:534、SEQ ID NO:535、SEQ ID NO:536、SEQ ID NO:699或SEQ ID NO:738至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。能理解包括重链互补决定区(CDR1、CDR2、CDR 3和/或CDR 4)氨基酸改变的抗体保持对CD38特异地结合的能力。保持的CD38特异结合活性(包括亲和性)优选大约相当于没有任何重链互补决定区任何氨基酸改变的抗体的结合活性(包括亲和性)，虽然该结合活性(包括亲和性)可以小于或大于没有任何重链互补决定区任何氨基酸改变的抗体。
在一些方面，该轻链FWR1包括氨基酸序列SEQ ID NO:232、SEQ ID NO:247、SEQ IDNO:259、SEQ ID NO:260、SEQ ID NO:261、SEQ ID NO:436、SEQ ID NO:443、SEQ ID NO:447、SEQ ID NO:451、SEQ ID NO:455、SEQ ID NO:459、SEQ ID NO:463、SEQ ID NO:490、SEQ IDNO:497、SEQ ID NO:501、SEQ ID NO:509、SEQ ID NO:582、SEQ ID NO:607、SEQ ID NO:614、SEQ ID NO:618、SEQ ID NO:622、SEQ ID NO:626、SEQ ID NO:630、SEQ ID NO:634或SEQ IDNO:638，并且在一些方面，该轻链FWR1包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:232、SEQ ID NO:247、SEQ ID NO:259、SEQ ID NO:260、SEQ ID NO:261、SEQID NO:436、SEQ ID NO:443、SEQ ID NO:447、SEQ ID NO:451、SEQ ID NO:455、SEQ ID NO:459、SEQ ID NO:463、SEQ ID NO:490、SEQ ID NO:497、SEQ ID NO:501、SEQ ID NO:509、SEQID NO:582、SEQ ID NO:607、SEQ ID NO:614、SEQ ID NO:618、SEQ ID NO:622、SEQ ID NO:626、SEQ ID NO:630、SEQ ID NO:634或SEQ ID NO:638至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该轻链FWR2包括氨基酸序列SEQ ID NO:234、SEQ ID NO:246、SEQ ID NO:248、SEQ ID NO:281、SEQ ID NO:283、SEQ ID NO:285、SEQ ID NO:287、SEQID NO:289、SEQ ID NO:291、SEQ ID NO:293、SEQ ID NO:295、SEQ ID NO:297、SEQ ID NO:438、SEQ ID NO:444、SEQ ID NO:448、SEQ ID NO:452、SEQ ID NO:456、SEQ ID NO:460、SEQID NO:464、SEQ ID NO:492、SEQ ID NO:498、SEQ ID NO:502、SEQ ID NO:506、SEQ ID NO:510、SEQ ID NO:584、SEQ ID NO:592、SEQ ID NO:593、SEQ ID NO:609、SEQ ID NO:615、SEQID NO:619、SEQ ID NO:623、SEQ ID NO:627、SEQ ID NO:631、SEQ ID NO:635或SEQ ID NO:639，并且在一些方面，该轻链FWR2包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:234、SEQ ID NO:246、SEQ ID NO:248、SEQ ID NO:281、SEQ ID NO:283、SEQ IDNO:285、SEQ ID NO:287、SEQ ID NO:289、SEQ ID NO:291、SEQ ID NO:293、SEQ ID NO:295、SEQ ID NO:297、SEQ ID NO:438、SEQ ID NO:444、SEQ ID NO:448、SEQ ID NO:452、SEQ IDNO:456、SEQ ID NO:460、SEQ ID NO:464、SEQ ID NO:492、SEQ ID NO:498、SEQ ID NO:502、SEQ ID NO:506、SEQ ID NO:510、SEQ ID NO:584、SEQ ID NO:592、SEQ ID NO:593、SEQ IDNO:609、SEQ ID NO:615、SEQ ID NO:619、SEQ ID NO:623、SEQ ID NO:627、SEQ ID NO:631、SEQ ID NO:635或SEQ ID NO:639至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该轻链FWR3包括氨基酸序列SEQ ID NO:236、SEQ ID NO:245、SEQ ID NO:265、SEQID NO:266、SEQ ID NO:267、SEQ ID NO:271、SEQ ID NO:272、SEQ ID NO:274、SEQ ID NO:276、SEQ ID NO:277、SEQ ID NO:278、SEQ ID NO:279、SEQ ID NO:280、SEQ ID NO:282、SEQID NO:284、SEQ ID NO:286、SEQ ID NO:288、SEQ ID NO:290、SEQ ID NO:292、SEQ ID NO:294、SEQ ID NO:296、SEQ ID NO:298、SEQ ID NO:300、SEQ ID NO:302、SEQ ID NO:304、SEQID NO:306、SEQ ID NO:308、SEQ ID NO:310、SEQ ID NO:312、SEQ ID NO:314、SEQ ID NO:316、SEQ ID NO:318、SEQ ID NO:320、SEQ ID NO:323、SEQ ID NO:327、SEQ ID NO:331、SEQID NO:335、SEQ ID NO:339、SEQ ID NO:343、SEQ ID NO:347、SEQ ID NO:351、SEQ ID NO:355、SEQ ID NO:359、SEQ ID NO:363、SEQ ID NO:367、SEQ ID NO:371、SEQ ID NO:375、SEQID NO:379、SEQ ID NO:383、SEQ ID NO:387、SEQ ID NO:440、SEQ ID NO:445、SEQ ID NO:449、SEQ ID NO:453、SEQ ID NO:457、SEQ ID NO:461、SEQ ID NO:465、SEQ ID NO:494、SEQID NO:499、SEQ ID NO:503、SEQ ID NO:507、SEQ ID NO:511、SEQ ID NO:586、SEQ ID NO:611、SEQ ID NO:616、SEQ ID NO:620、SEQ ID NO:624、SEQ ID NO:628、SEQ ID NO:632、SEQID NO:636或SEQ ID NO:640，并且在一些方面，该轻链FWR3包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:236、SEQ ID NO:245、SEQ ID NO:265、SEQ ID NO:266、SEQ ID NO:267、SEQ ID NO:271、SEQ ID NO:272、SEQ ID NO:274、SEQ ID NO:276、SEQ IDNO:277、SEQ ID NO:278、SEQ ID NO:279、SEQ ID NO:280、SEQ ID NO:282、SEQ ID NO:284、SEQ ID NO:286、SEQ ID NO:288、SEQ ID NO:290、SEQ ID NO:292、SEQ ID NO:294、SEQ IDNO:296、SEQ ID NO:298、SEQ ID NO:300、SEQ ID NO:302、SEQ ID NO:304、SEQ ID NO:306、SEQ ID NO:308、SEQ ID NO:310、SEQ ID NO:312、SEQ ID NO:314、SEQ ID NO:316、SEQ IDNO:318、SEQ ID NO:320、SEQ ID NO:323、SEQ ID NO:327、SEQ ID NO:331、SEQ ID NO:335、SEQ ID NO:339、SEQ ID NO:343、SEQ ID NO:347、SEQ ID NO:351、SEQ ID NO:355、SEQ IDNO:359、SEQ ID NO:363、SEQ ID NO:367、SEQ ID NO:371、SEQ ID NO:375、SEQ ID NO:379、SEQ ID NO:383、SEQ ID NO:387、SEQ ID NO:440、SEQ ID NO:445、SEQ ID NO:449、SEQ IDNO:453、SEQ ID NO:457、SEQ ID NO:461、SEQ ID NO:465、SEQ ID NO:494、SEQ ID NO:499、SEQ ID NO:503、SEQ ID NO:507、SEQ ID NO:511、SEQ ID NO:586、SEQ ID NO:611、SEQ IDNO:616、SEQ ID NO:620、SEQ ID NO:624、SEQ ID NO:628、SEQ ID NO:632、SEQ ID NO:636或SEQ ID NO:640至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该轻链FWR4包括氨基酸序列SEQ ID NO:238、SEQ ID NO:442、SEQ ID NO:446、SEQ ID NO:450、SEQID NO:454、SEQ ID NO:458、SEQ ID NO:462、SEQ ID NO:496、SEQ ID NO:500、SEQ ID NO:504、SEQ ID NO:508、SEQ ID NO:512、SEQ ID NO:588、SEQ ID NO:613、SEQ ID NO:617、SEQID NO:621、SEQ ID NO:625、SEQ ID NO:629、SEQ ID NO:633、SEQ ID NO:637或SEQ ID NO:641，并且在一些方面，该轻链FWR4包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:238、SEQ ID NO:442、SEQ ID NO:446、SEQ ID NO:450、SEQ ID NO:454、SEQ IDNO:458、SEQ ID NO:462、SEQ ID NO:496、SEQ ID NO:500、SEQ ID NO:504、SEQ ID NO:508、SEQ ID NO:512、SEQ ID NO:588、SEQ ID NO:613、SEQ ID NO:617、SEQ ID NO:621、SEQ IDNO:625、SEQ ID NO:629、SEQ ID NO:633、SEQ ID NO:637或SEQ ID NO:641至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。能理解包括轻链骨架区(FWR1、FWR2、FWR3、和/或FWR4)氨基酸改变的抗体保持对CD38特异地结合的能力。保持的CD38特异结合活性(包括亲和性)优选大约相当于没有任何轻链骨架区任何氨基酸改变的抗体的结合活性(包括亲和性)，虽然该结合活性(包括亲和性)可以小于或大于没有任何轻链骨架区任何氨基酸改变的抗体。
在一些方面，该轻链CDR1包括氨基酸序列SEQ ID NO:233、SEQ ID NO:250、SEQ IDNO:525、SEQ ID NO:255、SEQ ID NO:262、SEQ ID NO:263、SEQ ID NO:319、SEQ ID NO:322、SEQ ID NO:325、SEQ ID NO:329、SEQ ID NO:333、SEQ ID NO:337、SEQ ID NO:341、SEQ IDNO:345、SEQ ID NO:349、SEQ ID NO:353、SEQ ID NO:357、SEQ ID NO:361、SEQ ID NO:365、SEQ ID NO:369、SEQ ID NO:373、SEQ ID NO:377、SEQ ID NO:381、SEQ ID NO:385、SEQ IDNO:437、SEQ ID NO:491、SEQ ID NO:583、SEQ ID NO:589、SEQ ID NO:590、SEQ ID NO:608或SEQ ID NO:696，并且在一些方面，该轻链CDR1包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:233、SEQ ID NO:250、SEQ ID NO:525、SEQ ID NO:255、SEQ IDNO:262、SEQ ID NO:263、SEQ ID NO:319、SEQ ID NO:322、SEQ ID NO:325、SEQ ID NO:329、SEQ ID NO:333、SEQ ID NO:337、SEQ ID NO:341、SEQ ID NO:345、SEQ ID NO:349、SEQ IDNO:353、SEQ ID NO:357、SEQ ID NO:361、SEQ ID NO:365、SEQ ID NO:369、SEQ ID NO:373、SEQ ID NO:377、SEQ ID NO:381、SEQ ID NO:385、SEQ ID NO:437、SEQ ID NO:491、SEQ IDNO:583、SEQ ID NO:589、SEQ ID NO:590、SEQ ID NO:608或SEQ ID NO:696至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该轻链CDR2包括氨基酸序列SEQ ID NO:235、SEQ ID NO:249、SEQ ID NO:253、SEQ ID NO:264、SEQ ID NO:299、SEQ ID NO:301、SEQID NO:303、SEQ ID NO:305、SEQ ID NO:307、SEQ ID NO:309、SEQ ID NO:311、SEQ ID NO:313、SEQ ID NO:315、SEQ ID NO:317、SEQ ID NO:326、SEQ ID NO:330、SEQ ID NO:334、SEQID NO:338、SEQ ID NO:342、SEQ ID NO:346、SEQ ID NO:350、SEQ ID NO:354、SEQ ID NO:358、SEQ ID NO:362、SEQ ID NO:366、SEQ ID NO:370、SEQ ID NO:374、SEQ ID NO:378、SEQID NO:382、SEQ ID NO:386、SEQ ID NO:439、SEQ ID NO:493、SEQ ID NO:585、SEQ ID NO:591、SEQ ID NO:605、SEQ ID NO:610或SEQ ID NO:747，并且在一些方面，该轻链CDR2包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:235、SEQ ID NO:249、SEQ IDNO:253、SEQ ID NO:264、SEQ ID NO:299、SEQ ID NO:301、SEQ ID NO:303、SEQ ID NO:305、SEQ ID NO:307、SEQ ID NO:309、SEQ ID NO:311、SEQ ID NO:313、SEQ ID NO:315、SEQ IDNO:317、SEQ ID NO:326、SEQ ID NO:330、SEQ ID NO:334、SEQ ID NO:338、SEQ ID NO:342、SEQ ID NO:346、SEQ ID NO:350、SEQ ID NO:354、SEQ ID NO:358、SEQ ID NO:362、SEQ IDNO:366、SEQ ID NO:370、SEQ ID NO:374、SEQ ID NO:378、SEQ ID NO:382、SEQ ID NO:386、SEQ ID NO:439、SEQ ID NO:493、SEQ ID NO:585、SEQ ID NO:591、SEQ ID NO:605、SEQ IDNO:610或SEQ ID NO:747至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。在一些方面，该轻链CDR3包括氨基酸序列SEQ ID NO:237、SEQ ID NO:244、SEQ ID NO:251、SEQ ID NO:254、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQ ID NO:268、SEQ ID NO:269、SEQID NO:270、SEQ ID NO:273、SEQ ID NO:275、SEQ ID NO:321、SEQ ID NO:324、SEQ ID NO:328、SEQ ID NO:332、SEQ ID NO:336、SEQ ID NO:340、SEQ ID NO:344、SEQ ID NO:348、SEQID NO:352、SEQ ID NO:356、SEQ ID NO:360、SEQ ID NO:364、SEQ ID NO:368、SEQ ID NO:372、SEQ ID NO:376、SEQ ID NO:380、SEQ ID NO:384、SEQ ID NO:388、SEQ ID NO:441、SEQID NO:495、SEQ ID NO:587、SEQ ID NO:594、SEQ ID NO:595、SEQ ID NO:596、SEQ ID NO:597、SEQ ID NO:598、SEQ ID NO:599、SEQ ID NO:600、SEQ ID NO:601、SEQ ID NO:602、SEQID NO:603、SEQ ID NO:604、SEQ ID NO:606或SEQ ID NO:612，并且在一些方面，该轻链CDR3包括如下氨基酸序列，该氨基酸序列具有同氨基酸序列SEQ ID NO:237、SEQ ID NO:244、SEQ ID NO:251、SEQ ID NO:254、SEQ ID NO:256、SEQ ID NO:257、SEQ ID NO:258、SEQID NO:268、SEQ ID NO:269、SEQ ID NO:270、SEQ ID NO:273、SEQ ID NO:275、SEQ ID NO:321、SEQ ID NO:324、SEQ ID NO:328、SEQ ID NO:332、SEQ ID NO:336、SEQ ID NO:340、SEQID NO:344、SEQ ID NO:348、SEQ ID NO:352、SEQ ID NO:356、SEQ ID NO:360、SEQ ID NO:364、SEQ ID NO:368、SEQ ID NO:372、SEQ ID NO:376、SEQ ID NO:380、SEQ ID NO:384、SEQID NO:388、SEQ ID NO:441、SEQ ID NO:495、SEQ ID NO:587、SEQ ID NO:594、SEQ ID NO:595、SEQ ID NO:596、SEQ ID NO:597、SEQ ID NO:598、SEQ ID NO:599、SEQ ID NO:600、SEQID NO:601、SEQ ID NO:602、SEQ ID NO:603、SEQ ID NO:604、SEQ ID NO:606或SEQ ID NO:612至少约85％、至少约90％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％或至少约99％序列一致性。能理解包括轻链互补决定区(CDR1、CDR2和/或CDR 3)氨基酸改变的抗体保持对CD38特异地结合的能力。保持的CD38特异结合活性(包括亲和性)优选大约相当于没有任何链链互补决定区任何氨基酸改变的抗体的结合活性(包括亲和性)，虽然该结合活性(包括亲和性)可以小于或大于没有任何链链互补决定区任何氨基酸改变的抗体。
在一些方面，该抗体包括特定重和轻链对。具有氨基酸序列SEQ ID NO:659的重链可以与具有氨基酸序列SEQ ID NO:664的任何轻链成对，或者具有氨基酸序列SEQ ID NO:665的重链可以与具有氨基酸序列SEQ ID NO:666的任何轻链成对，或者具有氨基酸序列SEQ ID NO:736的重链可以与具有氨基酸序列SEQ ID NO:664的任何轻链成对。
可变重和可变轻链对可以包括下表中的对：
该抗体可以融合到致弱配体上，例如，以形成抗体-致弱配体结构，由于该致弱配体对细胞表面受体的作用，该结构关于激活信号通路显示出提高的抗原-特异性指数。这些结构是基于一定的观察，在抗体-配体结构背景中，可以以配体对抗原-阴性细胞的活性显著减弱，同时配体对抗原-阳性细胞的活性，如果存在的话，仅仅轻度地减弱的方式突变该配体部分。与抗原-阴性细胞相比，这样的结构对抗原-阳性细胞显示比游离配体大于一个、两个、三个、四个或五个数量级的效价(potency)。在一些方面，该抗体-致弱配体结构对抗原-阳性细胞保持至少1％、至少10％、至少20％、至少30％、至少40％或至少50％的效价，作为非致弱游离(即，不附着在抗体上)配体。在一些方面，该抗体-致弱配体结构保持非致弱游离(即，不附着在抗体上)配体的最大活性的至少30％、至少50％、至少75％、或至少90％。最大活性包括在剂量-响应曲线的高处，坪部分(plateau portion)的信号活性(或它的下游效应)的量，在此处进一步增加试剂不会进一步增加反应量。
在一些方面，该融合到干扰素配体中的致弱突变并且包括干扰素配体中的致弱突变的抗体比未融合抗体以大于10倍，优选大于50倍，优选大于100倍，优选大于1000倍或优选大于10000倍的量增加抗原-特异性指数(ASI)。ASI包括相对于游离未突变多肽配体，在靶抗原阳性细胞上的抗体-IFN配体结构的信号活性的成倍增加的效价被乘以相对于游离未突变多肽配体，在靶抗原阴性细胞上的信号活性的成倍减小的效价。效价可以由EC50值定量表示，该值是剂量-响应曲线的数学中点，其中剂量指实验中配体或抗体-配体结构的浓度，响应指在特定剂量下细胞对配体的信号活性的定量反应。因此，例如，当显示第一化合物具有EC50(例如，以摩尔单位表达)比第二化合物的EC50在相同细胞上低10倍，通常当用相同方法测量时，该第一化合物称为具有高10倍的效价。相反，当显示第一化合物具有EC50比第二化合物的EC50在相同细胞上高10倍，通常当用相同方法测量时，该第一化合物称为具有低10倍的效价。
该抗体优选能够结合到CD38阳性细胞上。该抗体可以以小于约100nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约75nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约50nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约30nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约25nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约20nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约18nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约15nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约13nM的EC50值结合到CD38阳性细胞上。该抗体可以以小于约10nM的EC50值结合到CD38阳性细胞上。
连接到该抗体的干扰素优选包括它的氨基酸序列改变，包括致使干扰素在刺激细胞上的它的各自受体中具有较小活性的点突变和/或缺失，该细胞缺乏细胞表面表达结合该抗体的CD38抗原。高优选的干扰素α变体包括氨基酸在SEQ ID NO:7的干扰素α2b分子的位置168处的改变。例如，位置168处的氨基酸，其在亲代IFN-α2b分子中是丙氨酸，优选变成甘氨酸(Gly/G)(SEQ ID NO:650)或天冬氨酸(Asp/D)(SEQ ID NO:647)。在一些方面，当IFN-α2b被融合到IgG重链恒定域例如人IgG1或人IgG4重链恒定域时，IFN-α2b在它的N端被截断。该截断的IFN-α2b不具有SEQ ID NO:7的23个N端氨基酸(Met 1到Gly 23被删除)，并且该截断的IFN-α2b包括氨基酸序列SEQ ID NO:648。该截断的IFN-α2b还包括氨基酸改变，原来是位置168，但是在该切断的蛋白质中变成了位置145(例如，丙氨酸168变成了丙氨酸145)。在该截断的IFN-α2b中，丙氨酸优选改变成甘氨酸(Gly/G)(SEQ ID NO:651)或天冬氨酸(Asp/D)(SEQ ID NO:649)。具有A145D改变的干扰素(SEQ ID NO:647或SEQ ID NO:649)尤其优选作为融合到本公开的抗体上的致弱配体。任何这些点-突变(point-mutated)，IFN-α的致弱形式可被连接到本文描述的任何抗体上，例如，作为抗体-致弱干扰素结构。
该抗体和该干扰素之间的连接优选包括融合，例如，干扰素的N或C端和抗体的重或轻链的N或C端之间的肽键。在高优选方面，该抗体和该干扰素直接没有连接子存在，该抗体和该干扰素因此直接融合。认为没有中介连接肽的直接融合提供了至少可测量程度的致弱干扰素蛋白，还认为这个致弱被加以起源于引入到该干扰素蛋白中的突变的该干扰素蛋白的致弱，包括本文描述和例示的那些。
本公开特载了编码抗体和它们的子域(例如，FWR和CDR)多核苷酸序列。多核苷酸包括，但是不局限于RNA、DNA、cDNA、RNA和DNA的杂交、和单、双或三链的RNA、DNA或它们的杂交的链。
在一些方面，该多核苷酸编码特异地结合CD38上的表位的抗体的重链。该多核苷酸可以编码包含以下任何氨基酸序列的重链：SEQ ID NO:667、SEQ ID NO:668、SEQ ID NO:679、SEQ ID NO:680、SEQ ID NO:681、SEQ ID NO:682、SEQ ID NO:683、SEQ ID NO:684、SEQID NO:、SEQ ID NO:685、SEQ ID NO:686、SEQ ID NO:695、SEQ ID NO:724、SEQ ID NO:725、SEQ ID NO:726、SEQ ID NO:727、SEQ ID NO:732、SEQ ID NO:733、SEQ ID NO:734、SEQ IDNO:735、SEQ ID NO:743、SEQ ID NO:744、SEQ ID NO:745或SEQ ID NO:746。该多核苷酸可以编码包含以下任何氨基酸序列的轻链：SEQ ID NO:669、SEQ ID NO:670、SEQ ID NO:671、SEQ ID NO:672、SEQ ID NO:673、SEQ ID NO:674、SEQ ID NO:675、SEQ ID NO:676、SEQ IDNO:677、SEQ ID NO:678、SEQ ID NO:688、SEQ ID NO:689、SEQ ID NO:690、SEQ ID NO:691、SEQ ID NO:692、SEQ ID NO:693、SEQ ID NO:702、SEQ ID NO:703、SEQ ID NO:712、SEQ IDNO:713、SEQ ID NO:714、SEQ ID NO:715、SEQ ID NO:716、SEQ ID NO:717、SEQ ID NO:718或SEQ ID NO:719。该多核苷酸可以包括以下任何核酸序列：SEQ ID NO:667、SEQ ID NO:668、SEQ ID NO:679、SEQ ID NO:680、SEQ ID NO:681、SEQ ID NO:682、SEQ ID NO:683、SEQID NO:684、SEQ ID NO:、SEQ ID NO:685、SEQ ID NO:686、SEQ ID NO:695、SEQ ID NO:724、SEQ ID NO:725、SEQ ID NO:726、SEQ ID NO:727、SEQ ID NO:732、SEQ ID NO:733、SEQ IDNO:734、SEQ ID NO:735、SEQ ID NO:743、SEQ ID NO:744、SEQ ID NO:745、SEQ ID NO:746、SEQ ID NO:669、SEQ ID NO:670、SEQ ID NO:671、SEQ ID NO:672、SEQ ID NO:673、SEQ IDNO:674、SEQ ID NO:675、SEQ ID NO:676、SEQ ID NO:677、SEQ ID NO:678、SEQ ID NO:688、SEQ ID NO:689、SEQ ID NO:690、SEQ ID NO:691、SEQ ID NO:692、SEQ ID NO:693、SEQ IDNO:702、SEQ ID NO:703、SEQ ID NO:712、SEQ ID NO:713、SEQ ID NO:714、SEQ ID NO:715、SEQ ID NO:716、SEQ ID NO:717、SEQ ID NO:718或SEQ ID NO:719。该多核苷酸可以包括核酸序列，该核酸序列具有同任何SEQ ID NO:667、SEQ ID NO:668、SEQ ID NO:679、SEQ IDNO:680、SEQ ID NO:681、SEQ ID NO:682、SEQ ID NO:683、SEQ ID NO:684、SEQ ID NO:、SEQID NO:685、SEQ ID NO:686、SEQ ID NO:695、SEQ ID NO:724、SEQ ID NO:725、SEQ ID NO:726、SEQ ID NO:727、SEQ ID NO:732、SEQ ID NO:733、SEQ ID NO:734、SEQ ID NO:735、SEQID NO:743、SEQ ID NO:744、SEQ ID NO:745、SEQ ID NO:746、SEQ ID NO:669、SEQ ID NO:670、SEQ ID NO:671、SEQ ID NO:672、SEQ ID NO:673、SEQ ID NO:674、SEQ ID NO:675、SEQID NO:676、SEQ ID NO:677、SEQ ID NO:678、SEQ ID NO:688、SEQ ID NO:689、SEQ ID NO:690、SEQ ID NO:691、SEQ ID NO:692、SEQ ID NO:693、SEQ ID NO:702、SEQ ID NO:703、SEQID NO:712、SEQ ID NO:713、SEQ ID NO:714、SEQ ID NO:715、SEQ ID NO:716、SEQ ID NO:717、SEQ ID NO:718或SEQ ID NO:719至少约80％、至少约85％、至少约86％、至少约87％、至少约88％、至少约89％、至少约90％、至少约91％、至少约92％、至少约93％、至少约94％、至少约95％、至少约96％、至少约97％、至少约98％,或至少约99％序列一致性，并且在一些方面，这样的变体优选编码由以下多核苷酸序列编码的相同氨基酸：SEQ ID NO:667、SEQID NO:668、SEQ ID NO:679、SEQ ID NO:680、SEQ ID NO:681、SEQ ID NO:682、SEQ ID NO:683、SEQ ID NO:684、SEQ ID NO:、SEQ ID NO:685、SEQ ID NO:686、SEQ ID NO:695、SEQ IDNO:724、SEQ ID NO:725、SEQ ID NO:726、SEQ ID NO:727、SEQ ID NO:732、SEQ ID NO:733、SEQ ID NO:734、SEQ ID NO:735、SEQ ID NO:743、SEQ ID NO:744、SEQ ID NO:745、SEQ IDNO:746、SEQ ID NO:669、SEQ ID NO:670、SEQ ID NO:671、SEQ ID NO:672、SEQ ID NO:673、SEQ ID NO:674、SEQ ID NO:675、SEQ ID NO:676、SEQ ID NO:677、SEQ ID NO:678、SEQ IDNO:688、SEQ ID NO:689、SEQ ID NO:690、SEQ ID NO:691、SEQ ID NO:692、SEQ ID NO:693、SEQ ID NO:702、SEQ ID NO:703、SEQ ID NO:712、SEQ ID NO:713、SEQ ID NO:714、SEQ IDNO:715、SEQ ID NO:716、SEQ ID NO:717、SEQ ID NO:718或SEQ ID NO:719。优选地，由该多核苷酸变体编码的抗体将特异地结合CD38，具有亲和性约等于由亲代(非变体)多核苷酸序列编码的抗体的亲和性。可以测量亲和性，例如，根据本文描述和例示的任何技术，包括实施例中描述的技术。多核苷酸序列和变体多核苷酸序列的补体也在本公开的范围内。
还包含在本公开之内的是包括本公开的该多核苷酸的载体。该载体可以是表达载体。因此，提供了含有编码有关多肽的序列的重组表达载体。该表达载体可以包含一个或多个附加序列(additional sequences)，例如，但是不局限于，调控序列、筛选标记、纯化标签或多聚腺苷酸化信号。这样的调控元件可以包括转录启动子、增强子、mRNA核糖体结合位点或控制转录和翻译的终止序列。
表达载体，特别是哺乳动物表达载体可以包含一个或多个非转录的元件，例如复制起点、连接到待表达基因上的合适的启动子和增强子、其它5'或3'侧翼非转录的序列、5'或3'非翻译的序列(例如，必要核糖体结合位点)、聚腺苷酸化位点、剪切供体和受体位点、或转录终止序列。赋予特定宿主中的复制能力的复制起点也可以被包括在内。
载体可以用于转化任何对本领域技术人员熟知的一系列广泛宿主细胞，优选能够表达抗体的宿主细胞。载体包括，但不局限于，质粒、噬菌粒、粘粒、杆状病毒类、杆粒(bacmids)、细菌人工染色体(BAC)、酵母人工染色体(YAC)和杆状病毒，以及其它细菌、真核、酵母和病毒载体。合适的宿主细胞包括，但是不局限于CHO细胞、HEK293细胞或任何已知和或制备的真核稳定细胞系，并且还包括细菌、酵母和昆虫细胞。
该抗体还可以通过杂交瘤细胞制备；制备杂交瘤的方法在本领域中已经非常熟知和接受。
根据本公开，还观察到当具有一个或多个实际上降低配体对干扰素受体亲和性的突变的干扰素α配体连接到靶向突变的干扰素α配体用以靶向显示抗体的相应抗原的细胞的抗-CD38抗体上时，靶抗原-阳性细胞上的配体的活性被维持，而非-靶抗原-阴性细胞上的配体活性实际上被降低。净结果是与抗原-阴性非-靶细胞相比，配体信号分子在激活它的抗原-阳性靶细胞上的受体中具有更大的效价，这提供了一种降低由脱靶配体活性引起的毒性的手段。
在一些方面，多肽结构包括连接到抗-CD38抗体或它的抗原结合部分上的IFN-α变体。这样的多肽在体内能够对CD38-阳性肿瘤细胞高效价发挥IFN的抗-增殖活性，而对CD38-阴性、非肿瘤细胞发挥较低效价。
本公开还提供了包括本公开的抗体和抗体-致弱干扰素结构的组合物。这些组合物能进一步包括至少一种任何合适的助剂，例如，但是不局限于，一种或更多种稀释剂、粘合剂、稳定剂、缓冲剂、盐分、亲脂性溶剂、防腐剂、佐剂、或其它合适的载体和/或赋形剂。药学上可接受的助剂是优选的。该组合物可以包括本文描述和/或例示的任何抗体和抗体-致弱干扰素结构和可接受的载体，例如药学上可接受的载体。合适的载体包括不干扰抗体和/或干扰素的生物活性的任何介质，并且优选对它被给予的宿主没有毒。该载体可以是水溶液，例如，水、盐水、或乙醇、或生理学上可相容的缓冲液，例如Hanks溶液、Ringer溶液、或生理盐水缓冲液。该载体可以包含配方剂(formulatory agents)，例如，悬浮、稳定和/或分散剂。
组合物中有用的药用赋形剂和添加剂包括但是不局限于蛋白质、肽、氨基酸、脂类和碳水化合物(例如，糖、包括单糖、二、三、四-、和寡糖；衍生糖，例如，糖醇、醛糖酸、酯化糖和其它已知糖；和多糖或糖聚合物)，其可单独或以组合形式出现，包括单独或组合的任何合适的重量或体积。典型的蛋白质赋形剂包括血清白蛋白，例如人血清白蛋白(HSA)、重组人白蛋白(rHA)、明胶(gelatin)、酪蛋白、和其它已知蛋白质。也可起缓冲能力作用的代表性的氨基酸包括丙氨酸、甘氨酸、精氨酸、甜菜碱、组氨酸、谷氨酸、天冬氨酸、半胱氨酸、赖氨酸、亮氨酸、异亮氨酸、缬氨酸、蛋氨酸、苯丙氨酸和天冬甜素。一个优选的氨基酸是组氨酸。第二优选的氨基酸是精氨酸。
合适用在组合物中的碳水化合物赋形剂包括，例如，单糖，比如果糖、麦芽糖、半乳糖、葡糖糖、D-甘露糖和山梨糖；二糖，比如乳糖、蔗糖、海藻糖和纤维二糖；多糖，比如蜜三糖、松三糖、麦芽糊精、葡萄聚糖和淀粉；和糖醇，比如甘露糖、木糖醇、麦芽糖醇、乳糖醇、木糖醇(葡萄糖醇)和肌醇。用在本公开中的优选的碳水化合物赋形剂是甘露醇、海藻糖和蜜三糖。
抗体组合物还可包括缓冲剂或pH调节剂；典型地，该缓冲剂是从有机酸或碱制备的盐。代表性的缓冲剂包括有机酸盐，比如柠檬酸盐、抗坏血酸盐、葡萄糖酸盐、碳酸盐、酒石酸盐、琥珀酸盐、醋酸盐、或邻苯二甲酸盐；三甲醇氨基甲烷(Tris)、基丁三醇盐酸盐(tromethamine hydrochloride)或磷酸盐缓冲剂。用在本组合物中优选的缓冲剂是有机酸盐，比如柠檬酸盐。
此外，本公开的组合物可包括聚合赋形剂/添加剂，比如聚乙烯吡咯烷酮、聚蔗糖(ficolls)(聚合糖)、葡萄糖结合剂(dextrates)(例如，环糊精，比如2-羟丙基-β-环糊精)、聚乙烯乙二醇、抗菌剂、抗氧化剂、抗静电剂、表面活性剂(例如，聚山梨醇酯，比如“
20”和“
80”)、脂类(例如，磷脂、脂肪酸)；类固醇(例如，胆固醇)和螯合剂(例如，EDTA)。
该组合物还可以被配制成缓释载剂(sustained release vehicles)或药性持久的制剂(depot preparations)。例如，该组合物可以与合适的聚合或疏水材料(例如，作为可接受的油中的乳剂)或离子交换树脂一起配制，或作为微溶的衍生物，例如，作为微溶的盐。脂质体和乳剂是众所周知的适合用作疏水药物的载体的递送载剂的实施例。
该组合物可以经配制用于以任何合适的剂型向个体给予。该组合物可以经配制用于口服、面颊、鼻腔、经皮、肠胃外、注射、静脉内、皮下、肌肉、直肠或阴道给予。该组合物可以与佐剂一起配制呈合适的控释载剂，或作为药性持久的配方。
用于肠胃外给予的制剂包括准备用于注射的无菌溶液，准备仅仅在使用前与溶剂混合的无菌的干的可溶产品，包括皮下注射用片剂、准备用于注射的无菌悬浮剂、准备仅仅在使用前与载剂混合的无菌的干的不溶产品，和无菌乳剂。
抗-CD38-致弱干扰素α-2b融合结构可以用于，例如，抑制、降低、减小、阻止、或防止在它的表面表达CD38的细胞的增殖。在一些方面，抑制或降低在它的表面表达CD38的细胞的增殖的方法通常包括将表达CD38的细胞与有效抑制或降低该细胞增殖的量的抗-CD38-致弱干扰素α-2b融合结构接触。特异地结合CD38的该抗体可以是本文描述或例示的任何抗体。该致弱干扰素α2b可以包括IFN-α2bA145D或IFN-α2b A145G。该细胞可以是淋巴细胞、自身免疫性淋巴细胞、或肿瘤细胞，比如白血病细胞、多发性骨髓瘤细胞或淋巴瘤细胞。该抗-CD38-致弱干扰素α-2b融合结构可以与下列物质一起被包括在组合物中，例如，药学上可接受的载体和任选地一种或更多种助剂或赋形剂，包括本文描述或例示的任何这样的载体、助剂或赋形剂。该方法可以体外(in vitro)、间接体外(ex vivo)、体内(in vivo)或原位(in situ)进行。
抗-CD38-致弱干扰素α-2b融合结构也可以用于，例如，诱导、促进、或提高在它的表面表达CD38的细胞的凋亡。在一些方面，诱导在它的表面表达CD38的细胞的凋亡的方法通常包括经将表达CD38的细胞与有效诱导该细胞凋亡的量的抗-CD38-致弱干扰素α-2b融合结构接触。特异地结合CD38的抗体可以是本文描述或例示的任何抗体。该致弱干扰素α2b可以包括IFN-α2b A145D或IFN-α2b A145G。该细胞可以是淋巴细胞、自身免疫性淋巴细胞或肿瘤细胞，比如白血病细胞、多发性骨髓瘤细胞或淋巴瘤细胞。该抗-CD38-致弱干扰素α-2b融合结构可以与下列物质一起被包括在组合物中，例如，药学上可接受的载体和任选地一种或更多种助剂或赋形剂，包括本文描述或例示的任何这样的载体、助剂或赋形剂。该方法可以体外(in vitro)、间接体外(ex vivo)、体内(in vivo)或原位(in situ)进行。
抗-CD38-致弱干扰素α-2b融合结构也可以用于治疗具有肿瘤的个体，该肿瘤包括在它们的表面表达CD38的细胞和/或至少部分地由在它们的表面表达CD38的细胞所介导。在一些方面，治疗包括在它们的表面表达CD38的细胞的肿瘤的方法一般包括以有效治疗个体中肿瘤的量向需要它的个体给予抗-CD38-致弱干扰素α-2b融合结构。有效治疗可以包括，例如，抑制或降低该肿瘤中CD38-阳性细胞的增殖和/或诱导该肿瘤中CD38-阳性细胞的凋亡。特异地结合CD38的该抗体可以是本文描述或例示的任何抗体。该致弱干扰素α2b可以包括IFN-α2b A145D或IFN-α2b A145G。该抗-CD38-致弱干扰素α-2b融合结构可以与以下物质一起被包括在组合物中，例如，药学上可接受的载体和任选地一种或更多种助剂或赋形剂，包括本文描述或例示的任何这样的载体、助剂或赋形剂。
通过向血液给予组合物的结构可以向肿瘤给予该抗-CD38-致弱干扰素α-2b融合结构或包括这样的结构的组合物。可以给药该抗-CD38-致弱干扰素α-2b融合结构或包括这样的结构的组合物使得该结构通过血流扩散到和/或进入肿瘤细胞。该结构可以被肿瘤细胞内化。
提供了在肿瘤治疗中使用抗-CD38抗体或抗-CD38抗体-致弱干扰素α-2b融合结构。提供了使用抗-CD38抗体或抗-CD38抗体-致弱干扰素α-2b融合结构治疗肿瘤的方法。可以使用本文描述或例示的任何抗-CD38抗体或抗-CD38抗体-致弱干扰素α-2b融合结构。可以治疗的肿瘤包括，但是不局限于，AIDS相关癌症、听神经瘤、急性淋巴细胞白血病、急性骨髓性白血病、腺样囊性癌、肾上腺皮质癌、待发性髓样化生(agnogenic myeloidmetaplasia)、脱发、腺泡状软-组织肉瘤(alveolar soft-part sarcoma)、肛门癌、血管肉瘤、再生障碍性贫血、星形细胞瘤、共济-毛细管扩张、基底细胞癌(皮肤)、膀胱癌、骨癌、肠癌、脑干胶质瘤、脑和CNS肿瘤、乳腺癌、CNS肿瘤、类癌瘤、宫颈癌、儿童脑肿瘤、儿童癌症、儿童白血病、儿童软组织肉瘤、软骨肉瘤、绒毛膜癌、慢性淋巴细胞白血病、慢性骨髓性白血病、结肠直肠癌、皮肤T细胞淋巴瘤(cutaneous T-Cell lymphoma)、皮肤纤维肉瘤-隆突性、促结缔组织增生性-小-圆-细胞-肿瘤(desmoplastic-small-round-cell-tumor)、导管癌、内分泌癌、子宫内膜癌、室管膜癌、食道癌、尤文肉瘤(Ewing’s sarcoma)、外-肝胆管癌、眼睛癌、眼睛：黑色素瘤、成视网膜细胞瘤、输卵管癌、范可尼贫血(fanconi anemia)、纤维肉瘤、胆囊癌、胃癌、胃肠癌、胃肠-类癌-肿瘤、泌尿生殖器癌、生殖细胞肿瘤、妊娠-滋养层-疾病、胶质瘤、妇科癌、恶性血液病、毛细胞白血病、头颈部癌、肝细胞癌、遗传乳腺癌、组织细胞增多病、霍奇金氏病(Hodgkin’s disease)、人乳头瘤病毒、葡萄胎、血钙过多、下咽癌、眼内黑色素瘤、岛细胞癌、卡波西肉瘤(Kaposi’s sarcoma)、肾癌、朗格汉斯-细胞-组织细胞增多病(Langerhan’s-cell-histiocytosis)、喉癌、平滑肌肉瘤、白血病、佛美尼综合征(Li-Fraumeni syndrome)、唇癌、脂肪肉瘤、肝癌、肺癌、淋巴水肿、淋巴瘤、霍奇金淋巴瘤、非霍奇金淋巴瘤、男性乳腺癌、肾恶性横纹肌样瘤(malignant-rhabdoid-tumor-of-kidney)、成神经管细胞瘤、黑色素瘤、默克尔细胞癌(merkel cell cancer)、间皮瘤、转移癌、口腔癌、多发性内分泌瘤病、蕈样霉菌病、骨髓增生异常综合征、多发性骨髓瘤、骨髓增殖性疾病、鼻癌、鼻咽癌、肾胚细胞瘤、成神经细胞瘤、神经纤维瘤、奈梅亨断裂综合征(nijmegen breakage syndrome)、非-黑瘤皮肤癌、非-小-细胞-肺-癌-(NSCLC)、眼睛癌、食管癌、口腔癌、口咽癌、骨肉瘤、造口卵巢癌(ostomy ovarian cancer)、胰腺癌、鼻窦癌、甲状旁腺癌、腮腺癌、阴茎癌、外周型-神经外胚层-肿瘤、垂体癌、真性红细胞增多症、前列腺癌、罕见-癌-和-相关-疾病(rare-cancers-and-associated-disorders)、肾细胞癌、成视网膜细胞瘤、横纹肌肉瘤(rhabdomyosarcoma)、色素沉着综合征(Rothmund-Thomsonsyndrome)、唾腺癌、肉瘤、神经鞘瘤、西泽里综合征(Sezary syndrome)、皮肤癌、小细胞肺癌(SCLC)、小肠癌、软组织瘤、脊髓肿瘤、鳞状-细胞-癌-(皮肤)、胃癌、滑膜肉瘤、睾丸癌、胸腺癌、甲状腺癌、渡型-细胞-癌-(膀胱)(transitional-cell-cancer-(bladder))、渡型-细胞-癌-(肾脏-骨盆-/-输尿管)、滋养层癌、尿道癌、泌尿系统癌、uroplakins、子宫肉瘤、子宫癌、阴道癌、外阴癌、沃登斯通巨球蛋白血症(Waldenstrom’s-macroglobulinemia)和维尔姆斯肿瘤(Wilms’tumor)。在一个具体实施方式中，该肿瘤选自多发性骨髓瘤或非霍奇金淋巴瘤的组。
在优选的方面，该方法用于治疗需要它的个体中的多发性骨髓瘤、白血病或淋巴瘤。这样的方法可以进一步包括用维甲酸，比如全反式维甲酸，治疗该个体。在一些优选的方面，其中细胞表面相关抗原是CD38，肿瘤或癌症可以选自多发性骨髓瘤、非霍奇金淋巴瘤、慢性骨髓性白血病、慢性淋巴细胞白血病或急性骨髓性白血病。
抗-CD38-致弱干扰素α-2b融合结构可以与其它药物组合和/或用于添加到其它癌症治疗方案或形式，比如放射治疗或手术。当抗-CD38-致弱干扰素α-2b融合结构用于与已知治疗剂组合时，该组合可以依次地(连续地或间断一段时间不治疗)或同时地或作为混合物被给予。在癌症情况下，存在大量已知可以用于这个情况的抗癌剂。还考虑以组合形式治疗以包含用抗-CD38-致弱干扰素α-2b融合结构治疗，然后已知治疗，或用已知试剂治疗然后用抗-CD38-致弱干扰素α-2b融合结构治疗，例如，作为维持疗法。例如，在癌症治疗中，考虑抗-CD38-致弱干扰素α-2b融合结构可以与下列物质组合给予：烷化剂(比如二氯甲基二乙胺、环磷酰胺、苯丁酸氮芥(chlorambucil)、异环磷酰胺顺铂(ifosfamidecysplatin)，或包含铂的烷基化样试剂(platinum-containing alkylating-like agents)，比如顺铂(cisplatin)、卡铂(carboplatin)和奥沙利铂(oxaliplatin))、抗代谢物(比如嘌呤或嘧啶类似物或抗叶酸剂，比如咪唑硫嘌呤和巯嘌呤)、蒽环霉素(比如道诺霉素(Daunorubicin)、阿霉素(Doxorubicin)、表柔比星(EpirubicinIdarubicin)、戊柔比星(Valrubicin)、米托蒽醌(Mitoxantrone)或蒽环霉素(anthracycline)类似物)、植物碱(比如长春花生物碱或紫杉醇，比如长春新碱(Vincristine)、长春花碱(Vinblastine)、长春瑞滨(Vinorelbine)、长春地辛(Vindesine)、紫杉醇或多西他赛(Docetaxel))、拓朴异构酶抑制剂(比如I类和II类拓朴异构酶抑制剂)、足叶草毒素(Podophyllotoxin)(比如依托泊苷(etoposide)或替尼泊苷(teniposide))、或酪氨酸激酶抑制剂(比如甲磺酸伊马替尼(imatinibmesylate)、尼罗替尼(Nilotinib)、达沙替尼(Dasatinib))。
在治疗多发性骨髓瘤的情况下，抗-CD38-致弱干扰素α-2b融合结构可以与其它合适的疗法组合给予，比如利用给予类固醇比如地塞米松(dexamethasone)、蛋白酶体抑制剂(比如硼替佐米(bortezomib)或卡非佐米(carfilzomib))、免疫调节药物(比如萨利多安(thalidomide)、来那度胺(lenalidomide)或泊马度胺(pomalidomide))，或诱导化学疗法治疗个体，然后通过在使用或不使用其它化学治疗剂比如美法仑(Melphalan)盐酸盐或上面列出的化学治疗剂的情况下，自身造血干细胞移植。
在霍奇金淋巴瘤的治疗情况下，抗-CD38-致弱干扰素α-2b融合结构可以联合当前治疗方法被给予，比如ABVD(亚德里亚霉素(Adriamycin)(阿霉素)、博来霉素(bleomycin)、长春花碱和达卡巴嗪(dacarbazine))或Stanford V(阿霉素、博来霉素、长春花碱、长春新碱、氮芥、依托泊苷、强的松(prednisone))、或BEACOPP(阿霉素、博来霉素、长春新碱、环磷酰胺、甲基苄肼(procarbazine)、依托泊苷、强的松)。
在非霍奇金淋巴瘤或其他淋巴瘤的情况中，抗-CD38-致弱干扰素α-2b融合结构可以联合当前治疗方法被给予。批准用于非霍奇金淋巴瘤的药物实施例包括Abitrexate(甲氨蝶呤)、阿霉素PFS(阿霉素盐酸盐)、Adriamycin RDF(阿霉素盐酸盐)、Ambochlorin(苯丙酸氮芥(Chlorambucil))、Amboclorin(苯丙酸氮芥)、Arranon(奈拉滨(Nelarabine))、苯达莫司汀盐酸盐(Bendamustine Hydrochloride)、百克沙(Bexxar)(托西莫单抗(Tositumomab)和碘131托西莫单抗)、Blenoxane(博来霉素)、博来霉素、硼替佐米、苯丁酸氮芥、Clafen(环磷酰胺)、环磷酰胺、癌得星(Cytoxan)(环磷酰胺)、地尼白介素(Denileukin Diftitox)、DepoCyt(脂质体阿糖孢苷(Liposomal Cytarabine))、阿霉素盐酸盐、DTIC-Dome(达卡巴嗪)、脱叶亚磷(Folex)(甲氨蝶呤)、脱叶亚磷PFS(Folex PFS)(甲氨蝶呤)、拉曲沙(Folotyn)(普拉曲沙(Pralatrexate))、替伊莫单抗(IbritumomabTiuxetan)、Istodax(罗咪地辛(Romidepsin))、瘤可宁(Leukeran)(苯丁酸氮芥)、瘤可宁(Linfolizin)(苯丁酸氮芥)、脂质体阿糖孢苷、Matulane(甲基苄肼盐酸盐)、甲氨蝶呤、甲氨蝶呤LPF(甲氨蝶呤)、Mexate(甲氨蝶呤)、Mexate-AQ(甲氨蝶呤)、Mozobil(普乐沙福(Plerixafor))、奈拉滨(Nelarabine)、Neosar(环磷酰胺)、Ontak)(地尼白介素)、普乐沙福(Plerixafor)、普拉曲沙(Pralatrexate)、美罗华(利妥昔单抗(Rituximab))、利妥昔单抗、罗咪地辛(Romidepsin)、托西莫单抗和碘131托西莫单抗、Treanda(苯达莫司汀(Bendamustine)盐酸盐)、长春碱(Velban)(长春花碱硫酸盐)、万珂(Velcade)(硼替佐米)、和Velsar(长春花碱硫酸盐)、长春花碱硫酸盐、Vincasar PFS(长春新碱硫酸盐)、长春新碱硫酸盐、伏立诺他(Vorinostat)、泽娃灵(Zevalin)(替伊莫单抗)、Zolinza(伏立诺他)。用于治疗非霍奇金淋巴瘤的药物组合的实施例包括CHOP(C＝环磷酰胺，H＝阿霉素盐酸盐(羟基道诺霉素)，O＝长春新碱硫酸盐(Oncovin)，P＝强的松)；COPP(C＝环磷酰胺，O＝长春新碱硫酸盐(Oncovin)，P＝甲基苄肼盐酸盐，P＝强的松)；CVP(C＝环磷酰胺，V＝长春新碱硫酸盐，P＝强的松)；EPOCH(E＝依托泊苷，P＝强的松，O＝长春新碱硫酸盐(Oncovin)，C＝环磷酰胺，H＝阿霉素盐酸盐(羟基道诺霉素)；ICE(I＝异环磷酰胺，C＝卡铂，E＝依托泊苷)和R-CHOP(R＝利妥昔单抗，C＝环磷酰胺，H＝阿霉素盐酸盐(羟基道诺霉素)，O＝长春新碱硫酸盐(Oncovin)，P＝强的松)。
抗-CD38抗体或抗-CD38-致弱干扰素α-2b融合结构可以用于检测CD38-阳性细胞，包括CD38-阳性肿瘤细胞。在一些方面，它们可以用在检测从个体分离的组织标本中的CD38-阳性肿瘤细胞的方法中，该方法通常可以包括将抗-CD38抗体或抗-CD38-致弱干扰素α-2b融合结构与从个体分离的组织标本接触，和检测该抗体或结构和组织标本中的CD38-阳性细胞的复合体。该组织标本优选血液。该细胞可以是CD38-阳性B-细胞淋巴瘤细胞、多发性骨髓瘤细胞、非霍奇金淋巴瘤细胞、慢性骨髓性白血病细胞、慢性淋巴细胞白血病细胞、或急性骨髓性白血病细胞。该方法可以进一步包括将该组织样本从该个体中分离。
本公开还特载包括本文描述和例示的任何该抗体和抗-CD38-致弱干扰素α-2b融合结构的试剂盒。该试剂盒可以用于提供抗体和其它试剂用于诊断、基础研究或治疗方法中。
在一些方面，试剂盒包括抗-CD38-致弱干扰素α-2b融合结构，该结构任选包括在组合物中，该组合物包括药学上可接受的载体，和在一种或更多种抑制或降低在它的表面表达CD38的肿瘤细胞的增殖的方法，诱导在它的表面表达CD38的肿瘤细胞的凋亡的方法，和/或治疗包括在它们的表面表达CD38的细胞和/或由在它们的表面表达CD38的细胞介导的肿瘤的方法中使用该试剂盒的说明书。这样的方法可以是本文描述和例示的任何方法。该试剂盒可以包括药学上可接受的载体。该试剂盒可以包括一种或更多种药学上可接受的助剂和/或一种或多种药学上可接受的赋形剂。在该试剂盒中，该抗-CD38抗体可以是本文描述和例示的任何抗体，并且该致弱干扰素α-2b可以包括本文描述和例示的任何致弱干扰素α-2b。该结构可以包括在准备用于注射或静脉内给予的无菌溶液中，或可以包括准备用于仅仅在使用前与载体混合的无菌的、冻干的形式。
在一些方面，试剂盒包括抗-CD38抗体和在检测标本中的CD38-阳性细胞的方法中使用该试剂盒的说明书，该标本包括从个体分离的组织标本。该抗-CD38抗体可以是本文描述和例示的任何抗体。该抗体可以任选地被融合到致弱干扰素α-2b蛋白质上。
提供下面的实施例用于更详细地描述本公开。它们意在说明不是限制本公开。
实施例1
优化X355/02-HC-L0-IFN-α(A145D)IgG4
其它的抗-CD38-致弱IFN融合蛋白被记载在PCT申请号PCT/AU2012/001323中。这些包括在PCT申请中被指定为X355/02-HC-L0-IFN-α(A145D)IgG4的抗体结构(antibodyconstruct)。在本说明书中，X355/02-HC-L0-IFN-α(A145D)IgG4已经被重新命名为A02.1。该抗体的重链序列包括氨基酸序列SEQ ID NO:11，以及轻链序列包括氨基酸序列SEQ IDNO:12。A02.1的可变轻链(SEQ ID NO:14)与A02.1它的可变重链(SEQ ID NO:13)共表达，该A02.1它的可变重链(SEQ ID NO:13)在含有取代S228P(EU编号)(SEQ ID NO:3)的人IgG4恒定区上被格式化。这种抗体在本文被称为X02.1。A02.1包括与IFN-α2b的融合，而X02.1并不包括，尽管两种抗体具有相同的重链和轻链序列。
针对人胚系免疫球蛋白基因的数据库的BLAST研究(阿尔丘尔(Altschul)SF(1997)核酸研究(Nucleic Acids Res.)25:3389-3402)通过采用X02.1的可变重链的氨基酸序列进行。最接近的人胚系可变重链基因是IGHV4-61*01(SEQ ID NO:16)。X02.1VH和IGHV4-61*01的比对被显示在图2中。X02.1的可变重区与其最接近的胚系氨基酸序列相差8个氨基酸。为了降低X02.1的重链可变区的免疫原性，当它不同于胚系序列时，在残基处制备胚系氨基酸残基取代并且生成的抗体变体经测试用于抗CD38结合活性。
数个X02.1的重链变体亲代序列在图2中被详述了。这些重链可变区在IgG4S228P恒定区上被格式化并且与A02.1轻链共表达。表1a和表1b详述了经测试的变体序列连同如通过采用流式细胞术(flow cytometry)和表面等离子体共振(surface plasmonresonance)(SPR)所评估的它们结合人CD38的能力。简单地说，抗体链在CHO细胞中被短暂地共表达，且通过蛋白A色谱层析法纯化，如实施例5中所描述的。采用实施例5中描述的流动结合试验(Flow binding assays)评估变体。针对每个抗体获得的剂量响应曲线的EC50也被提供在表1a和1b中。
表1a
N/T–蛋白无法被纯化并且未被测试。
表1b
N/T–蛋白未被纯化或未被测试。
表1a中详述的变体的SPR结合与表1b中的那些变体的SPR结合分别地被评估。在SPR结合试验中，亲代抗体X02.1的KD(M)从2.7x 10-8到3.78x 10-10。流式细胞术结合试验显示了抗体X02.8、X02.11、X02.69和X02.71牢固地结合CD38阳性细胞系ARP-1。
具有上述氨基酸取代的抗体随后在通过结合到致弱IFN-α2b上的融合蛋白的情况中被探究(被连接到IFN时，称作A02，其中数字尾随小数代表具有X02名称的相同变体)。这些重链可变区在包括取代S228P的融合至A145D致弱IFN-α2b的IgG4恒定区上被格式化，并且在CHO或HEK细胞中与A02.1轻链共表达，如实施例5中所描述。成功地从细胞上清液纯化的蛋白接着在至细胞系ARP-1的流动结合试验中被测试。每个抗体的剂量响应曲线的EC50值被提供在表2中。所有抗体-致弱IFN融合结构经测试结合至CD38阳性细胞系ARP-1。观察到，重链变体X02.9(未融合至IFN)无法容易地被纯化，然而融合至IFN的相同变体(A02.9)被纯化。在一些情况下，当同等单克隆抗体呈现更难被表达和/或纯化时，致弱IFN融合蛋白能够被表达且被纯化。
表2
*在细胞培养基上清液中抗-CD38致弱IFN融合蛋白的量是通过由SPR的蛋白A捕获指示。通过SPR的CD38结合是指在350秒离解阶段(dissociation phase)后保留结合到表面的CD38的量。
采用A02.1可变轻链的氨基酸序列针对人胚系免疫球蛋白基因的数据库进行BLAST研究。最接近的人胚系可变轻链基因是IGLV5-37*01。A02.1VL和IGLV5-37*01的氨基酸序列比对被显示在图3中。这种比对说明了这些序列之间的12种氨基酸差异。
在X02.1可变轻链中进行数个氨基酸取代。这些取代被显示在图3中。如实例5中描述的，这些轻链可变区与X02.1可变重链的的共表达在CHO细胞中进行，该X02.1可变重链在含有取代S228P的IgG4恒定区上被格式化。
从CHO细胞上清液纯化的抗体随后在至CD38阳性细胞系ARP-1的基于流式细胞术的结合试验中被测试。表3详述了针对每个抗体获得的剂量响应曲线的EC50值。
表3
N/T–蛋白未被纯化或未被测试。
低结合–观察到最小的结合，不能满足EC50值。
*抗体在流动结合试验中针对H929细胞系被测试。经报道的值为EC50μg/mL。
抗体X02.96、X02.99、X02.101、X02.102、X02.103和X02.104牢固地被结合到CD38阳性ARP-1细胞系。X02.105能够牢固地结合到CD38阳性H929细胞系。
X02.1和A02.1的可变重链序列的氨基酸序列分析识别了能潜在地经历氧化或异构化的氨基酸。这些包括在D101处的潜在的异构化位点和在M(100C)处的潜在的氧化位点。为了移走潜在的异构化和氧化位点，进行氨基酸取代如下：D(101)E(SEQ ID NO:30)、M(100C)L(SEQ ID NO:29)和D(101)E和M(100C)L(SEQ ID NO:27)的组合(图2)。用如表4中所示的可变重链中这些氨基酸取代的组合制备抗体。抗体重链可变区与含有取代S228P的IgG4恒定区一起被格式化(formatted)，并且在CHO细胞中与A02.1轻链共表达。接着抗体通过蛋白A色谱层析法纯化，并且通过流式细胞术筛选用于结合到ARP-1细胞。获得的结合数据被显示在表4中。
表4
N/T–蛋白未被纯化或未被测试。
抗体X02.76和X02.77保持它们牢固的结合到ARP-1细胞系，表明去掉X02.1和A02.1重链中潜在的氧化和异构化位点的氨基酸取代对它们的CD38结合活性几乎没有影响。将这些取代组合以形成抗体X02.74，导致了没有采用实施例5中的协议纯化的抗体。
X02.1和A02.1的可变轻链序列的氨基酸分析鉴别了能够潜在地经历氧化或脱氨基(deamidation)的氨基酸。这些包括在N69处的潜在的脱氨基位点和在M89处的潜在的氧化位点。另外，假定的N连接的糖基化位点被预测存在于在位置N94的轻链的CDR3内。N连接的聚糖的存在能引起治疗性蛋白的多样性，使开发复杂化。为了去除这些潜在的问题，下述的点变体(point variants)被合成：N69A(SEQ ID NO:39)、M89L(SEQ ID NO:52)和M89I(SEQ ID NO:51)、N94T(SEQ ID NO:48)、N94Q(SEQ ID NO:38)、G95P(SEQ ID NO:50)和S96A(SEQ ID NO:45)(参见图3)。如表5中详述的，抗体通过在CHO细胞中重链和轻链的共表达被产生。抗体通过蛋白A色谱层析法纯化，并且通过流式细胞术筛选用于结合到ARP-1细胞。获得的结合数据被显示在表5中。
表5
N/T–蛋白未经纯化或测试。
低结合–观察到最小的结合，没有满足EC50或KD值。
X02.94结合CD38阳性细胞系ARP-1表明了取代M89L对CD38结合活性几乎没有影响。抗体X02.80中的取代N94Q移走了对如流式细胞术所测量的CD38结合活性(表5)具有最小影响的潜在的N连接的糖基化模体。移走该糖基化模序的其它取代导致不容易被纯化的抗体或显示减弱的到CD38阳性细胞系ARP-1的结合的抗体。虽然这种抗体(X02.81)不容易被纯化，但还是通过丙氨酸的取代移走了在位置69处的潜在的脱氨基位点。
包括X02.1可变重链变体的经测试的其它抗体被列举在表6中。这些重链可变区在含有S228P取代的IgG4恒定区上被格式化。这些重链在CHO细胞中与A02.1轻链共表达。抗体被表达且生成的抗体在基于流式细胞术的实验中经测试用于结合到CD38-阳性细胞ARP-1。除了T23K(SEQ ID NO:21；X02.68)之外，所有可变重链取代对在基于流式细胞术的实验中到CD38阳性细胞系ARP-1的结合具有最小的影响。
表6
N/T–抗体未被纯化或测试。
还制备了包含X02.1序列中其它轻链可变区取代的抗体。这些可变轻链与在含有取代S228P的IgG4恒定区上被格式化的X02.1重链组合并且在CHO细胞中被表达，如实施例5所描述的。用于制备这些抗体变体的重链和轻链的概括被提供在表7中。抗体X02.83、X02.85、X02.91、X02.82牢固地结合到CD38阳性细胞系ARP-1。
表7
N/T–蛋白未经纯化或测试。
低结合–观察到最小的结合，不满足EC50值。
***Δ表明存在于A02.1轻链中的该氨基酸从该序列被移走。
*基于通过SPR的蛋白A捕获含量的经估算的蛋白数值。
##在单独的实验中评估针对X02.107的SPR结合，其中亲代抗体X02.1的KD是2.7x10-8。亲代抗体X02.1在针对所有其它经测试的抗体的SPR结合试验中KD是3.78x10-10。
对CD38结合活性和X02变异抗体的纯化几乎没有影响的取代随后通过融合至A145D致弱IFN-α2b产生为有臂抗体(armed antibodies)。X02.1轻链取代被组合并且生成的变体在HEK293E细胞中与X02.1重链的点变体和组合变体(combinatorial variant)共表达，如表8中所列举的。这些抗体主要集中于移走潜在的X02.1轻链脱氨基位点、来自X02.1重链的CDR3氧化位点和通过在硅片上分析(Epibase，瑞士龙沙基团，英国)预测的X02.1重链的框架区3的假定的牢固的MHC II级结合肽(MHC Class II binding peptide)，图4。表8
表8中列举的抗体经分析用于蛋白表达和通过表面等离子体共振(SPR)的到CD38的结合。效价试验也通过采用取自转染细胞的细胞培养基上清液进行以评估这些抗-CD38致弱IFN融合蛋白中每者的相对活性，如实例5中概述的。获得的数据被提供在表9中。
表9
通过SPR的CD38结合是指在350秒解离阶段之后CD38保留结合到表面的量。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC(Annexin V-FITC)染色呈阳性。半胱天冬酶试验是指用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活细胞。N/A—没有获得；N/T—未被测试。
经测试的蛋白A02.12在膜联蛋白V、半胱天冬酶和细胞增殖试验中很好地表达且证明了效价。抗体A02.47中的取代N69T没有影响在膜联蛋白V或半胱天冬酶试验中的表达水平或效价，这暗示了移走这种脱氨基位点是可能的。取代N69T可被并入到本文的其它结构中以移走这种在生成的抗体的功能活性(functional activity)中具有最小损失的该假定的脱氨基位点。
实例2
在硅片上免疫原性分析A02.1轻链氨基酸序列
采用Epibase分析软件(瑞士龙沙基团，英国)在A02.1的轻链可变区氨基酸序列中鉴别假定的免疫原性表位。为了移走假定的免疫原性表位，取代被引到A02.1可变轻链中(图4)。具有较低的预测的免疫原性的轻链在HEK293E细胞中与A02.12重链可变区(SEQ IDNO:34)共表达，A02.12重链可变区(SEQ ID NO:34)在融合至A145D-致弱IFN的含有取代S228P的IgG4恒定区上被格式化。制备的抗体变体在图10中详述了。
表10
分析上述抗体的蛋白质表达、通过SPR的CD38结合、和采用细胞培养基上清液筛选(cell culture supernatant screen)的效价，，如实施例5中所描述的。这些实验的结果被详述在表11中。这些数据表明了降低经预测的抗体的免疫原性的一些残基取代产生了在膜联蛋白V、半胱天冬酶和细胞增殖试验中表达并且具有功能效价的抗-CD38-致弱IFN融合蛋白。
表11
通过SPR的CD38结合是指在350秒解离阶段之后CD38保留结合到表面的量。膜联蛋白V试验是指在用20nM抗体构造处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶试验是指用20nM抗体构造处理24小时之后细胞的半胱天冬酶激活。DNB—没有结合；N/T—未被测试。
实施例3
多重氨基酸取代产生了优化的A02.1变体
通过将如上文描述的改进抗-CD38抗体的免疫原性、可制备性或效价的取代组合到单一的基因结构中，高度地经优化的抗-CD38抗体和抗-CD38致弱IFN融合蛋白被获得。表12概括了此类组合的取代并且详述了在HEK293E细胞中共表达且随后经测试的重联和轻链组合。
表12
分析表12中描述的每个抗体的蛋白表达、通过SPR的CD38结合和采用细胞培养基上清液的效价，。生成的数据被提供在表13中。这些结果证明了在硅片上预测有益的组合的取代产生了一些在膜联蛋白V、半胱天冬酶和细胞增殖试验中表达且具有功能效价的抗-CD38致弱IFN融合蛋白。
表13
通过SPR的CD38结合是指在350秒解离阶段之后CD38保留结合到表面的量。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶试验是指用20nM抗体结构处理24小时之后半细胞的胱天冬酶激活。DNB—没有结合；N/T—未被测试。
实施例4
配对不同重链和轻链抗-CD38抗体
为了确定功能性抗-CD38-致弱IFN融合蛋白是否能被获得，来自PCT/AU2012/001323中描述的抗体X910/12-HC-L0-IFN-α(A145D)IgG4的重(SEQ ID NO:110)链和轻(SEQID NO:112)链以及来自PCT/AU2012/001323中描述的抗体X913/15-HC-L0-IFN-α(A145D)IgG4的重(SEQ ID NO:111)链和轻(SEQ ID NO:113)链以不同的组合彼此配对并且与上述实施例中描述的重链和轻链配对。重链和轻链的配对的总结被提供列举在表14中。
表14
分析每个制备的抗体的蛋白表达、通过SPR的CD38结合和采用细胞培养基上清液效价实验的效价，。这些实验的结果被呈现在表15a中。这些数据显示了配对来自不同抗体的重链和轻链产生了一些在膜联蛋白V、半胱天冬酶和细胞增殖试验中表达且具有功能效价的抗-CD38-致弱IFN融合蛋白。
表15a
通过SPR的CD38结合是指在350秒解离阶段之后CD38保留结合到表面的量。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶试验是指用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。DNB—没有结合。
选择的上述抗-CD38-致弱IFN融合蛋白被纯化且经分析用于在基于细胞的实验中结合CD38阳性细胞。另外，重复效价实验以提供更准确地测定每个抗-CD38-致弱IFN融合蛋白的相对活性。这些实验的结果被提供在表15b中。
表15b
流动结合是指被要求获得最大平均荧光强度的50％的抗体的浓度。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶试验是指用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。LB–低结合，不满足EC50值。*抗体在流动结合试验中针对H929细胞系被测试。报道的值是EC50μg/mL。
图5列举了共有可变重链(consensus variable heavy chain)以及图6列举了具有功能活性的A02.1相关构造的共有可变轻链。进一步设想，进行取代的组合，比如针对抗-CD38抗体X02.114、X02.115、X02.116、X02.117、X02.118、X02.119(图6)、X02.120、X02.121、X02.122、X02.123、X02.124、X02.125、X02.126或X02.127(图30)描述的那些。另外，上述抗-CD38抗体还可被构建为抗-CD38-致弱IFN融合蛋白并且针对功能活性被测试，如本文所描述的。
H929多发性骨髓瘤异种移植模型(H929multiple myeloma xenograft model)
A02.1体内效价先前在NCI-H929皮下多发性骨髓瘤模型中被测试，如实施例5中所描述的。A02.1被显示具有有效的抗肿瘤活性。PCT/AU2012/001323中显示了该数据。
如上所描述的，H929多发性骨髓瘤异种移植模型可被用于测试任何抗-CD38-致弱IFN融合蛋白的抗肿瘤活性。
致弱IFN对于肿瘤细胞系中有效的细胞凋亡和半胱天冬酶激活是必需的。
采用膜联蛋白V试验和半胱天冬酶试验，证明了有效的细胞凋亡活性和半胱天冬酶激活依赖于含有致弱IFN的抗-CD38-致弱IFN融合蛋白(表16a，图18)。在膜联蛋白V试验中，含有蛋白(A02.1和A02.6)的致弱IFN具有相比于不含有致弱IFN的蛋白(X02.1和X02.6)2倍活性。
表16a
膜联蛋白V试验是指在用20nM抗体结构处理24h之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶试验是指用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
实施例5
常规方法
制备HEK-293E细胞中的抗体和抗体-融合结构。编码蛋白结构(抗体和抗体-IFN-α2b相关的结构)的DNA质粒通过采用高速质粒马克西试剂盒(HiSpeed Plasmid Maxi Kit)(德国快而精公司(Qiagen)，巴伦西亚(Valencia)，CA)制备并且接着采用市场上可获得的转染试剂和OptiMEM介质(英杰公司，卡尔斯巴德，CA)被转染进入HEK293E细胞中(加拿大国家研究理事会(CNRC,)，蒙特利尔(Montreal)，加拿大)，该HEK293E细胞在补充有0.45％(w/v)D-(+)-葡萄糖(Sigma，卡斯尔山(Castle Hill)，NSW)，25μg/mL遗传霉素(英杰公司(Invitrogen)，卡尔斯巴德(Carlsbad)，CA)和1x GlutaMAX(英杰公司，卡尔斯巴德，CA)的F17合成培养基中生长。在提供有5％CO2和120rpm摇动的恒温箱中允许表达6天之后，培养基被分离且采用蛋白A Mab Select SuReTM琼脂糖小球(GE医疗保健(GE Healthcare)，皮斯卡塔韦(Piscataway)，新泽西(NJ))遭受亲和纯化。在pH 6.0，采用PD Midi-Trap G-25柱(GE医疗保健，皮斯卡塔韦，新泽西)或HiPrep26/10脱盐柱(HiTrap脱盐HiPrep 26/10脱盐)，经纯化的蛋白结构被缓冲液交换进入0.2M精氨酸盐酸盐、25mM柠檬酸、71.5mM氢氧化钠。接着经纯化的蛋白结构通过采用50kDa Amicon Ultra离心过滤器设备(密理博(Millipore)，比勒利卡(Billerica)，MA)被浓缩，然后通过读取280nm处的吸光度测定蛋白浓度。
在CHO细胞中制备抗体和抗体-融合结构。
编码蛋白结构(抗体和抗体-IFN-α2b相关的结构)的DNA质粒通过采用高速质粒马克西试剂盒(德国快而精公司，巴伦西亚，CA)制备并且接着通过采用市场上可获得的转染试剂和OptiPro SFMTM介质(英杰公司，卡尔斯巴德，CA)被转染进入在FreestyleTMCHO表达介质(Expression Medium)(英杰公司，卡尔斯巴德，CA)中生长的CHO细胞(瑞士龙沙集团)中。在提供有10％CO2和120rpm摇动的恒温箱中允许表达6天之后，培养基被分离且采用蛋白A Mab Select SuRe琼脂糖小球(GE医疗保健，皮斯卡塔韦，新泽西)遭受亲和纯化。在pH6.0，采用PD Midi-Trap G-25柱(GE医疗保健，皮斯卡塔韦，新泽西)或HiPrep 26/10脱盐柱(HiTrap脱盐HiPrep 26/10脱盐)，经纯化的蛋白结构被缓冲液交换进入0.2M精氨酸盐酸盐，25mM柠檬酸，71.5mM氢氧化钠。接着经纯化的蛋白结构通过采用50kDa Amicon Ultra离心过滤器设备(密理博，比勒利卡，MA)被浓缩，然后通过读取280nm处的吸光度测定蛋白浓度。
如通过表面等离子体共振(SPR)所测量的，抗-CD38-致弱IFN融合蛋白结合CD38。抗-CD38抗体和抗-CD38-致弱IFN融合蛋白结合人CD38的能力通过采用经制备的未纯化的转染细胞上清液与非特定的结合还原剂(GE医疗保健，皮斯卡塔韦，新泽西)7:1被测量。简单地说，采用BiacoreTM 3000或T200，利用氨基偶联，提供大约1500RU，蛋白A被固定到CM5研究级别感测器芯片(research grade sensor chip)的流动细胞(FC)1(FC1)和FC2(或者FC3和FC4)上。FC2(或FC4)在整个实验中被作为参照。在37o C在HBS-P+缓冲液(0.01M HEPES、0.15M NaCl、0.005％v/v表面活性剂P20、pH 7.4)中进行该实验。在流速20μl/分钟下，仅仅在含有蛋白的40μL上清液在FC1(或FC3)上通过之前，用10μL 50mM氢氧化钠再生两种流动细胞。30μL CD38(在运行缓冲液(running buffer)中10μg/mL)或30μL运行缓冲液在FC1和FC2上在5分钟解离时间(dissociation time)内被注射。两种表面用氢氧化钠再生两次。采用装备有机器的BIA评估软件(BIAevaluation software)获得了结果。Microsoft Excel被用于计算。针对每个样品，BIA评估软件自动地扣掉参照传感图，提供微量FC2-1(或FC4-3)。对每个抗体执行双重参考(double reference)，该抗体通过将具有CD38注射的传感图从具有空白运行缓冲液注射的传感图中扣掉被测试。蛋白A捕获是指从固定的时间点412.5s处的传感图测量得到的响应单位并且这相当于捕获在蛋白A表面上的蛋白含量。CD38结合是在507.5s处测量的响应单位并且是结合到蛋白捕获传感器的CD38含量的指示。CD38解离是在865.5s处测量的响应单位并且是在约300s解离阶段之后结合到蛋白捕获表面的CD38含量的指示。BIA评估被用于通过采用Langmuir 1:1方程式拟合传感图以得到平衡解离常数(KD)
蛋白A HPLC
采用连接到Agilent 1100色谱系统的POROS A/20 2.1x30mm Id柱(美国应用生物系统公司(Applied Biosystems))，通过蛋白A HPLC分析上清液。用PBS pH7.4平衡该柱并且用调节pH至2.2的PBS洗脱蛋白。标准曲线通过采用PBS中已知量的单克隆抗体得到。采用制造商的软件积分在波长215nm或280nm处的色谱图，并且曲线(AUC)下的面积针对生成的标准曲线经记录和修改以估算浓度。
流式细胞术结合抗体和抗-CD38-致弱IFN融合蛋白至人CD38阳性细胞系、ARP-1和H929。
多发性骨髓瘤细胞系ARP-1是来自阿肯色州医疗中心(小岩城，AK)大学骨髓瘤学院的巴特·巴洛奇MD、PhD院长的礼物。它被记载在Hardin J.et,al.(1994)Blood.84:3063-70。多发性骨髓瘤细胞系NCI-H929(H929)被购自ATCC(CRL-9068,盖士达(Gazdar),Blood 67:1542-1549,1986)。
在基于流式细胞术的试验中测试了抗体或抗体-干扰素结构结合人CD38-阳性骨髓瘤细胞系ARP-1或H929的能力。ARP-1细胞或H929细胞(5x 105，如台盼蓝不相容判断的)在96孔板中在黑暗中在冰上以不同浓度在50μL FACS缓冲液(PBS加上1％胎牛血清、FCS、0.2M HEPES、0.5M EDTA)与每个蛋白一起培养60分钟或与具有不相关的特异性蛋白结构的人IgG4单克隆抗体一起培养60分钟。细胞在含有山羊抗人IgG(goat anti-human IgG)(Fc-特异的，结合至异硫氰酸荧光素，FITC；Sigma-Aldrich，圣路易斯，MO)的50μL FACS缓冲液中培养30分钟之前，用FACS缓冲液洗涤3次。在用FACS缓冲液洗涤3次之后，细胞用50μL含有4％甲醛v/v的PBS固定并且在4℃在黑暗中培养16小时。在悬浮液中经培养的细胞采用额外的150μL FACS缓冲液稀释并且在采用FITC通道中的前向散射、侧面散射和荧光强度的FACSCanto II(BD生物科学，圣地亚哥，CA)上，通过流式细胞仪分析结合性。
报道的值是平均荧光强度(MFI)。
靶向实验
Daudi细胞增殖试验：该实验被用于定量IFN和抗体IFN融合蛋白结构对显示CD38的细胞的抗增殖活性。Daudi细胞表达CD38为细胞表面相关的抗原。采用来自Promega(麦迪逊(Madison)，威斯康星州(Wisconsin))的试剂
Cat#G7570测量细胞的存活能力。这是根据定量ATP测定培养中细胞的存活能力的基于冷光的实验。信号强度与微量滴定板孔中活细胞的数目呈比例。实验的细节如下所示：Daudi细胞(从ATCC，马纳萨斯，VA获得)在T75烧瓶(TPP，Trasadingen，瑞士，cat#90076)中被培养直至在具有10％牛胎儿血清(FBS；胎牛血清，洛根，UT cat#SH30070.03)的RPMI 1640(联发科技股份有限公司((Mediatech,Inc.)，马拉萨斯(Manassas)，VA，cat#10-040-CV)中优选的密度为0.5x 105和0.8x 105活细胞/mL之间。通过在400x g离心5分钟，滗析上清液并且在RPMI 1640+10％FBS中再悬浮细胞团块(cell pellet)收获细胞。接着计数细胞并且在RPMI 1640+10％FBS中密度被调整至3.0x 105细胞/mL。然后50μL细胞悬液被等分到96孔圆底组织培养板(此后简称为“实验板”)(TPP，cat#92067)的每个孔中。在一个分离的、无菌的96孔板上(此后简称为“稀释板”；科斯塔(Costar)，康宁公司(Corning)，NY cat#3879)，在RPMI1640+10％FBS中一式两份连续地稀释试验样品。50μL/孔从稀释板被转移到实验板。然后用5％CO2在37℃培养实验板4天。制造商提供的实验缓冲液和试验基质的混合物(此后被称为“
试剂”，根据制造商的说明书混合的)以100μL/孔被添加到实验板。摇动该板两分钟。
接着，100μL/孔从实验板被转移到96孔扁平的底部白色的不透明的板(此后简称为“分析板(assay plate)”；BD生物科学(BD Biosciences)，Franklin 5Lakes，NJ cat#353296)。接着，分析板上的内容物被允许在黑暗中在室温下稳定15分钟。在光度测定通道(luminometry channel)上，在Victor 3V Multilabel Counter(珀金埃尔默(PerkinElmer)，沃尔瑟姆(Waltham)，MA，model#1420-041)上读取该板并且测量冷光(luminescence)。结果被显示为“相对荧光单位”(RLU)。使用采用非-线性回归和三个参数曲线拟合，利用Prism 5(Graphpad，圣地亚哥(San Diego)，CA)分析数据以确定曲线的中点(EC50)。
ARP-1细胞增殖试验：该实验被用于定量IFN和抗体-IFN融合蛋白结构针对CD38抗原阳性细胞的抗增殖活性。ARP-1细胞表达CD38为细胞表面相关的抗原。采用来自Promega(麦迪逊，威斯康星州)的试剂
Cat#G7570测量细胞的存活能力。这是通过定量ATP测定培养中细胞存活能力的基于冷光的实验。该信号强度与微量滴定板孔中活细胞数成比例。
实验的细节如下所示：ARP-1细胞在T175烧瓶(科斯塔，康宁公司，NY Lakes，NJ，cat#CLS431080)中经培养直至在具有10％牛胎儿血清(FBS；AusGeneX，Molendinar，QLD，澳大利亚cat#FBS500S)的RPMI 1640(美国生命技术公司，马尔格雷夫，VIC，cat#11875-093)中优选的密度为2.0x 105和2.0x 106活细胞/mL之间。通过在400×g离心5分钟，滗析上清液并且在RPMI 1640+10％FBS中再悬浮细胞团块收获细胞。接着细胞经计数并且在RPMI 1640+10％FBS中密度被调整至2.0x 105细胞/mL。然后50μL细胞悬浮液被等分到96孔扁平的底部白色不透明板(此后简称为“实验板”；科斯塔，康宁公司，NY Lakes，NJ，cat#CLS3917)的每个孔中。在一个分离的、无菌的96孔板上(此后简称为“稀释板”；科斯塔，康宁公司，NYcat#3879)，在RPMI 1640+10％FBS中一式两份连续地稀释试验样品。随后地，50μL/孔从稀释板被转移到实验板。然后用5％CO2在37℃培养实验板4天。每个实验板包括作为相对对照(relative control)的亲代抗体IFN结构(parental antibody IFN construct)。
制造商提供的实验缓冲液和实验基质的混合物(根据制造商的说明书混合的
试剂)以100μL/孔被添加到实验板。摇动该板两分钟。然后，分析板上的内容物被允许在黑暗中在室温下稳定15分钟。在光度测定通道上，在FLUOstar Galaxy板阅读器(BMG Labtech，达拉谟(Durham)，NC)上读取该板并且测量冷光。使用采用非线性回归和三个参数曲线拟合，利用Prism 5(Graphpad，圣地亚哥，CA)分析数据以确定曲线的中点(EC50)。
膜联蛋白V试验：通过在400x g离心5分钟，滗析上清液且在RPMI 1640+10％FBS中再悬浮细胞团块获得H929细胞。接着计数细胞并且在RPMI 1640+10％FBS中密度被调整至1.0x 106细胞/mL。然后，50μL细胞悬浮液被等分到96孔圆底透明的板(此后被称为“实验板”；科斯塔，康宁公司，NY cat#CL3799)的每个孔中。在一个分离的、无菌的96孔板(此后被称为“稀释板”；科斯塔，康宁公司，NY cat#CL3799)上，试验样品在RPMI 1640+10％FBS中一式四份(in quaduplicate)稀释至40nM。随后地，50μL/孔从稀释板被转移到实验板。然后用5％CO2在37℃培养该实验板24小时。接着细胞在400×g离心5分钟，滗析上清液，并且在100μL含有膜联蛋白V-FITC(1/200)和7-AAD(1/50)的HEPES缓冲液中再悬浮。接着细胞在室温下被培养15分钟并且随后通过在采用前向散射、侧向散射、FITC和PerCP-Cy5.5通道的FACSCanto II(BD生物科学，圣地亚哥，CA)上的流式细胞术分析膜联蛋白V和7-AAD染色。膜联蛋白V阳性细胞是指在用20nM抗体结构处理24小时之后通过膜联蛋白V-FITC染色呈阳性的并且被表达为相对于未处理的细胞的倍数变化的细胞。
半胱天冬酶实验：激活的半胱天冬酶2、3、6、7、8、9、10在用试验抗体(testantibodies)处理之后，用来自罗氏公司(Roche)(西萨塞克斯郡(West Sussex)，英国(UK))的试剂均相半胱天冬酶实验(Homogeneous Caspases Assay)，荧光的Cat#12236869001测量。实验的细节如下。
表达高水平CD38的ARP-1细胞在T175烧瓶(科斯塔，康宁公司，NY，cat#CLS431080)中经培养直至在具有10％FBS(AusGeneX，Molendinar，QLD，澳大利亚cat#FBS500S)的RPMI1640(美国生命技术公司，马尔格雷夫，VIC，cat#11875-093)中优选的密度在2.0x 105和2.0x 106活细胞/mL之间。通过在400x g离心5分钟，滗析上清液且在RPMI 1640无酚红(美国生命技术公司，马尔格雷夫，VIC，cat#11835-030)+10％FBS中再悬浮细胞团块收获细胞。接着计数细胞并且在RPMI1640无酚红+10％FBS中密度被调整至2.0x 105细胞/mL。然后，50μL细胞悬浮液被等分到96孔扁平的底部的具有黑色壁的透明的底板(随后简称为“实验板”；科斯塔，康宁公司，NY cat#CLS3603)的每个孔中。在一个分离的、无菌的96孔板(此后简称为“稀释板”；科斯塔，康宁公司，NY cat#3799)上，试验样品在RPMI 1640无酚红+10％FBS中一式四份被稀释至40nM。随后50μL/孔从稀释板被转移到实验板。然后，用5％CO2在37℃培养实验板24小时。制造商提供实验缓冲液被添加到制造商提供的基质并且根据制造商的说明书混合以制备“基质溶液”。接着，100μL该基质溶液被添加到分析板的每个孔。摇动该板2分钟。接着该板在室温下在黑暗中培养15分钟并且最终在具有激发滤光片470-500nm和发射滤光片500-560nm的FLUOstar Galaxy板阅读器(BMG Labtech，达拉谟(Durham)，NC)上读取以及冷光被测量且被表示为相对于未处理的细胞的倍数变化。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
脱靶实验
iLite基因报告实验(iLite gene reporter assay)：“脱靶”iLite实验(PBL干扰素来源(PBL Interferon Source)，皮斯卡塔韦(Piscataway)，NJ，Cat#51100)被进行，大部分如制造商所描述的，其中添加了人IgG阻断步骤。iLite细胞系由制造商描述为“来源于市场上可获得的前-单核人细胞系(pro-monocytic human cell line)的稳定的转染细胞系，该前-单核人细胞系具有在细胞表面上表达MHC II级抗原，尤其人淋巴细胞抗原(HLADR)的特点”。该细胞系含有稳定地转染的荧光素酶基因，该荧光素酶基因的表达是由干扰素-响应元件(interferon-response element)(IRE)驱动，该干扰素-响应元件允许根据冷光输出量(luminescence output)定量干扰素活性。制造商提供的iLite板(此后简称为分析板)和稀释剂从-80℃冷冻库被移走并且被允许平衡到室温。然后，50μL稀释剂被添加到分析板的每个孔。制造商提供的报告细胞(reporter cell)的小瓶从-80℃冷冻库被移走并且在37℃水溶中解冻。然后，25μL等份细胞被分配到分析板的每个孔中。接着，经稀释到RPMI 1640+10％FBS(Sigma化学品，圣路易斯，MO；cat#I4506)中的12.5μL 8mg/mL人IgG被添加到每个孔。内容物经混合且在37℃下培养15分钟。在分离的“稀释板”上，试验样品在RPMI 1640+10％FBS中一式两份连续地经稀释。接着12.5μL试验样品从稀释板转移到分析板。接着用5％CO2在37℃培养分析板17小时。制造商提供的实验缓冲液和基质从-80℃冷冻库被移走并且被允许平衡至室温2小时。制造商提供的实验缓冲液被添加到制造商提供的基质小瓶并且根据制造商的说明书很好地混合以制备“冷光溶液(luminescence solution)”。然后100μL冷光溶液被添加到分析板的每个孔。摇动该板2分钟。接着该板在室温下在黑暗中被培养5分钟并且最终在光度通道上，在Victor 3V Multilabel Counter上读取，以及该冷光经测量且被表示为RLU。用所描述的用于“靶向(Daudi)试验(on-target(Daudi)assay)”的Graphpad Prism5分析数据。为了测试iLite试验中的抗-CD38抗体-IFN融合蛋白结构，制造商提供的稀释剂被补充有0.25mg/mL抗-CD38抗体(相同的抗体克隆被测试为抗体-IFN融合蛋白结构以阻断任何抗-CD38抗体-IFN融合蛋白结构结合在iLite细胞上被表达的CD38)。
HEK-BlueTM脱靶实验(HEK-BlueTM Off-target assay)：实验被用于通过采用HEK-BlueTMIFN-α/β细胞系(InvivoGen，圣地亚哥，CA)定量抗体IFN融合结构结合干扰素-α/β受体(IFNAR)的能力。大部分如HEK-BlueTM IFN-α/β细胞系的制造商所描述的，进行该“脱靶(HB-IFN)试验”。HEK-BlueTMIFN-α/β细胞专门地设计以监测由I类IFN诱导的JAK-STAT通路的激活。通过将人STAT2和IRF9基因引入到HEK293细胞中生成该细胞，以获得完全地激活的I类IFN信号通路。该HEK-BlueTMIFN-α/β细胞在ISG54启动子的控制下稳定地表达报告基因，分泌型胚胎碱性磷酸酶(SEAP)。ISG54是熟知的经由I类IFN通过ISRE依赖机理激活的ISG。经IFN-α或IFNβ刺激，HEK-BlueTMIFN-α/β细胞激活JAK-STAT通路并且接着表达SEAP报告基因。SEAP被分泌到介质中并且采用比色试剂QUANTI-BlueTM(colorimetric reagentQUANTI-BlueTM)能够被定量。简单地说，HEK-Blue IFNα-/β细胞(Invivogen，圣地亚哥CAcat#hkb-ifnab)被解冻并且在DMEM介质(联发科技，马拉萨斯VA，cat#10-013-CV)+已经被加热灭活的10％FBS(胎牛血清(Hyclone)，洛根(Logan)UT，cat#SH30070.03)(HI FBS)中被培养。当细胞达到60-80％聚集时，用细胞剥离器(联发科技，cat#25-056-Cl)解散它们。细胞在DMEM+HI FBS中被洗涤两次并且被计数。细胞在DMEM+HI FBS中被调整至3.3x 105活细胞/mL并且150μL被等分到扁平的底部96孔组织培养板(此后简称为“实验板”)的每个孔中。然后，50μL在DMEM+HI FBS中稀释的IFN-α2b或融合蛋白结构被添加到每个孔。在37o C 5％CO2培养该板16-24小时。根据制造商的用法说明书，制备QUANTI-Blue(Invivogen,cat#rep-qb1)。QUANTI-Blue(150μL)被等分到扁平的底板(此后简称为“分析板”)的每个孔中。接着来自实验板的每个孔中的50μL上清液被转移到分析板。接着分析板在37o C被培养1-3小时。在来自珀金埃尔默(Perkin-Elmer)的型号1420-41Victor 3V Multilabel Counter上读取分析板在630nm的吸光度。使用Graph Pad Prism分析数据。
H929异种移植模型
不同剂量的A10.38和A10.0抗-CD38-致弱IFN-α融合蛋白结构相比非-CD38-靶向的融合蛋白结构对骨髓瘤肿瘤生长的影响。对于这些比较，采用了NCI-H929皮下多发性骨髓瘤模型(NCI-H929s.c.multiple myeloma model)。
多发性骨髓瘤细胞系NCI-H929(ATCC CRL-9068，盖士达(Gazdar)，Blood67:1542-1549,1986)在免疫功能不全的(SCID)小鼠中被皮下种植。
用50％MatrigelTM中的1x 107NCI-H929肿瘤细胞在侧腹中皮下地注射8到12周大的CB.17SCID小鼠。当平均肿瘤大小达到170-350mm3时，小鼠被分成每7只小鼠为一组的4个组并且在时间零点(T0)开始治疗。通过腹腔内注射(i.p.)给予所有治疗一周两次持续3周(由图表下的横杠表示)。除了载剂组(vehicle group)之外，所有化合物的剂量为100μg/剂量(约4.5mg/kg)。通过卡尺测量，每周两次测量肿瘤体积。最终点是肿瘤体积2,000mm3。
不同剂量的A02.6、A10.0和A10.38抗-CD38-致弱IFN-α融合蛋白结构相比于载剂对骨髓瘤肿瘤生长的影响。对于这些比较，采用了NCI-H929皮下多发性骨髓瘤模型。
多发性骨髓瘤细胞系NCI-H929(ATCC CRL-9068,盖士达,Blood 67:1542-1549,1986)在免疫功能不全的(SCID)小鼠中被皮下种植。
用50％基底膜基质(Matrigel)中的1x 107NCI-H929肿瘤细胞，在侧腹中皮下注射8到12周大的CB.17SCID小鼠。当平均肿瘤大小达到90mm3时，小鼠被分成每5只小鼠为一组的4个组并且在时间零点(T0)治疗开始。通过腹腔内注射(i.p.)给予所有治疗一周两次持续3周(由图表下的横杠表示)。除了载剂组之外，所有化合物的剂量为100μg/剂量(约4.5mg/kg)。通过卡尺测量，每周两次测量肿瘤体积。
实例6
具有可供选择的恒定区的抗-CD38-致弱IFN融合蛋白
A02.12包括抗-CD38-致弱IFN融合蛋白，其中该蛋白的恒定区是HC-L0-IFN-α(A145D)IgG4(SEQ ID NO:9)。该抗体的重链可变区在融合至A145D致弱IFN-α2b(SEQ IDNO:10)的IgG1恒定区上被再格式化。该重链与X02.107(SEQ ID NO:65)的轻链在HEK293E细胞中共表达产生了抗体A02.112。采用基于流式细胞术的CD38-结合实验和效价实验的抗体A02.12和A02.112的比较证明了其它的抗体恒定区，比如人IgG1也可被使用，产生了抗体-致弱IFN融合蛋白具有有效的生物学活性等同于采用人IgG4恒定区产生的有效的生物学活性(表16b)。
表16b
*抗体在针对H929细胞系的流动结合试验中被测试。报道的值是EC50μg/mL。膜联蛋白V试验是指细胞经20nM的抗体结构处理24小时之后由膜联蛋白V-FITC染色呈阳性。半胱天冬酶试验是指经20nM的抗体结构处理20小时之后细胞的半胱天冬酶激活。N/T–未被测试。
实例7
人源化R5D1、R5E8和R10A2可变区
起源于鼠的抗-CD38抗体R5D1、R5E8和R10A2被描述在PCT/AU2012/001323中并且经选择用于人源化。如美国公开号2003/0039649中所记载的，这些抗体的可变区被超人源化。简单地说，通过检查它们各自的氨基酸序列，标准结构被指定给每个啮齿动物的重链和轻链。R10A2被指定标准结构2-1-1/1-2(VL/VH)，R5E8被指定标准结构4-1-1/1-2以及R5D1被指定标准结构2-1-1/1-2。相同的标准结构的人胚系序列被用作用于移植供体CDR(donorCDR)的受体骨架(acceptor framework)。含有氨基酸取代的生成的超人源化抗体基因的变体也被设计，该氨基酸取代在它们的序列中被认为有可能对于维持它们的结合活性重要的位置。不同的重链超人源化可变区(heavy chain superhumanized variable region)被显示在图7中。不同的轻链超人源化可变区被显示在图8中。
重链可变区序列被亚克隆至含有人IgG4恒定区的载体pEE6.4中，该人IgG4恒定区具有取代S228P，融合至A145D致弱IFN-α2b(SEQ ID NO:9)。轻链可变区被亚克隆至含有人kappa恒定区(human kappa constant region)(SEQ ID NO:5)的载体pEE12.4中。如先前所描述的，通过在CHO细胞中pEE6.4中的重链和pEE12.4中的轻链共表达制得抗体。表17概括了被用于制备每个超人源化基于5D1的蛋白的重链和轻链配对。表18详述了用于生成的超人源化基于5E8的蛋白的重链和轻链配对，而被用于生成超人源化基于10A2的蛋白的轻链和重链配对被提供在表19中。通过生成的CHO转染上清液的BIAcoreTM分析，进行超人源化抗体的单稳态平衡解离常数(KD)分级(One-shot equilibrium dissociation constant(KD)ranking)。该方法被用于确定该抗体是否表达(蛋白A捕获)并且具有结合人CD38活性的水平。
表17
DNB–没有结合。N/A–未获得。
表18
DNB–没有结合。N/A–没有获得。
表19
DNB–没有结合。
DNE–没有表达。
对于人源化抗体-5D1、5E8和10A2的每个族，数个人源化的重链和轻链组合没有表达蛋白或结合人CD38。遍及人源化抗体的全部3个族的相当大数量的抗体表达并且结合人CD38，其中具有在纳摩尔(nM)范围内的平衡解离常数。具有共同轻链的A10A2.53和A10A2.25经选择用于进一步优化。A10A2.53改称为A10.0，A10A2.25改称为A10.38。
实例8
改进的A10.0变体
通过改变可变的重和/或轻链序列优化A10.0抗体，具有对抗体的生物物理和在硅片上的免疫原性产生积极影响的同时对抗体的功能活性产生最小影响的目的。
A10.0重链和轻链的在硅片上的免疫原性分析
采用Epibase软件包，做出A10.0重链和轻链可变区在硅片上的免疫原性分析。数个氨基酸取代被引到A10.0重链和轻链可变区中以移走潜在的免疫原性表位。制得的与人源化重链(SEQ ID NO:156)比对的重链可变区变体的氨基酸序列比对被显示在图9中。与人源化轻链(SEQ ID NO:161)比对的轻链可变区变体的氨基酸比对被显示在图10中。重链和轻链变体在HEK293E细胞中共表达以产生蛋白的细节被概括在表20中。
表20
采用表20中概述的重链和轻链配对生成的每个抗体经评估用于蛋白表达水平和通过SPRCD38的结合。另外，采用细胞培养基上清液进行效价实验以评估这些抗-CD38抗体-致弱IFN融合蛋白中每者的相对功能活性，表21。
表21
通过SPR的CD38结合是指在350秒分离阶段之后CD38保留结合到表面上的量。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
DNB–没有结合；N/T-未被测试；否IC50–效价不满足IC50值。
分析A10.0可变重链和轻链序列的氨基酸序列鉴别数个潜在的脱氨基位点和一个潜在的氧化位点。制备可变重链取代N98Q以从重链SEQ ID NO:197的CDR3移走脱氨基位点。含有CDR2取代N53Q的A10.0可变轻链(SEQ ID NO:198)的进一步变体被生成以移走这种假定的脱氨基位点。通过在这种位置的氨基酸取代还改变轻链CDR3内的M89，具有去除这种潜在的氧化位点和降低这种轻链区域的预测的免疫原性的组合目的。这些取代，连同共表达以制备每个抗-CD38-致弱-IFN融合蛋白的重链和轻链配对被详述在表22中。
表22
采用表22中概述的重链和轻链配对生成的每个抗体经评估用于蛋白表达水平和通过SPR的CD38结合。另外，采用细胞培养基上清液进行效价实验以评估这些抗-CD38抗体-致弱IFN融合蛋白中每者的相对功能活性，如表23中所示。
表23
通过SPR CD38结合是指在350秒分离阶段之后CD38保留结合到表面上的量。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
实例9
生成改进的A10.38变体
A10.0和A10.38具有共同的轻链。优化的A10.0的轻链序列与A10.38抗体的重链配对，具有对抗体的生物物理和在硅片上的免疫原性性能产生积极影响而对功能活性具有最小影响的目的。表24描述了显示了重链和轻链的变化和配对的概要。
表24
上述抗体的每者经评估用于蛋白表达水平和通过SPR的CD38结合。采用细胞培养基上清液进行效价实验以评估这些抗-CD38抗体-致弱IFN融合蛋白中每者的相对功能活性，表25。
表25
通过SPR的CD38结合是指在350秒分离阶段之后CD38保留结合到表面上的量。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
N/T–未被测试。
减弱的IFN对于肿瘤细胞系中有效的细胞凋亡和半胱天冬酶激活是必需的
采用实例5中详述的膜联蛋白V、半胱天冬酶和细胞增殖试验，比较抗-CD38抗体A10.0(致弱IFN融合)和X10.0(没有融合)的相对效价。还比较A10.38和X10.38的相对效价，表26。
表26
膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
这些数据证明了由抗体A10.0和A10.38分别相对于X10.0和X10.38显示的有效细胞凋亡活性使致弱IFN融合的存在成为必需。没有观察到不具有减弱的IFN的抗体的抗增殖活性。
来自具有功能活性的蛋白的重链可变区的共有序列比对被显示在图11中。来自具有功能活性的蛋白的轻链可变区的共有序列比对被显示在图12中。进一步设想，进行取代的组合，比如针对抗-CD38抗体X10.60、X10.61、X10.62、X10.63、X10.64、X10.65、X10.66、X10.67、X10.68、X10.69、X10.70、X10.71、X10.72、X10.73、X10.74、X10.75、X10.76、X10.77、X10.78、X10.79、X10.80、X10.81、X10.82、X10.83、X10.84、X10.85、X10.86、X10.87、X10.88、X10.89、X10.90、X10.91、X10.92、X10.93、X10.94、X10.95、X10.96、X10.97、X10.98、X10.99、X10.100、X10.101、X10.102、X10.103、X10.104、X10.105、X10.106、X10.107、X10.108、X10.109、X10.110、X10.111、X10.112、X10.113、X10.114、X10.115、X10.116、X10.117、X10.118、X10.119、X10.120、X10.121、X10.122、X10.123、X10.124、X10.125、X10.126、X10.127、X10.128、X10.129、X10.130、X10.131、X10.132、X10.133、X10.134、X10.135、X10.136、X10.137、X10.138、X10.139、X10.140、X10.141、X10.142、X10.143、X10.144、X10.145、X10.146、X10.147描述的那些(图11、图12)。另外，上述抗CD38抗体还被构建为抗-CD38-致弱IFN融合蛋白且针对如本文所描述的功能活性被测试。
H929多发性骨髓瘤异种移植模型
10A2变体A10.0和A10A2.0的体内效价在NCI-H929皮下小鼠多发性骨髓瘤模型中被评估，图27。在这种模型中，两者均被显示具有有效的抗肿瘤活性。此类模型能被用于测试如本文所描述的其它蛋白结构的抗肿瘤活性。
10A2变体的脱靶活性
10A2变体A10.0、A10.38、A10A2.37和A10A2.39相比于融合至野生型和致弱干扰素145D的亲代A10A2.0嵌合抗体的脱靶活性在iLite报告基因实验和/或HEK Blue实验中被评估并且被显示在图28和图29中。EC50值被提供在图28和图29中。该脱靶活性确定了干扰素的致弱性和被靶向CD38的抗体以恢复功能的需要。
针对A10.0和相关结构的进一步体内功效数据
选择的上述抗-CD38-致弱IFN融合蛋白经纯化并且分析用于在基于细胞的试验中结合CD38阳性细胞。另外，重复效价实验以更准确地确定这些抗-CD38-致弱IFN融合蛋白中每者的相对活性。实例5描述了这些不同实验的方法。这些实验中每者的结果被提供在表27中。
表27
在H929细胞系中确定流动结合。膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。
具有可供选择的恒定区的抗-CD38-致弱IFN融合蛋白
A10.0包括抗-CD38-致弱IFN融合蛋白，其中蛋白的恒定区是HC-L0-IFN-α(A145D)IgG4(SEQ ID NO:9)。采用基因合成，该蛋白的恒定区被替换为HC-L0-IFN-α(A145D)IgG1(SEQ ID NO:10)，与A10.0轻链(SEQ ID NO:161)配对，并且被给予名称A10.59。该蛋白被表达并且在功能实验中被发现是有效的(表28)。虽然在上述实施例中被测试的大多数蛋白被结建到人IgG4恒定区上，但是这些数据证明了其它的抗体恒定区，比如人IgG1，也可以被使用，最终的抗体-致弱IFN融合结构具有有效生物活性相当于利用人IgG4恒定区的结构。
表28
膜联蛋白V试验是指在用20nM抗体结构处理24小时之后细胞由膜联蛋白V-FITC染色呈阳性。半胱天冬酶实验是指在用20nM抗体结构处理24小时之后细胞的半胱天冬酶激活。N/T是未被测试，*用细胞培养基上清液评估，从细胞增殖试验获得的数据。
表29列举了针对本文描述的每种抗体的可变重链、可变轻链和恒定区的配对。表30列举了在公开内容中使用的序列，AA是指氨基酸(序列型)以及DNA是指多核苷酸(序列型)。
表29
表30
该公开内容并不局限于上述描述和例示的实施方式，但是能够在本申请权利要求的范围内变化并且修改。
序列表
<110> 瑟法隆澳大利亚有限公司（Cephalon Australia Pty Ltd）
<120> 抗-CD38 抗体, 抗-CD38 抗体结构和它们的用途
<130> 185704-3015 (CAP572 WO)
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<170> PatentIn version 3.5
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Leu Pro Arg Trp Arg Gln Gln Trp Ser Gly Ser Gly Thr Thr Ser Arg
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Pro Glu Met Arg His Val Asp Cys Gln Ser Val Trp Asp Ala Phe Lys
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Asp Asp Leu Thr Trp Cys Gly Glu Phe Asn Thr Phe Glu Ile Asn Tyr
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Gln Ser Cys Pro Asp Trp Arg Lys Asp Cys Ser Asn Asn Pro Val Ser
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Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
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Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
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Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
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Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
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Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
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Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
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Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
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Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
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Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
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Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
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Leu Arg Ser Lys Glu
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Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
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Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
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Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
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Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
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Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
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Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
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Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
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Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
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Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
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Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
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Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
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Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
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Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
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Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
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Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
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Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
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Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
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Leu Ser Leu Ser Leu Gly Lys Cys Asp Leu Pro Gln Thr His Ser Leu
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Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
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Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
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Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
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Cys Ala Trp Glu Val Val Arg Asp Glu Ile Met Arg Ser Phe Ser Leu
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Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
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Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
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Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
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Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
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Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
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Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
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His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
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Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
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Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
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Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
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Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
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Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
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Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
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Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
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Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Cys Asp Leu Pro Gln Thr
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His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg
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Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe
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Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro
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Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys
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Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr
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Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly
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Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala
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Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys
450 455 460
Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Asp Glu Ile Met Arg Ser
465 470 475 480
Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490 495
<210> 11
<211> 121
<212> PRT
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Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
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Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
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Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
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Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
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Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
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Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
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Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
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Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
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Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
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Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
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Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
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Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
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Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
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Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
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Leu Thr Val Leu Gly Gln Pro Lys Ala Ala Pro Ser Val Thr Leu Phe
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Pro Pro Ser Ser Glu Glu Leu Gln Ala Asn Lys Ala Thr Leu Val Cys
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Leu Ile Ser Asp Phe Tyr Pro Gly Ala Val Thr Val Ala Trp Lys Ala
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Asp Ser Ser Pro Val Lys Ala Gly Val Glu Thr Thr Thr Pro Ser Lys
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Gln Ser Asn Asn Lys Tyr Ala Ala Ser Ser Tyr Leu Ser Leu Thr Pro
180 185 190
Glu Gln Trp Lys Ser His Arg Ser Tyr Ser Cys Gln Val Thr His Glu
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Gly Ser Thr Val Glu Lys Thr Val Ala Pro Thr Glu Cys Ser
210 215 220
<210> 13
<211> 121
<212> PRT
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Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 14
<211> 117
<212> PRT
<213> 智人
<400> 14
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 15
<211> 121
<212> PRT
<213> 智人
<400> 15
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 16
<211> 99
<212> PRT
<213> 智人
<400> 16
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Gly
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg
<210> 17
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 17
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 18
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 18
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 19
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 19
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 20
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 20
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 21
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 21
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Lys Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 22
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 22
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 23
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 23
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Arg Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 24
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 24
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 25
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 25
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Arg Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 26
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 26
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 27
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 27
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Leu Glu Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 28
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 28
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Lys Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 29
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 29
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Leu Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 30
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 30
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Glu Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 31
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 31
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Gly
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 32
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 32
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Phe
65 70 75 80
Ser Leu Arg Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 33
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 33
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile
65 70 75 80
Ser Leu Lys Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 34
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 34
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Leu Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 35
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 35
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe
65 70 75 80
Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Leu Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 36
<211> 117
<212> PRT
<213> 智人
<400> 36
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 37
<211> 117
<212> PRT
<213> 智人
<400> 37
Gln Pro Val Leu Thr Gln Pro Pro Ser Ser Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser Asp Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Ala Ser Ala Asn Thr Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Ile Trp Pro Ser Asn Ala Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 38
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 38
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 39
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 39
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Ala Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 40
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 40
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Arg Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 41
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 41
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Ala
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 42
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 42
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Arg Tyr Arg Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 43
<211> 115
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 43
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Ser Thr Asn Ser Gly Ile Leu Leu
65 70 75 80
Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys Met Thr
85 90 95
Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln Leu Thr
100 105 110
Val Leu Gly
115
<210> 44
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 44
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Gly Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 45
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 45
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ala Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 46
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 46
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Arg Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 47
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 47
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Arg Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 48
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 48
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Thr Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 49
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 49
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Arg Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 50
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 50
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Pro Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 51
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 51
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Ile Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 52
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 52
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 53
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 53
Gln Pro Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 54
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 54
Gln Ala Val Leu Thr Gln Pro Pro Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 55
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 55
Gln Ala Val Leu Thr Gln Pro Ala Ser Ser Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 56
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 56
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 57
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 57
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 58
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 58
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser Asp Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 59
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 59
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Ala Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 60
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 60
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Ala Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 61
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 61
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Thr Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 62
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 62
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Ile Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 63
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 63
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Pro Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 64
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 64
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Ala Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 65
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 65
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 66
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 66
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 67
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 67
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 68
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 68
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 69
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 69
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gly Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 70
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 70
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr His Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 71
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 71
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Lys Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 72
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 72
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Pro Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 73
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 73
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Glu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 74
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 74
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Gly Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 75
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 75
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Asn Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 76
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 76
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Pro Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 77
<211> 117
<212> PRT
<213> 智人
<400> 77
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Ser Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 78
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 78
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Glu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 79
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 79
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Pro Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 80
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 80
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Glu Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 81
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 81
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Gln Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 82
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 82
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Pro Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 83
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 83
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Asn Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 84
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 84
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Thr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 85
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 85
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Asp Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 86
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 86
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 87
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 87
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr His Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 88
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 88
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 89
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 89
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser Asn Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 90
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 90
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser Pro Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 91
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 91
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Asp Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 92
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 92
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 93
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 93
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 94
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 94
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 95
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 95
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 96
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 96
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 97
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 97
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 98
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 98
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 99
<211> 117
<212> PRT
<213> 合成物
<400> 99
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 100
<211> 117
<212> PRT
<213> 合成物
<400> 100
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 101
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 101
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 102
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 102
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 103
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 103
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 104
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 104
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 105
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 105
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 106
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 106
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 107
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 107
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 108
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 108
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 109
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 109
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 110
<211> 122
<212> PRT
<213> 智人
<400> 110
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Asn Gly Gly Val Thr Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Asp Ile Arg Met Ser Gly Trp Leu Ala Pro Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 111
<211> 120
<212> PRT
<213> 智人
<400> 111
Gln Val Gln Leu Val Glu Ser Gly Gly Gly Val Val Gln Gly Gly Gly
1 5 10 15
Ser Leu Arg Leu Ser Cys Ala Ala Ser Gly Phe Thr Val Arg Ser Asn
20 25 30
Tyr Met Ser Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Val
35 40 45
Ser Ala Ile Ser Gly Ser Gly Asp Ser Thr Tyr Tyr Ala Asp Ser Val
50 55 60
Lys Gly Arg Phe Thr Ile Ser Arg Asp Asn Ser Lys Asn Thr Leu Tyr
65 70 75 80
Leu Gln Met Asn Ser Leu Arg Ala Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Lys Val Ala Val Thr Thr Gly Trp Tyr Phe Asp Leu Trp Gly Arg
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 112
<211> 117
<212> PRT
<213> 智人
<400> 112
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Asp Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Thr Ser Ala Asn Thr Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr Tyr Cys
85 90 95
Met Ile Trp Ala Ser Asn Gly Ser Gly Val Leu Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 113
<211> 117
<212> PRT
<213> 智人
<400> 113
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr
20 25 30
His Asn Ile Tyr Trp Tyr Gln Glu Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser Ser Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Thr Gly Ile
65 70 75 80
Leu Val Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Glu Tyr Tyr Cys
85 90 95
Met Thr Trp Ser Ser Asn Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 114
<211> 120
<212> PRT
<213> 褐家鼠（Rattus norvegicus）
<400> 114
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Val Gly Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Ser Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Lys Lys Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Ile Gln Leu Ser Ser Leu Ala Ser Glu Asp Thr Ala Thr Tyr Phe Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 115
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 115
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 116
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 116
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 117
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 117
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 118
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 118
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 119
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 119
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 120
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 120
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 121
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 121
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 122
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 122
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 123
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 123
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Ile Thr Arg Asp Arg Ser Met Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 124
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 124
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Ile Thr Ala Asp Arg Ser Met Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr Trp Gly Gln
100 105 110
Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 125
<211> 108
<212> PRT
<213> 褐家鼠
<400> 125
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Thr Val Thr Ile Glu Cys Arg Ala Ser Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Asn Ser Pro Gln Leu Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Ala
50 55 60
Ser Gly Ser Gly Thr Gln Phe Ser Leu Lys Ile Asn Ser Leu Arg Ser
65 70 75 80
Glu Asp Val Ala Ser Tyr Phe Cys Gln Gln Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg
100 105
<210> 126
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 126
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Asp Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 127
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 127
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Gln Gln Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 128
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 128
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp 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 Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 129
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 129
Ala Ile Gln Leu 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 Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp 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 Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 130
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 130
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 Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp 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 Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 131
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 131
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Arg Ala Ser Glu Asp Ile Tyr Ser Asn
20 25 30
Leu Ala Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Asp Ala Asn Ser Leu Ala Asp Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Gln Gln Tyr Asn Asn Tyr Pro Tyr
85 90 95
Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
100 105
<210> 132
<211> 123
<212> PRT
<213> 褐家鼠
<400> 132
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Val Gly Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Lys Gln Ser Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Lys Lys Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr
65 70 75 80
Ile Gln Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 133
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 133
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 134
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 134
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Ile Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 135
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 135
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 136
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 136
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 137
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 137
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Leu
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 138
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 138
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 139
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 139
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 140
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 140
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 141
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 141
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Ile Thr Arg Asp Arg Ser Met Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 142
<211> 123
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 142
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Ile Met His Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Ile Thr Ala Asp Arg Ser Met Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
100 105 110
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 143
<211> 113
<212> PRT
<213> 褐家鼠
<400> 143
Asp Ile Val Met Thr Gln Gly Ala Leu Pro Asn Pro Val Pro Ser Gly
1 5 10 15
Glu Ser Ala Ser Ile Thr Cys Gln Ser Ser Glu Ser Leu Leu His Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Tyr Leu Gln Arg Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Trp Met Ser Thr Arg Ala Ala Gly Val Ser
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile
65 70 75 80
Ser Gly Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Phe
85 90 95
Leu Glu Tyr Pro Pro Thr Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 144
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 144
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Ser Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Gln Ser Ser Glu Ser Leu Leu His Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Leu Gln Gln Arg Pro Gly Gln Pro
35 40 45
Pro Arg Leu Leu Ile Tyr Trp Met Ser Thr Arg Ala Ala Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ala Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Phe
85 90 95
Leu Glu Tyr Pro Pro Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 145
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 145
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys Gln Ser Ser Glu Ser Leu Leu His Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Tyr Leu Gln Lys Pro Gly Gln Ser
35 40 45
Pro Gln Leu Leu Ile Tyr Trp Met Ser Thr Arg Ala Ala Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Phe
85 90 95
Leu Glu Tyr Pro Pro Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 146
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 146
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Gln Ser Ser Glu Ser Leu Leu His Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Tyr Leu Gln Lys Pro Gly Gln Pro
35 40 45
Pro Gln Leu Leu Ile Tyr Trp Met Ser Thr Arg Ala Ala Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Phe
85 90 95
Leu Glu Tyr Pro Pro Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 147
<211> 113
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 147
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys Gln Ser Ser Glu Ser Leu Leu His Ser
20 25 30
Asn Gly Lys Thr Tyr Leu Asn Trp Phe Gln Gln Arg Pro Gly Gln Ser
35 40 45
Pro Arg Arg Leu Ile Tyr Trp Met Ser Thr Arg Ala Ala Gly Val Pro
50 55 60
Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile
65 70 75 80
Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Gln Gln Phe
85 90 95
Leu Glu Tyr Pro Pro Thr Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys
100 105 110
Arg
<210> 148
<211> 120
<212> PRT
<213> 褐家鼠
<400> 148
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Val Gly Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Lys Gln Ser Pro Gly Gln Gly Leu Glu Trp Ile
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Lys Lys Lys Ala Thr Leu Thr Ala Asp Ser Ser Ser Ser Thr Ala Tyr
65 70 75 80
Ile Tyr Leu Ser Gly Leu Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Ser Leu Val Thr Val Ser Ser
115 120
<210> 149
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 149
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 150
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 150
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 151
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 151
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 152
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 152
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 153
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 153
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Ile Thr Arg Asp Arg Ser Met Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 154
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 154
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Asp Arg Val Thr Ile Thr Ala Asp Arg Ser Met Ser Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 155
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 155
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 156
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 156
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 157
<211> 108
<212> PRT
<213> 褐家鼠
<400> 157
Asp Ile Val Met Thr Gln Ser Pro Thr Ser Ile Ser Ile Ser Val Gly
1 5 10 15
Glu Arg Val Thr Met Asn Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Thr Gly Gln Ser Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Asp Arg Phe Thr Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Asn Met Gln Ala
65 70 75 80
Glu Asp Leu Ala Val Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg
100 105
<210> 158
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 158
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 159
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 159
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 160
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 160
Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Phe Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 161
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 161
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 162
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 162
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Arg Asp Phe Thr Leu Thr Ile Ser Ser Leu Glu Pro
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 163
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 163
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Ile Pro Ala Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Glu Phe Thr Leu Thr Ile Ser Ser Leu Gln Ser
65 70 75 80
Glu Asp Phe Ala Val Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 164
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 164
Glu Ile Val Leu Thr Gln Ser Pro Asp Phe Gln Ser Val Thr Pro Lys
1 5 10 15
Glu Lys Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Asp Gln Ser Pro Lys Leu Leu Ile
35 40 45
Lys Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Leu Thr Ile Asn Ser Leu Glu Ala
65 70 75 80
Glu Asp Ala Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 165
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 165
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Glu Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 166
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 166
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Gly Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 167
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 167
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln His Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 168
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 168
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Gln Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 169
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 169
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ser Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 170
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 170
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Val Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 171
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 171
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Glu Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 172
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 172
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Pro Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 173
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 173
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Gln Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 174
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 174
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Ser Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 175
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 175
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Glu Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 176
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 176
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Gly Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 177
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 177
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Pro Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 178
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 178
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Thr Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 179
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 179
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 180
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 180
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Thr Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 181
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 181
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 Glu Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 182
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 182
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 Gly Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 183
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 183
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 Pro Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 184
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 184
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 Gln Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 185
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 185
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Asp Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 186
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 186
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Asp
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 187
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 187
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Glu Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 188
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 188
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 189
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 189
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Glu Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 190
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 190
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys His Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 191
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 191
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Lys Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 192
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 192
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Pro Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 193
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 193
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 194
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 194
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ser Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 195
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 195
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Val Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 196
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 196
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Asp Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 197
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 197
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Lys Tyr Gln Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 198
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 198
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys Lys Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Gln Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Met Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 199
<211> 30
<212> PRT
<213> 智人
<400> 199
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser
20 25 30
<210> 200
<211> 7
<212> PRT
<213> 智人
<400> 200
Ser Ser Ser Tyr Tyr Trp Ser
1 5
<210> 201
<211> 14
<212> PRT
<213> 智人
<400> 201
Trp Ile Arg Gln His Pro Gly Lys Gly Leu Glu Trp Ile Gly
1 5 10
<210> 202
<211> 16
<212> PRT
<213> 智人
<400> 202
Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser Leu Lys Ser
1 5 10 15
<210> 203
<211> 32
<212> PRT
<213> 智人
<400> 203
Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile Ser Leu Arg
1 5 10 15
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 204
<211> 11
<212> PRT
<213> 智人
<400> 204
Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val
1 5 10
<210> 205
<211> 11
<212> PRT
<213> 智人
<400> 205
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 206
<211> 30
<212> PRT
<213> 智人
<400> 206
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser
20 25 30
<210> 207
<211> 7
<212> PRT
<213> 智人
<400> 207
Ser Gly Ser Tyr Tyr Trp Ser
1 5
<210> 208
<211> 14
<212> PRT
<213> 智人
<400> 208
Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly
1 5 10
<210> 209
<211> 32
<212> PRT
<213> 智人
<400> 209
Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys
1 5 10 15
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 210
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 210
Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Ile Ser Leu Arg
1 5 10 15
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 211
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 211
Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly
1 5 10
<210> 212
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 212
Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile Ser Leu Arg
1 5 10 15
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 213
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 213
Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys
1 5 10 15
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 214
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 214
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Lys Val Ser Gly Gly Ser Ile Ser
20 25 30
<210> 215
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 215
Gln Val Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser
20 25 30
<210> 216
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 216
Arg Val Thr Ile Ser Arg Asp Thr Leu Lys Asn Gln Ile Ser Leu Arg
1 5 10 15
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 217
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 217
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Val Ser
20 25 30
<210> 218
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 218
Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile Ser Leu Arg
1 5 10 15
Leu Thr Ser Val Arg Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 219
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 219
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Lys Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser
20 25 30
<210> 220
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 220
Val Gly Gly Ala Gly Gly Trp Pro Leu Glu Val
1 5 10
<210> 221
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 221
Arg Val Thr Ile Ser Val Asp Lys Leu Lys Asn Gln Ile Ser Leu Arg
1 5 10 15
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 222
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 222
Val Gly Gly Ala Gly Gly Trp Pro Leu Asp Val
1 5 10
<210> 223
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的.
<400> 223
Val Gly Gly Ala Gly Gly Trp Pro Met Glu Val
1 5 10
<210> 224
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 224
Ser Gly Ser Tyr Tyr Trp Ser
1 5
<210> 225
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 225
Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Phe Ser Leu Arg
1 5 10 15
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 226
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 226
Arg Val Thr Ile Ser Val Asp Thr Leu Lys Asn Gln Ile Ser Leu Lys
1 5 10 15
Leu Thr Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 227
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 227
Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys
1 5 10 15
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 228
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 228
Val Gly Gly Ala Gly Gly Trp Pro Leu Asp Val
1 5 10
<210> 229
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 229
Trp Ile Arg Gln Pro Pro Gly Lys Gly Leu Glu Trp Ile Gly
1 5 10
<210> 230
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 230
Arg Val Thr Ile Ser Val Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys
1 5 10 15
Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 231
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 231
Val Gly Gly Ala Gly Gly Trp Pro Met Asp Val
1 5 10
<210> 232
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 232
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys
20
<210> 233
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 233
Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr Tyr Asn Ile Tyr
1 5 10
<210> 234
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 234
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Leu Tyr
1 5 10 15
<210> 235
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 235
Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 236
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 236
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr
20 25 30
Tyr Cys
<210> 237
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 237
Met Thr Trp Ser Ser Asn Gly Ser Gly Val
1 5 10
<210> 238
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 238
Phe Gly Gly Gly Thr Gln Leu Thr Val Leu Gly
1 5 10
<210> 239
<211> 22
<212> PRT
<213> 智人
<400> 239
Gln Pro Val Leu Thr Gln Pro Pro Ser Ser Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys
20
<210> 240
<211> 14
<212> PRT
<213> 智人
<400> 240
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 241
<211> 11
<212> PRT
<213> 智人
<400> 241
Tyr Tyr Ser Asp Ser Asp Lys Gly Gln Gly Ser
1 5 10
<210> 242
<211> 34
<212> PRT
<213> 智人
<400> 242
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Ala Ser Ala Asn Thr
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr
20 25 30
Tyr Cys
<210> 243
<211> 8
<212> PRT
<213> 智人
<400> 243
Met Ile Trp Pro Ser Asn Ala Ser
1 5
<210> 244
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 244
Met Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 245
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 245
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Ala Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr
20 25 30
Tyr Cys
<210> 246
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 246
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Leu Arg
1 5 10 15
<210> 247
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 247
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Ala
1 5 10 15
Ser Ala Arg Leu Thr Cys
20
<210> 248
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 248
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Leu Arg
1 5 10 15
<210> 249
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 249
Tyr Arg Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 250
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的.
<400> 250
Thr Leu Pro Ser Gly Ile Asn Val Arg Tyr Tyr Asn Ile Tyr
1 5 10
<210> 251
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 251
Met Thr Trp Ser Ser Asn Gly Ala Gly Val
1 5 10
<210> 252
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 252
Thr Leu Pro Ser Asp Ile Asn Val Arg Tyr Tyr Arg Ile Tyr
1 5 10
<210> 253
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 253
Tyr Arg Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 254
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 254
Met Thr Trp Ser Ser Thr Gly Ser Gly Val
1 5 10
<210> 255
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 255
Thr Leu Arg Ser Asp Ile Asn Val Arg Tyr Tyr Asn Ile Tyr
1 5 10
<210> 256
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 256
Met Thr Trp Ser Ser Asn Pro Ser Gly Val
1 5 10
<210> 257
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 257
Ile Thr Trp Ser Ser Asn Gly Ser Gly Val
1 5 10
<210> 258
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 258
Leu Thr Trp Ser Ser Asn Gly Ser Gly Val
1 5 10
<210> 259
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 259
Gln Pro Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys
20
<210> 260
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 260
Gln Ala Val Leu Thr Gln Pro Pro Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys
20
<210> 261
<211> 22
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 261
Gln Ala Val Leu Thr Gln Pro Ala Ser Ser Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys
20
<210> 262
<211> 14
<212> PRT
<213> 合成物
<400> 262
Thr Leu Pro Ser Asp Ile Asn Val Gly Tyr Tyr Asn Ile Tyr
1 5 10
<210> 263
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 263
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 264
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 264
Tyr Tyr Ser Asp Ser Asp Lys Gly Gln Gly Ser
1 5 10
<210> 265
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 265
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Ala Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr
20 25 30
Tyr Cys
<210> 266
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 266
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Ala Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr
20 25 30
Tyr Cys
<210> 267
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 267
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Thr
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Glu Ala Asp Tyr
20 25 30
Tyr Cys
<210> 268
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 268
Met Ile Trp Ser Ser Asn Gly Ser Gly Val
1 5 10
<210> 269
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 269
Met Thr Trp Pro Ser Asn Gly Ser Gly Val
1 5 10
<210> 270
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 270
Met Thr Trp Ser Ser Asn Ala Ser Gly Val
1 5 10
<210> 271
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 271
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 272
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 272
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 273
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 273
Leu Thr Trp Ser Ser Asn Gly Ser Gly Val
1 5 10
<210> 274
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 274
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 275
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 275
Met Thr Trp Ser Ser Asn Gly Ser Gly Val
1 5 10
<210> 276
<211> 34
<212> PRT
<213> 合成物
<400> 276
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 277
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 277
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gly Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 278
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 278
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr His Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 279
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 279
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Lys Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 280
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 280
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Pro Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 281
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 281
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Glu Leu Tyr
1 5 10 15
<210> 282
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 282
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 283
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 283
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Gly Leu Tyr
1 5 10 15
<210> 284
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 284
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 285
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 285
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Asn Leu Tyr
1 5 10 15
<210> 286
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 286
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 287
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 287
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Pro Leu Tyr
1 5 10 15
<210> 288
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 288
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 289
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 289
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Ser Leu Tyr
1 5 10 15
<210> 290
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 290
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 291
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 291
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Glu Tyr
1 5 10 15
<210> 292
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 292
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 293
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 293
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Pro Tyr
1 5 10 15
<210> 294
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 294
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 295
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 295
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Leu Glu
1 5 10 15
<210> 296
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 296
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 297
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 297
Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr Leu Leu Gln
1 5 10 15
<210> 298
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 298
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 299
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 299
Pro Tyr Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 300
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 300
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 301
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 301
Asn Tyr Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 302
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 302
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 303
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 303
Thr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 304
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 304
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 305
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 305
Tyr Asp Ser Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 306
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的.
<400> 306
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 307
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 307
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 308
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 308
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 309
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 309
Tyr Tyr His Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 310
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 310
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 311
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 311
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 312
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 312
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 313
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 313
Tyr Tyr Ser Asp Ser Asn Lys Gly Gln Gly Ser
1 5 10
<210> 314
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 314
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 315
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 315
Tyr Tyr Ser Asp Ser Pro Lys Gly Gln Gly Ser
1 5 10
<210> 316
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 316
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 317
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 317
Tyr Tyr Ser Asp Ser His Asp Gly Gln Gly Ser
1 5 10
<210> 318
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 318
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 319
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 319
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 320
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 320
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 321
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 321
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 322
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 322
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 323
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 323
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 324
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 324
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 325
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 325
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 326
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 326
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 327
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 327
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 328
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 328
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 329
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 329
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 330
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 330
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 331
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 331
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 332
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 332
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 333
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 333
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 334
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 334
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 335
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 335
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 336
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 336
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 337
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 337
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 338
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 338
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 339
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 339
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 340
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 340
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 341
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 341
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 342
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 342
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 343
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 343
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 344
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 344
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 345
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 345
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 346
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 346
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 347
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 347
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 348
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 348
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 349
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 349
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 350
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 350
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 351
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 351
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 352
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 352
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 353
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的.
<400> 353
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 354
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 354
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 355
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 355
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Asn Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 356
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 356
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 357
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 357
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 358
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的.
<400> 358
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 359
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 359
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 360
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 360
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 361
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 361
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 362
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 362
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 363
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 363
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 364
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 364
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 365
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 365
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 366
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 366
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 367
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 367
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 368
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 368
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 369
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 369
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 370
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 370
Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 371
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 371
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 372
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 372
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 373
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 373
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 374
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 374
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 375
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 375
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 376
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 376
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 377
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 377
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 378
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 378
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 379
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 379
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 380
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 380
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val
1 5 10
<210> 381
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 381
Thr Leu Pro Ser Asp Ile Asn Val Gly Ser Tyr Asn Ile Tyr
1 5 10
<210> 382
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 382
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 383
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 383
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 384
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 384
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 385
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 385
Thr Leu Pro Ser Asp Ile Asn Val Arg Ser Tyr Asn Ile Tyr
1 5 10
<210> 386
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 386
Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser
1 5 10
<210> 387
<211> 34
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 387
Gly Val Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Gln Ser
1 5 10 15
Gly Ile Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr
20 25 30
Tyr Cys
<210> 388
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 388
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val
1 5 10
<210> 389
<211> 30
<212> PRT
<213> 褐家鼠
<400> 389
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Val Gly Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 390
<211> 5
<212> PRT
<213> 褐家鼠
<400> 390
Asp Tyr Ile Met His
1 5
<210> 391
<211> 14
<212> PRT
<213> 褐家鼠
<400> 391
Trp Val Lys Gln Ser Pro Gly Gln Gly Leu Glu Trp Ile Gly
1 5 10
<210> 392
<211> 17
<212> PRT
<213> 褐家鼠
<400> 392
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Glu Lys Phe Lys
1 5 10 15
Lys
<210> 393
<211> 32
<212> PRT
<213> 褐家鼠
<400> 393
Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr Ile Gln
1 5 10 15
Leu Ser Ser Leu Ala Ser Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
20 25 30
<210> 394
<211> 11
<212> PRT
<213> 褐家鼠
<400> 394
Ser Ala His Thr Thr Gly Phe Gly Phe Ala Tyr
1 5 10
<210> 395
<211> 11
<212> PRT
<213> 褐家鼠
<400> 395
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
<210> 396
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 396
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 397
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 397
Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 398
<211> 17
<212> PRT
<213> 合成物
<400> 398
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 399
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 399
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 400
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 400
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 401
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 401
Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 402
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 402
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 403
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 403
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 404
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 404
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 405
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 405
Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10
<210> 406
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 406
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Leu Gln
1 5 10 15
Gly
<210> 407
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 407
Arg Val Thr Met Thr Thr Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 408
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 408
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 409
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 409
Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10
<210> 410
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 410
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Leu Gln
1 5 10 15
Gly
<210> 411
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 411
Arg Val Thr Met Thr Ala Asp Thr Ser Thr Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Arg Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 412
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 412
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 413
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 413
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 414
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 414
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 415
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 415
Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 416
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 416
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 417
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 417
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 418
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 418
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 419
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 419
Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 420
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 420
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 421
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 421
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 422
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 422
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 423
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 423
Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 424
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 424
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 425
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 425
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 426
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 426
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 427
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 427
Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 428
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 428
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 429
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 429
Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met Gly
1 5 10
<210> 430
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 430
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Asp
<210> 431
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 431
Arg Val Thr Ile Thr Arg Asp Arg Ser Met Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Arg
20 25 30
<210> 432
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 432
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 433
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 433
Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met Gly
1 5 10
<210> 434
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 434
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Asp
<210> 435
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 435
Arg Val Thr Ile Thr Ala Asp Arg Ser Met Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Arg
20 25 30
<210> 436
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 436
Asp Ile Gln Met Thr Gln Ser Pro Ala Ser Leu Ser Ala Ser Leu Gly
1 5 10 15
Glu Thr Val Thr Ile Glu Cys
20
<210> 437
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 437
Arg Ala Ser Glu Asp Ile Tyr Ser Asn Leu Ala
1 5 10
<210> 438
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 438
Trp Tyr Gln Gln Lys Pro Gly Asn Ser Pro Gln Leu Leu Ile Tyr
1 5 10 15
<210> 439
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 439
Asp Ala Asn Ser Leu Ala Asp
1 5
<210> 440
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 440
Gly Val Pro Ser Arg Phe Ser Ala Ser Gly Ser Gly Thr Gln Phe Ser
1 5 10 15
Leu Lys Ile Asn Ser Leu Arg Ser Glu Asp Val Ala Ser Tyr Phe Cys
20 25 30
<210> 441
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 441
Gln Gln Tyr Asn Asn Tyr Pro Tyr Thr
1 5
<210> 442
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 442
Phe Gly Ala Gly Thr Lys Leu Glu Leu Lys Arg
1 5 10
<210> 443
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 443
Asp Ile Gln Met Thr Gln Ser Pro Ser Thr Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 444
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 444
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 445
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 445
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Asp Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 446
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 446
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 447
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 447
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 448
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 448
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 449
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 449
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 450
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 450
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 451
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 451
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 452
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 452
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 453
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 453
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 454
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 454
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 455
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 455
Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 456
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 456
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 457
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 457
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 458
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 458
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 459
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 459
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Glu Asp Arg Thr Ile Thr Cys
20
<210> 460
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 460
Trp Tyr Gln Gln Lys Pro Glu Lys Ala Pro Lys Ser Leu Ile Tyr
1 5 10 15
<210> 461
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 461
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 462
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 462
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 463
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 463
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys
20
<210> 464
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 464
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
1 5 10 15
<210> 465
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 465
Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys
20 25 30
<210> 466
<211> 30
<212> PRT
<213> 褐家鼠
<400> 466
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Val Gly Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Ile Phe Thr
20 25 30
<210> 467
<211> 17
<212> PRT
<213> 褐家鼠
<400> 467
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe Lys
1 5 10 15
Lys
<210> 468
<211> 32
<212> PRT
<213> 褐家鼠
<400> 468
Lys Ala Thr Leu Thr Ala Asp Thr Ser Ser Ser Thr Ala Tyr Ile Gln
1 5 10 15
Leu Ser Ser Leu Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
20 25 30
<210> 469
<211> 14
<212> PRT
<213> 褐家鼠
<400> 469
Val Ala Ile Ile Thr Thr Val Ala Ser Gly Gly Phe Ala Tyr
1 5 10
<210> 470
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 470
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 471
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 471
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 472
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 472
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Ile Phe Thr
20 25 30
<210> 473
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 473
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 474
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 474
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 475
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 475
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 476
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 476
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 477
<211> 17
<212> PRT
<213> 合成物
<400> 477
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Leu Gln
1 5 10 15
Gly
<210> 478
<211> 30
<212> PRT
<213> 合成物
<400> 478
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 479
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 479
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Leu Gln
1 5 10 15
Gly
<210> 480
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 480
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 481
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 481
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 482
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 482
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 483
<211> 17
<212> PRT
<213> 合成物
<400> 483
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 484
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 484
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 485
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 485
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 486
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 486
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 487
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 487
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Asp
<210> 488
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 488
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 489
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 489
Trp Ile Asp Pro Glu Tyr Gly Ser Thr Asp Tyr Ala Gln Lys Phe Gln
1 5 10 15
Asp
<210> 490
<211> 23
<212> PRT
<213> 褐家鼠
<400> 490
Asp Ile Val Met Thr Gln Gly Ala Leu Pro Asn Pro Val Pro Ser Gly
1 5 10 15
Glu Ser Ala Ser Ile Thr Cys
20
<210> 491
<211> 16
<212> PRT
<213> 褐家鼠
<400> 491
Gln Ser Ser Glu Ser Leu Leu His Ser Asn Gly Lys Thr Tyr Leu Asn
1 5 10 15
<210> 492
<211> 15
<212> PRT
<213> 褐家鼠
<400> 492
Trp Tyr Leu Gln Arg Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr
1 5 10 15
<210> 493
<211> 7
<212> PRT
<213> 褐家鼠
<400> 493
Trp Met Ser Thr Arg Ala Ala
1 5
<210> 494
<211> 32
<212> PRT
<213> 褐家鼠
<400> 494
Gly Val Ser Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Gly Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
20 25 30
<210> 495
<211> 9
<212> PRT
<213> 褐家鼠
<400> 495
Gln Gln Phe Leu Glu Tyr Pro Pro Thr
1 5
<210> 496
<211> 11
<212> PRT
<213> 褐家鼠
<400> 496
Phe Gly Ser Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 497
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 497
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Ser Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys
20
<210> 498
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 498
Trp Leu Gln Gln Arg Pro Gly Gln Pro Pro Arg Leu Leu Ile Tyr
1 5 10 15
<210> 499
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 499
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ala Gly Thr Asp Phe Thr
1 5 10 15
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
20 25 30
<210> 500
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 500
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 501
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 501
Asp Ile Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Pro Gly
1 5 10 15
Glu Pro Ala Ser Ile Ser Cys
20
<210> 502
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 502
Trp Tyr Leu Gln Lys Pro Gly Gln Ser Pro Gln Leu Leu Ile Tyr
1 5 10 15
<210> 503
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 503
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
20 25 30
<210> 504
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 504
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 505
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 505
Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys
20
<210> 506
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 506
Trp Tyr Leu Gln Lys Pro Gly Gln Pro Pro Gln Leu Leu Ile Tyr
1 5 10 15
<210> 507
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 507
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
20 25 30
<210> 508
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 508
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 509
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 509
Asp Val Val Met Thr Gln Ser Pro Leu Ser Leu Pro Val Thr Leu Gly
1 5 10 15
Gln Pro Ala Ser Ile Ser Cys
20
<210> 510
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 510
Trp Phe Gln Gln Arg Pro Gly Gln Ser Pro Arg Arg Leu Ile Tyr
1 5 10 15
<210> 511
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 511
Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys
20 25 30
<210> 512
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 512
Phe Gly Gln Gly Thr Lys Leu Glu Ile Lys Arg
1 5 10
<210> 513
<211> 30
<212> PRT
<213> 褐家鼠
<400> 513
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 514
<211> 5
<212> PRT
<213> 褐家鼠
<400> 514
Asp Ser Val Met Asn
1 5
<210> 515
<211> 14
<212> PRT
<213> 褐家鼠
<400> 515
Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 516
<211> 17
<212> PRT
<213> 褐家鼠
<400> 516
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 517
<211> 32
<212> PRT
<213> 褐家鼠
<400> 517
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 518
<211> 11
<212> PRT
<213> 褐家鼠
<400> 518
Thr Lys Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr
1 5 10
<210> 519
<211> 11
<212> PRT
<213> 褐家鼠
<400> 519
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 520
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 520
Trp Val Gln Gln Glu Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 521
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 521
Trp Val Gln Gln Gly Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 522
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 522
Trp Val Gln Gln His Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 523
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 523
Trp Val Gln Gln Gln Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 524
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 524
Trp Val Gln Gln Ser Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 525
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 525
Trp Val Gln Gln Val Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 526
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 526
Asp Ser Val Met Glu
1 5
<210> 527
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 527
Asp Ser Val Met Pro
1 5
<210> 528
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 528
Asp Ser Val Met Gln
1 5
<210> 529
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 529
Asp Ser Val Met Ser
1 5
<210> 530
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 530
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Glu
20 25 30
<210> 531
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 531
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Gly
20 25 30
<210> 532
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 532
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Pro
20 25 30
<210> 533
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 533
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 534
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 534
Thr Gly Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr
1 5 10
<210> 535
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 535
Thr Thr Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr
1 5 10
<210> 536
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 536
Thr Lys Tyr Gln Ser Gly Tyr Gly Phe Pro Tyr
1 5 10
<210> 537
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 537
Glu Val Gln Leu Gln Gln Ser Gly Pro Glu Val Gly Arg Pro Gly Ser
1 5 10 15
Ser Val Lys Ile Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 538
<211> 14
<212> PRT
<213> 合成物
<400> 538
Trp Val Lys Gln Ser Pro Gly Gln Gly Leu Glu Trp Ile Gly
1 5 10
<210> 539
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 539
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe Lys
1 5 10 15
Lys
<210> 540
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 540
Lys Ala Thr Leu Thr Ala Asp Ser Ser Ser Ser Thr Ala Tyr Ile Tyr
1 5 10 15
Leu Ser Gly Leu Thr Ser Glu Asp Thr Ala Thr Tyr Phe Cys Ala Arg
20 25 30
<210> 541
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 541
Trp Gly Gln Gly Ser Leu Val Thr Val Ser Ser
1 5 10
<210> 542
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 542
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 543
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 543
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 544
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 544
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 545
<211> 33
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 545
Gly Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr Met
1 5 10 15
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala
20 25 30
Thr
<210> 546
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 546
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 547
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 547
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 548
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 548
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 549
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 549
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 550
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 550
Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 551
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 551
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 552
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 552
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 553
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 553
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 554
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 554
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 555
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 555
Arg Val Thr Met Thr Glu Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 556
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 556
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 557
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 557
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr
20 25 30
<210> 558
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 558
Trp Val Arg Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 559
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 559
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 560
<211> 33
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 560
Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met
1 5 10 15
Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala
20 25 30
Arg
<210> 561
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 561
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 562
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 562
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 563
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 563
Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met Gly
1 5 10
<210> 564
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 564
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe Gln
1 5 10 15
Asp
<210> 565
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 565
Arg Val Thr Ile Thr Arg Asp Arg Ser Met Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Arg
20 25 30
<210> 566
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 566
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 567
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 567
Gln Met Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Thr Gly Ser
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 568
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 568
Trp Val Arg Gln Ala Pro Gly Gln Ala Leu Glu Trp Met Gly
1 5 10
<210> 569
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 569
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe Gln
1 5 10 15
Asp
<210> 570
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 570
Arg Val Thr Ile Thr Ala Asp Arg Ser Met Ser Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Met Tyr Tyr Cys Ala Arg
20 25 30
<210> 571
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 571
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 572
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 572
Glu Val Gln Leu Val Gln Ser Gly Pro Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 573
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 573
Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 574
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 574
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 575
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 575
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Thr
20 25 30
<210> 576
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 576
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 577
<211> 30
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 577
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 578
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 578
Trp Val Gln Gln Ala Pro Gly Lys Gly Leu Glu Trp Met Gly
1 5 10
<210> 579
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 579
Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe Gln
1 5 10 15
Gly
<210> 580
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 580
Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr Met Glu
1 5 10 15
Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 581
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 581
Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser
1 5 10
<210> 582
<211> 23
<212> PRT
<213> 褐家鼠
<400> 582
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
20
<210> 583
<211> 11
<212> PRT
<213> 褐家鼠
<400> 583
Lys Ala Ser Gln Asn Val Asp Ser Asp Val Asp
1 5 10
<210> 584
<211> 15
<212> PRT
<213> 褐家鼠
<400> 584
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 585
<211> 7
<212> PRT
<213> 褐家鼠
<400> 585
Lys Ala Ser Asn Arg Tyr Thr
1 5
<210> 586
<211> 32
<212> PRT
<213> 褐家鼠
<400> 586
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys
20 25 30
<210> 587
<211> 9
<212> PRT
<213> 褐家鼠
<400> 587
Met Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 588
<211> 11
<212> PRT
<213> 褐家鼠
<400> 588
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 589
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 589
Pro Ala Ser Gln Asn Val Asp Ser Asp Val Asp
1 5 10
<210> 590
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 590
Gln Ala Ser Gln Asn Val Asp Ser Asp Val Asp
1 5 10
<210> 591
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 591
Lys Ala Ser Asn Asp Tyr Thr
1 5
<210> 592
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 592
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Asp Tyr
1 5 10 15
<210> 593
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 593
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Glu
1 5 10 15
<210> 594
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 594
Ala Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 595
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 595
Glu Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 596
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 596
His Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 597
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 597
Lys Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 598
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 598
Pro Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 599
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 599
Gln Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 600
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 600
Ser Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 601
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 601
Val Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 602
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 602
Met Asp Ser Asn Thr His Pro Arg Thr
1 5
<210> 603
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 603
Met Gln Glu Asn Thr His Pro Arg Thr
1 5
<210> 604
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 604
Met Gln Ser Thr Thr His Pro Arg Thr
1 5
<210> 605
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 605
Lys Ala Ser Gln Arg Tyr Thr
1 5
<210> 606
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 606
Met Gln Ser Gln Thr His Pro Arg Thr
1 5
<210> 607
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 607
Asp Ile Val Met Thr Gln Ser Pro Thr Ser Ile Ser Ile Ser Val Gly
1 5 10 15
Glu Arg Val Thr Met Asn Cys
20
<210> 608
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 608
Lys Ala Ser Gln Asn Val Asp Ser Asp Val Asp
1 5 10
<210> 609
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 609
Trp Tyr Gln Gln Lys Thr Gly Gln Ser Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 610
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 610
Lys Ala Ser Asn Arg Tyr Thr
1 5
<210> 611
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 611
Gly Val Pro Asp Arg Phe Thr Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Phe Thr Ile Ser Asn Met Gln Ala Glu Asp Leu Ala Val Tyr Tyr Cys
20 25 30
<210> 612
<211> 9
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 612
Met Gln Ser Asn Thr His Pro Arg Thr
1 5
<210> 613
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 613
Phe Gly Gly Gly Thr Lys Leu Glu Leu Lys Arg
1 5 10
<210> 614
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 614
Asp Ile Gln Leu Thr Gln Ser Pro Ser Phe Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 615
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 615
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 616
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 616
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 617
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 617
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 618
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 618
Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Val Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 619
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 619
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 620
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 620
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 621
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 621
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 622
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 622
Ala Ile Gln Leu Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly
1 5 10 15
Asp Arg Val Thr Ile Thr Cys
20
<210> 623
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 623
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 624
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 624
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Pro Glu Asp Phe Ala Thr Tyr Tyr Cys
20 25 30
<210> 625
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 625
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 626
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 626
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
20
<210> 627
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 627
Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr
1 5 10 15
<210> 628
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 628
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys
20 25 30
<210> 629
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 629
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 630
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 630
Glu Ile Val Leu Thr Gln Ser Pro Ala Thr Leu Ser Leu Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys
20
<210> 631
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 631
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
1 5 10 15
<210> 632
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 632
Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Arg Asp Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Glu Pro Glu Asp Phe Ala Val Tyr Tyr Cys
20 25 30
<210> 633
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 633
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 634
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 634
Glu Ile Val Met Thr Gln Ser Pro Ala Thr Leu Ser Val Ser Pro Gly
1 5 10 15
Glu Arg Ala Thr Leu Ser Cys
20
<210> 635
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 635
Trp Tyr Gln Gln Lys Pro Gly Gln Ala Pro Arg Leu Leu Ile Tyr
1 5 10 15
<210> 636
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 636
Gly Ile Pro Ala Arg Phe Ser Gly Ser Gly Ser Gly Thr Glu Phe Thr
1 5 10 15
Leu Thr Ile Ser Ser Leu Gln Ser Glu Asp Phe Ala Val Tyr Tyr Cys
20 25 30
<210> 637
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 637
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 638
<211> 23
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 638
Glu Ile Val Leu Thr Gln Ser Pro Asp Phe Gln Ser Val Thr Pro Lys
1 5 10 15
Glu Lys Val Thr Ile Thr Cys
20
<210> 639
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 639
Trp Tyr Gln Gln Lys Pro Asp Gln Ser Pro Lys Leu Leu Ile Lys
1 5 10 15
<210> 640
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 640
Gly Val Pro Ser Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr
1 5 10 15
Leu Thr Ile Asn Ser Leu Glu Ala Glu Asp Ala Ala Thr Tyr Tyr Cys
20 25 30
<210> 641
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 641
Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
1 5 10
<210> 642
<211> 5
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 642
Gly Gly Gly Gly Ser
1 5
<210> 643
<211> 10
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 643
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10
<210> 644
<211> 15
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 644
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
1 5 10 15
<210> 645
<211> 20
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 645
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser
20
<210> 646
<211> 25
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 646
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
1 5 10 15
Gly Gly Gly Ser Gly Gly Gly Gly Ser
20 25
<210> 647
<211> 188
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 647
Met Ala Leu Thr Phe Ala Leu Leu Val Ala Leu Leu Val Leu Ser Cys
1 5 10 15
Lys Ser Ser Cys Ser Val Gly Cys Asp Leu Pro Gln Thr His Ser Leu
20 25 30
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
35 40 45
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
50 55 60
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
65 70 75 80
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Met Asp Ser Ser
85 90 95
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
100 105 110
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
115 120 125
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
130 135 140
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
145 150 155 160
Cys Ala Trp Glu Val Val Arg Asp Glu Ile Met Arg Ser Phe Ser Leu
165 170 175
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
180 185
<210> 648
<211> 165
<212> PRT
<213> 智人
<400> 648
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Met Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Ala Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu
165
<210> 649
<211> 165
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 649
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Met Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Asp Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu
165
<210> 650
<211> 188
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 650
Met Ala Leu Thr Phe Ala Leu Leu Val Ala Leu Leu Val Leu Ser Cys
1 5 10 15
Lys Ser Ser Cys Ser Val Gly Cys Asp Leu Pro Gln Thr His Ser Leu
20 25 30
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
35 40 45
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
50 55 60
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
65 70 75 80
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Met Asp Ser Ser
85 90 95
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
100 105 110
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
115 120 125
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
130 135 140
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
145 150 155 160
Cys Ala Trp Glu Val Val Arg Gly Glu Ile Met Arg Ser Phe Ser Leu
165 170 175
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
180 185
<210> 651
<211> 165
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 651
Cys Asp Leu Pro Gln Thr His Ser Leu Gly Ser Arg Arg Thr Leu Met
1 5 10 15
Leu Leu Ala Gln Met Arg Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp
20 25 30
Arg His Asp Phe Gly Phe Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln
35 40 45
Lys Ala Glu Thr Ile Pro Val Leu His Glu Met Ile Gln Gln Ile Phe
50 55 60
Asn Leu Phe Ser Thr Met Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu
65 70 75 80
Leu Asp Lys Phe Tyr Thr Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu
85 90 95
Ala Cys Val Ile Gln Gly Val Gly Val Thr Glu Thr Pro Leu Met Lys
100 105 110
Glu Asp Ser Ile Leu Ala Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu
115 120 125
Tyr Leu Lys Glu Lys Lys Tyr Ser Pro Cys Ala Trp Glu Val Val Arg
130 135 140
Gly Glu Ile Met Arg Ser Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser
145 150 155 160
Leu Arg Ser Lys Glu
165
<210> 652
<211> 492
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 652
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys Cys Asp Leu Pro Gln Thr His Ser Leu
325 330 335
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
340 345 350
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
355 360 365
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
370 375 380
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
385 390 395 400
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
405 410 415
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
420 425 430
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
435 440 445
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
450 455 460
Cys Ala Trp Glu Val Val Arg Asp Glu Ile Met Arg Ser Phe Ser Leu
465 470 475 480
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490
<210> 653
<211> 492
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 653
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Ser Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys Cys Asp Leu Pro Gln Thr His Ser Leu
325 330 335
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
340 345 350
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
355 360 365
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
370 375 380
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
385 390 395 400
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
405 410 415
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
420 425 430
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
435 440 445
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
450 455 460
Cys Ala Trp Glu Val Val Arg Gly Glu Ile Met Arg Ser Phe Ser Leu
465 470 475 480
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490
<210> 654
<211> 492
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 654
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys Cys Asp Leu Pro Gln Thr His Ser Leu
325 330 335
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
340 345 350
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
355 360 365
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
370 375 380
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
385 390 395 400
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
405 410 415
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
420 425 430
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
435 440 445
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
450 455 460
Cys Ala Trp Glu Val Val Arg Gly Glu Ile Met Arg Ser Phe Ser Leu
465 470 475 480
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490
<210> 655
<211> 495
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 655
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Met Ile Ser Arg Thr Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Cys Asp Leu Pro Gln Thr
325 330 335
His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg
340 345 350
Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe
355 360 365
Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro
370 375 380
Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys
385 390 395 400
Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr
405 410 415
Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly
420 425 430
Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala
435 440 445
Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys
450 455 460
Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Gly Glu Ile Met Arg Ser
465 470 475 480
Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490 495
<210> 656
<211> 495
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 656
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Cys Asp Leu Pro Gln Thr
325 330 335
His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg
340 345 350
Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe
355 360 365
Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro
370 375 380
Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys
385 390 395 400
Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr
405 410 415
Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly
420 425 430
Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala
435 440 445
Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys
450 455 460
Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Asp Glu Ile Met Arg Ser
465 470 475 480
Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490 495
<210> 657
<211> 495
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 657
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Ser Ser Lys
1 5 10 15
Ser Thr Ser Gly Gly Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Gln Thr
65 70 75 80
Tyr Ile Cys Asn Val Asn His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Lys Val Glu Pro Lys Ser Cys Asp Lys Thr His Thr Cys Pro Pro Cys
100 105 110
Pro Ala Pro Glu Leu Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro
115 120 125
Lys Pro Lys Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys
130 135 140
Val Val Val Asp Val Ser His Glu Asp Pro Glu Val Lys Phe Asn Trp
145 150 155 160
Tyr Val Asp Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu
165 170 175
Glu Gln Tyr Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu
180 185 190
His Gln Asp Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn
195 200 205
Lys Ala Leu Pro Ala Pro Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly
210 215 220
Gln Pro Arg Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Arg Asp Glu
225 230 235 240
Leu Thr Lys Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr
245 250 255
Pro Ser Asp Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn
260 265 270
Asn Tyr Lys Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe
275 280 285
Leu Tyr Ser Lys Leu Thr Val Asp Lys Ser Arg Trp Gln Gln Gly Asn
290 295 300
Val Phe Ser Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr
305 310 315 320
Gln Lys Ser Leu Ser Leu Ser Pro Gly Lys Cys Asp Leu Pro Gln Thr
325 330 335
His Ser Leu Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg
340 345 350
Arg Ile Ser Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe
355 360 365
Pro Gln Glu Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro
370 375 380
Val Leu His Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys
385 390 395 400
Asp Ser Ser Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr
405 410 415
Glu Leu Tyr Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly
420 425 430
Val Gly Val Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala
435 440 445
Val Arg Lys Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys
450 455 460
Tyr Ser Pro Cys Ala Trp Glu Val Val Arg Gly Glu Ile Met Arg Ser
465 470 475 480
Phe Ser Leu Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490 495
<210> 658
<211> 492
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 658
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys Cys Asp Leu Pro Gln Thr His Ser Leu
325 330 335
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
340 345 350
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
355 360 365
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
370 375 380
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
385 390 395 400
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
405 410 415
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
420 425 430
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
435 440 445
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
450 455 460
Cys Ala Trp Glu Val Val Arg Asp Glu Ile Met Arg Ser Phe Ser Leu
465 470 475 480
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490
<210> 659
<211> 121
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<220>
<221> 变体
<222> (42)..(42)
<223> X = His 或 Pro
<220>
<221> 变体
<222> (76)..(76)
<223> X = Ser 或 Leu
<220>
<221> 变体
<222> (80)..(80)
<223> X = Phe 或 Ile
<220>
<221> 变体
<222> (83)..(83)
<223> X = Lys 或 Arg
<220>
<221> 变体
<222> (85)..(85)
<223> X = Ser 和 Thr
<220>
<221> 变体
<222> (108)..(108)
<223> X = Leu 或 Met
<400> 659
Gln Leu Gln Leu Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Glu
1 5 10 15
Thr Leu Ser Leu Thr Cys Thr Val Ser Gly Gly Ser Ile Ser Ser Ser
20 25 30
Ser Tyr Tyr Trp Ser Trp Ile Arg Gln Xaa Pro Gly Lys Gly Leu Glu
35 40 45
Trp Ile Gly Tyr Ile Tyr Tyr Ser Gly Ser Thr Asn Tyr Asn Pro Ser
50 55 60
Leu Lys Ser Arg Val Thr Ile Ser Val Asp Thr Xaa Lys Asn Gln Xaa
65 70 75 80
Ser Leu Xaa Leu Xaa Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Tyr
85 90 95
Cys Ala Arg Val Gly Gly Ala Gly Gly Trp Pro Xaa Asp Val Trp Gly
100 105 110
Gln Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 660
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 660
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 661
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 661
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Glu Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 662
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 662
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 663
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 663
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Gln Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 664
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<220>
<221> 变体
<222> (31)..(31)
<223> X = Arg 或 Gly
<220>
<221> 变体
<222> (32)..(32)
<223> X = Tyr 或 Ser
<220>
<221> 变体
<222> (54)..(54)
<223> X = Ser 或 Glu 或 Gln
<220>
<221> 变体
<222> (77)..(77)
<223> X = Asn 或 Thr
<220>
<221> 变体
<222> (97)..(97)
<223> X = Met 或 Leu
<220>
<221> 变体
<222> (102)..(102)
<223> X = Asn 或 Gln 或 Glu
<400> 664
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Xaa Xaa
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Xaa Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Xaa Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Xaa Thr Trp Ser Ser Xaa Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 665
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<220>
<221> 变体
<222> (1)..(1)
<223> X= Glu 或 Gln
<220>
<221> 变体
<222> (17)..(17)
<223> X= Thr 或 Ser
<220>
<221> 变体
<222> (20)..(20)
<223> X= Ile 或 Val
<220>
<221> 变体
<222> (29)..(29)
<223> X= Phe 或 Leu
<220>
<221> 变体
<222> (38)..(38)
<223> X= Gln 或 Arg
<220>
<221> 变体
<222> (40)..(40)
<223> X=Glu 或 Gly 或 His 或 Ala
<220>
<221> 变体
<222> (62)..(62)
<223> X=Glu 或 Gln
<220>
<221> 变体
<222> (70)..(70)
<223> X=Ile 或 Met
<220>
<221> 变体
<222> (100)..(100)
<223> X=Lys 或 Gly 或 Thr
<220>
<221> 变体
<222> (102)..(102)
<223> X=Asn 或 Gln
<400> 665
Xaa Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Xaa Val Lys Xaa Ser Cys Lys Val Ser Gly Tyr Thr Xaa Thr Asp Ser
20 25 30
Val Met Asn Trp Val Xaa Gln Xaa Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Xaa Lys Phe
50 55 60
Gln Gly Arg Val Thr Xaa Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Xaa Tyr Xaa Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 666
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<220>
<221> 变体
<222> (24)..(24)
<223> X = Lys 或 Gly 或 Gln
<220>
<221> 变体
<222> (53)..(53)
<223> X = Asn 或 Gln
<220>
<221> 变体
<222> (54)..(54)
<223> X = Arg 或 Asp
<220>
<221> 变体
<222> (89)..(89)
<223> X = Met 或 Ala
<400> 666
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 Xaa Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Xaa Xaa Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Xaa Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 667
<211> 363
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 667
cagctgcagc tgcaggaatc cggccctggc ctggtcaagc cctccgagac actgagcctg 60
acctgcaccg tgtccggcgg ctccatctcc tccagctcct actactggtc ctggatccgg 120
cagcaccccg gcaagggcct ggaatggatc ggctacatct actactccgg ctccaccaac 180
tacaacccca gcctgaagtc cagagtgacc atctccgtgg acacctccaa gaaccagttc 240
tccctgaagc tgtcctccgt gaccgccgct gacaccgccg tgtactactg tgccagagtg 300
ggcggagctg gcggctggcc tctggatgtg tggggccagg gcaccaccgt caccgtgtcc 360
tca 363
<210> 668
<211> 363
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 668
cagctgcagc tgcaggaatc cggccctggc ctggtcaagc cctccgagac actgagcctg 60
acctgcaccg tgtccggcgg ctccatctcc tccagctcct actactggtc ctggatccgg 120
cagcctcccg gcaagggcct ggaatggatc ggctacatct actactccgg ctccaccaac 180
tacaacccca gcctgaagtc cagagtgacc atctccgtgg acaccctgaa gaaccagatc 240
tccctgcggc tgacctccgt gaccgccgct gacaccgccg tgtactactg tgccagagtg 300
ggcggagctg gcggctggcc tatggatgtg tggggccagg gcaccaccgt caccgtgtcc 360
tca 363
<210> 669
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 669
caggccgtgc tgacccagcc tgcctccctg tctgcctctc ctggcgagtc cgccagactg 60
acctgcaccc tgccctccga catcaacgtg cggtactaca acatctactg gtatcagcag 120
aagcccggca gcccccccag atacctgctg tactactact ccgactccca caagggccag 180
ggctccggcg tgccctccag attctccggc tccaaggacg tgtccaccaa ctccggcatc 240
ctgctgatct ccggcctgca gtccgaggac attgccacct actactgcat gacttggagc 300
agcaacggca gcggcgtgtt cggcggaggc acccagctga ccgtcctagg t 351
<210> 670
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 670
caggccgtgc tgacccagcc tgcctccctg tctgcctctc ctggcgagtc cgccagactg 60
acctgcaccc tgccctccga catcaacgtg cggtactaca acatctactg gtatcagcag 120
aagcccggca gcccccccag atacctgctg tactactact ccgactccca caagggccag 180
ggctccggcg tgccctccag attctccggc tccaaggacg tgtccaccac ctccggcatc 240
ctgctgatct ccggcctgca gtccgaggac attgccacct actactgcat gacttggagc 300
agcaacggca gcggcgtgtt cggcggaggc acccagctga ccgtcctagg t 351
<210> 671
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 671
caggccgtgc tgacccagcc tgcctccctg tctgcctctc ctggcgagtc cgccagactg 60
acctgcaccc tgccctccga catcaacgtg cggtactaca acatctactg gtatcagcag 120
aagcccggca gcccccccag atacctgctg tactactacg aggactccca caagggccag 180
ggctccggcg tgccctccag attctccggc tccaaggacg tgtccaccaa ctccggcatc 240
ctgctgatct ccggcctgca gtccgaggac attgccacct actactgcat gacttggagc 300
agcaacggca gcggcgtgtt cggcggaggc acccagctga ccgtcctagg t 351
<210> 672
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 672
caggccgtgc tgacccagcc tgcctccctg tctgcctctc ctggcgagtc cgccagactg 60
acctgcaccc tgccctccga catcaacgtg cggtactaca acatctactg gtatcagcag 120
aagcccggca gcccccccag atacctgctg tactactacc aggactccca caagggccag 180
ggctccggcg tgccctccag attctccggc tccaaggacg tgtccaccaa ctccggcatc 240
ctgctgatct ccggcctgca gtccgaggac attgccacct actactgcat gacttggagc 300
agcaacggca gcggcgtgtt cggcggaggc acccagctga ccgtcctagg t 351
<210> 673
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 673
caggctgtgc tgacgcagcc ggccagcctc tccgcgtccc ctggcgaatc cgcacggctg 60
acttgcaccc tgccgagcga cattaacgtc ggtagctaca atatctactg gtaccaacaa 120
aagccgggga gcccaccccg ctacttactg tattactact cggattccca taaaggacag 180
ggatcgggag tgccatcacg cttcagcgga tcgaaggatg tgtcgaccaa ttcgggaatc 240
ctgctcatct caggcttgca gagcgaggac atcgccacct actactgtct gacttggtca 300
tcccaggggt caggcgtgtt tggaggaggt acccagctga ctgtcctagg t 351
<210> 674
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 674
caggctgtgc tgacgcagcc ggccagcctc tccgcgtccc ctggcgaatc cgcacggctg 60
acttgcaccc tgccgagcga cattaacgtc ggtagctaca atatctactg gtaccaacaa 120
aagccgggga gcccaccccg ctacttactg tattactact cggattccca taaaggacag 180
ggatcgggag tgccatcacg cttcagcgga tcgaaggatg tgtcgaccaa ttcgggaatc 240
ctgctcatct caggcttgca gagcgaggac atcgccacct actactgtct gacttggtca 300
tccgaagggt caggcgtgtt tggaggaggt acccagctga ctgtcctagg t 351
<210> 675
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 675
caggctgtgc tgacgcagcc ggccagcctc tccgcgtccc ctggcgaatc cgcacggctg 60
acttgcaccc tgccgagcga cattaacgtc ggtagctaca atatctactg gtaccaacaa 120
aagccgggga gcccaccccg ctacttactg tattactacg aggattccca taaaggacag 180
ggatcgggag tgccatcacg cttcagcgga tcgaaggatg tgtcgaccac ctcgggaatc 240
ctgctcatct caggcttgca gagcgaggac atcgccacct actactgtct gacttggtca 300
tcccaggggt caggcgtgtt tggaggaggt acccagctga ctgtcctagg t 351
<210> 676
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 676
caggctgtgc tgacgcagcc ggccagcctc tccgcgtccc ctggcgaatc cgcacggctg 60
acttgcaccc tgccgagcga cattaacgtc ggtagctaca atatctactg gtaccaacaa 120
aagccgggga gcccaccccg ctacttactg tattactacg aggattccca taaaggacag 180
ggatcgggag tgccatcacg cttcagcgga tcgaaggatg tgtcgaccac ctcgggaatc 240
ctgctcatct caggcttgca gagcgaggac atcgccacct actactgtct gacttggtca 300
tccgaagggt caggcgtgtt tggaggaggt acccagctga ctgtcctagg t 351
<210> 677
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 677
caggctgtgc tgacgcagcc ggccagcctc tccgcgtccc ctggcgaatc cgcacggctg 60
acttgcaccc tgccgagcga cattaacgtc ggtagctaca atatctactg gtaccaacaa 120
aagccgggga gcccaccccg ctacttactg tattactacc aggattccca taaaggacag 180
ggatcgggag tgccatcacg cttcagcgga tcgaaggatg tgtcgaccac ctcgggaatc 240
ctgctcatct caggcttgca gagcgaggac atcgccacct actactgtct gacttggtca 300
tcccaggggt caggcgtgtt tggaggaggt acccagctga ctgtcctagg t 351
<210> 678
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 678
caggctgtgc tgacgcagcc ggccagcctc tccgcgtccc ctggcgaatc cgcacggctg 60
acttgcaccc tgccgagcga cattaacgtc ggtagctaca atatctactg gtaccaacaa 120
aagccgggga gcccaccccg ctacttactg tattactacc aggattccca taaaggacag 180
ggatcgggag tgccatcacg cttcagcgga tcgaaggatg tgtcgaccac ctcgggaatc 240
ctgctcatct caggcttgca gagcgaggac atcgccacct actactgtct gacttggtca 300
tccgaagggt caggcgtgtt tggaggaggt acccagctga ctgtcctagg t 351
<210> 679
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 679
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcaggag 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 680
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 680
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcagggc 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 681
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 681
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcagcac 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 682
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 682
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcagcag 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 683
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 683
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcaggcc 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccggc 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 684
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 684
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcaggcc 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccacc 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 685
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 685
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcaggcc 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 686
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 686
gaggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgctac cgtgaagatc 60
tcctgcaagg tgtccggcta caccttcacc gactccgtga tgaactgggt gcagcaggcc 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gccgagaagt tccagggcag agtgaccatc accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccctaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac agtgtcctca 360
<210> 687
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 687
caggtgcagc tggtgcagtc cggcgctgaa gtgaagaaac ccggcgcttc cgtgaaggtg 60
tcctgcaagg tgtccggcta caccctgacc gactccgtga tgaactgggt gcgacaggcc 120
cctggcaagg gcctggaatg gatgggctgg atcgaccccg agtacggcag aaccgacgtg 180
gcccagaaat tccagggcag agtgaccatg accgccgaca cctccaccga caccgcctac 240
atggaactgt cctccctgcg gagcgaggac accgccgtgt actactgcgc ccggaccaag 300
tacaactccg gctacggctt cccctactgg ggccagggca ccaccgtgac cgtgtcctca 360
<210> 688
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 688
gacatccaga tgacccagag cccttccagc ctgtccgcct ctgtgggcga cagagtgacc 60
atcacatgca aggcctccca gaacgtggac agcgacgtgg actggtatca gcagaagccc 120
ggcaaggccc ctaagctgct gatctacaag gccagcaaca gatacaccgg cgtgccctcc 180
agattctccg gctctggatc tggcaccgac ttcaccttca ccatcagctc cctgcagccc 240
gaggacattg ccacctacta ctgtatgcag tccaacaccc acccccggac cttcggcgga 300
ggcaccaagg tggaaatcaa gcgt 324
<210> 689
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 689
gacatccaga tgacccagag cccttccagc ctgtccgcct ctgtgggcga cagagtgacc 60
atcacatgcg gcgcctccca gaacgtggac agcgacgtgg actggtatca gcagaagccc 120
ggcaaggccc ctaagctgct gatctacaag gccagcaaca gatacaccgg cgtgccctcc 180
agattctccg gctctggatc tggcaccgac ttcaccttca ccatcagctc cctgcagccc 240
gaggacattg ccacctacta ctgtatgcag tccaacaccc acccccggac cttcggcgga 300
ggcaccaagg tggaaatcaa gcgt 324
<210> 690
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 690
gacatccaga tgacccaatc cccttcctca ttgtccgctt cggtcggcga ccgcgtgact 60
atcacttgcc aggcatcaca aaacgtggat tcggatgtgg attggtacca gcagaagccc 120
ggaaaggccc cgaaactgct gatctacaag gcgtccaacc ggtacactgg cgtcccgtcg 180
agattcagcg gaagcgggtc gggaaccgac tttaccttca ctatcagctc actccagcca 240
gaggacattg ccacctatta ctgtatgcag agcaataccc acccgcgcac cttcggagga 300
ggtactaaag tggaaatcaa gcgt 324
<210> 691
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 691
gacatccaga tgacccagag cccttccagc ctgtccgcct ctgtgggcga cagagtgacc 60
atcacatgca aggcctccca gaacgtggac agcgacgtgg actggtatca gcagaagccc 120
ggcaaggccc ctaagctgct gatctacaag gccagcaacg actacaccgg cgtgccctcc 180
agattctccg gctctggatc tggcaccgac ttcaccttca ccatcagctc cctgcagccc 240
gaggacattg ccacctacta ctgtatgcag tccaacaccc acccccggac cttcggcgga 300
ggcaccaagg tggaaatcaa gcgt 324
<210> 692
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 692
gacatccaga tgacccagag cccttccagc ctgtccgcct ctgtgggcga cagagtgacc 60
atcacatgca aggcctccca gaacgtggac agcgacgtgg actggtatca gcagaagccc 120
ggcaaggccc ctaagctgct gatctacaag gccagcaaca gatacaccgg cgtgccctcc 180
agattctccg gctctggatc tggcaccgac ttcaccttca ccatcagctc cctgcagccc 240
gaggacattg ccacctacta ctgtgcgcag tccaacaccc acccccggac cttcggcgga 300
ggcaccaagg tggaaatcaa gcgt 324
<210> 693
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的。
<400> 693
gacatccaga tgacccaatc cccttcctca ttgtccgctt cggtcggcga ccgcgtgact 60
atcacttgca aagcatcaca aaacgtggat tcggatgtgg attggtacca gcagaagccc 120
ggaaaggccc cgaaactgct gatctacaag gcgtcccagc ggtacactgg cgtcccgtcg 180
agattcagcg gaagcgggtc gggaaccgac tttaccttca ctatcagctc actccagcca 240
gaggacattg ccacctatta ctgtatgcag agcaataccc acccgcgcac cttcggagga 300
ggtactaaag tggaaatcaa gcgt 324
<210> 694
<211> 492
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的。
<400> 694
Ala Ser Thr Lys Gly Pro Ser Val Phe Pro Leu Ala Pro Cys Ser Arg
1 5 10 15
Ser Thr Ser Glu Ser Thr Ala Ala Leu Gly Cys Leu Val Lys Asp Tyr
20 25 30
Phe Pro Glu Pro Val Thr Val Ser Trp Asn Ser Gly Ala Leu Thr Ser
35 40 45
Gly Val His Thr Phe Pro Ala Val Leu Gln Ser Ser Gly Leu Tyr Ser
50 55 60
Leu Ser Ser Val Val Thr Val Pro Ser Ser Ser Leu Gly Thr Lys Thr
65 70 75 80
Tyr Thr Cys Asn Val Asp His Lys Pro Ser Asn Thr Lys Val Asp Lys
85 90 95
Arg Val Glu Ser Lys Tyr Gly Pro Pro Cys Pro Pro Cys Pro Ala Pro
100 105 110
Glu Phe Leu Gly Gly Pro Ser Val Phe Leu Phe Pro Pro Lys Pro Lys
115 120 125
Asp Thr Leu Tyr Ile Thr Arg Glu Pro Glu Val Thr Cys Val Val Val
130 135 140
Asp Val Ser Gln Glu Asp Pro Glu Val Gln Phe Asn Trp Tyr Val Asp
145 150 155 160
Gly Val Glu Val His Asn Ala Lys Thr Lys Pro Arg Glu Glu Gln Phe
165 170 175
Asn Ser Thr Tyr Arg Val Val Ser Val Leu Thr Val Leu His Gln Asp
180 185 190
Trp Leu Asn Gly Lys Glu Tyr Lys Cys Lys Val Ser Asn Lys Gly Leu
195 200 205
Pro Ser Ser Ile Glu Lys Thr Ile Ser Lys Ala Lys Gly Gln Pro Arg
210 215 220
Glu Pro Gln Val Tyr Thr Leu Pro Pro Ser Gln Glu Glu Met Thr Lys
225 230 235 240
Asn Gln Val Ser Leu Thr Cys Leu Val Lys Gly Phe Tyr Pro Ser Asp
245 250 255
Ile Ala Val Glu Trp Glu Ser Asn Gly Gln Pro Glu Asn Asn Tyr Lys
260 265 270
Thr Thr Pro Pro Val Leu Asp Ser Asp Gly Ser Phe Phe Leu Tyr Ser
275 280 285
Arg Leu Thr Val Asp Lys Ser Arg Trp Gln Glu Gly Asn Val Phe Ser
290 295 300
Cys Ser Val Met His Glu Ala Leu His Asn His Tyr Thr Gln Lys Ser
305 310 315 320
Leu Ser Leu Ser Leu Gly Lys Cys Asp Leu Pro Gln Thr His Ser Leu
325 330 335
Gly Ser Arg Arg Thr Leu Met Leu Leu Ala Gln Met Arg Arg Ile Ser
340 345 350
Leu Phe Ser Cys Leu Lys Asp Arg His Asp Phe Gly Phe Pro Gln Glu
355 360 365
Glu Phe Gly Asn Gln Phe Gln Lys Ala Glu Thr Ile Pro Val Leu His
370 375 380
Glu Met Ile Gln Gln Ile Phe Asn Leu Phe Ser Thr Lys Asp Ser Ser
385 390 395 400
Ala Ala Trp Asp Glu Thr Leu Leu Asp Lys Phe Tyr Thr Glu Leu Tyr
405 410 415
Gln Gln Leu Asn Asp Leu Glu Ala Cys Val Ile Gln Gly Val Gly Val
420 425 430
Thr Glu Thr Pro Leu Met Lys Glu Asp Ser Ile Leu Ala Val Arg Lys
435 440 445
Tyr Phe Gln Arg Ile Thr Leu Tyr Leu Lys Glu Lys Lys Tyr Ser Pro
450 455 460
Cys Ala Trp Glu Val Val Arg Gly Glu Ile Met Arg Ser Phe Ser Leu
465 470 475 480
Ser Thr Asn Leu Gln Glu Ser Leu Arg Ser Lys Glu
485 490
<210> 695
<211> 366
<212> DNA
<213> 智人
<400> 695
gaggtccagc tggtacagtc tggggctgag gtgaagaagt ctggggcctc agtgaaggtc 60
tcctgcaagg cttctggata caccttcacc gactactata tacactgggt gcgacaggcc 120
cctggacaag ggcttgagtg gatgggatgg atcaacccta acaatggtgg cgtaaccttt 180
gcccagaagt ttcagggcag ggtcaccatg accagggaca cgtccatcag cacagcctac 240
atggacctga gcagcctgag atctgacgac acggccgtct acttctgtgc gagagatatt 300
cgaatgagcg ggtggctggc gccatttgac tactggggcc agggaaccct ggtcaccgtc 360
tcctca 366
<210> 696
<211> 11
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 696
Gly Ala Ser Gln Asn Val Asp Ser Asp Val Asp
1 5 10
<210> 697
<211> 5
<212> PRT
<213> 智人
<400> 697
Asp Tyr Tyr Ile His
1 5
<210> 698
<211> 17
<212> PRT
<213> 智人
<400> 698
Trp Ile Asn Pro Asn Asn Gly Gly Val Thr Phe Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 699
<211> 13
<212> PRT
<213> 智人
<400> 699
Asp Ile Arg Met Ser Gly Trp Leu Ala Pro Phe Asp Tyr
1 5 10
<210> 700
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 700
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Gln Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 701
<211> 117
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 701
Gln Ala Val Leu Thr Gln Pro Ala Ser Leu Ser Ala Ser Pro Gly Glu
1 5 10 15
Ser Ala Arg Leu Thr Cys Thr Leu Pro Ser Asp Ile Asn Val Gly Ser
20 25 30
Tyr Asn Ile Tyr Trp Tyr Gln Gln Lys Pro Gly Ser Pro Pro Arg Tyr
35 40 45
Leu Leu Tyr Tyr Tyr Ser Asp Ser His Lys Gly Gln Gly Ser Gly Val
50 55 60
Pro Ser Arg Phe Ser Gly Ser Lys Asp Val Ser Thr Thr Ser Gly Ile
65 70 75 80
Leu Leu Ile Ser Gly Leu Gln Ser Glu Asp Ile Ala Thr Tyr Tyr Cys
85 90 95
Leu Thr Trp Ser Ser Glu Gly Ser Gly Val Phe Gly Gly Gly Thr Gln
100 105 110
Leu Thr Val Leu Gly
115
<210> 702
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 702
caagccgtcc tgactcagcc agccagcctg tccgcgtcac cgggagaatc cgctcgcctg 60
acttgcactc tgccctcaga catcaatgtc ggttcgtaca acatctactg gtaccaacaa 120
aagccggggt cgcctccgcg gtatctgttg tactactact cggatagcca caagggacag 180
ggctcgggag tgccatccag attttccggg tcaaaagatg tgagcacgac ctcgggcatc 240
ctcctcatca gcggacttca gtccgaggac attgcgacct actactgcct cacttggtcg 300
tcacagggaa gcggagtgtt cggaggaggc acccagctga ccgtcctagg t 351
<210> 703
<211> 351
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 703
caagccgtcc tgactcagcc agccagcctg tccgcgtcac cgggagaatc cgctcgcctg 60
acttgcactc tgccctcaga catcaatgtc ggttcgtaca acatctactg gtaccaacaa 120
aagccggggt cgcctccgcg gtatctgttg tactactact cggatagcca caagggacag 180
ggctcgggag tgccatccag attttccggg tcaaaagatg tgagcacgac ctcgggcatc 240
ctcctcatca gcggacttca gtccgaggac attgcgacct actactgcct cacttggtcg 300
tcagaaggaa gcggagtgtt cggaggaggc acccagctga ccgtcctagg t 351
<210> 704
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 704
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 Gly Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Asp Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 705
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 705
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 Gly Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 706
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 706
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 Gln Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Asp Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 707
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 707
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 Gln Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Asn Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 708
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 708
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 Gly Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Gln Asp Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 709
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 709
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 Gly Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Gln Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 710
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 710
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 Gln Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Gln Asp Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 711
<211> 108
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 711
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 Gln Ala Ser Gln Asn Val Asp Ser Asp
20 25 30
Val Asp Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile
35 40 45
Tyr Lys Ala Ser Gln Arg Tyr Thr Gly Val Pro Ser Arg Phe Ser Gly
50 55 60
Ser Gly Ser Gly Thr Asp Phe Thr Phe Thr Ile Ser Ser Leu Gln Pro
65 70 75 80
Glu Asp Ile Ala Thr Tyr Tyr Cys Ala Gln Ser Asn Thr His Pro Arg
85 90 95
Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Arg
100 105
<210> 712
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 712
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtg gcgcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctccaatg attacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 713
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 713
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtg gcgcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctccaatc gctacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 714
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 714
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtc aggcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctccaatg attacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 715
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 715
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtc aggcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctccaatc gctacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 716
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 716
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtg gcgcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctcccagg attacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 717
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 717
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtg gcgcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctcccagc gctacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 718
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 718
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtc aggcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctcccagg attacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 719
<211> 324
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 719
gacatccaga tgactcagag cccgtcctcg ctttcggctt ccgtcggcga ccgcgtgacc 60
atcacttgtc aggcgtcgca gaacgtcgat tccgacgtgg actggtacca acagaagccg 120
gggaaagcgc ccaagctgct gatctacaag gcctcccagc gctacactgg agtgcctagc 180
cggttcagcg gatcagggtc gggaacggac ttcactttta ccatctcaag cctccaacca 240
gaagatattg ccacctatta ctgcgcacaa tcaaacaccc acccgagaac cttcggcgga 300
ggaaccaagg tggagatcaa acgt 324
<210> 720
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 720
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Gly Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 721
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 721
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln His Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 722
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 722
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln Gly Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Gln Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 723
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 723
Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Val Ser Gly Tyr Thr Leu Thr Asp Ser
20 25 30
Val Met Asn Trp Val Arg Gln His Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Gln Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 724
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 724
caagtgcaac tggtgcagtc cggtgccgaa gtgaagaaac cgggtgcgtc cgtcaaagtg 60
agctgcaagg tgtccgggta caccttgact gattcagtga tgaattgggt gcggcagggg 120
ccaggaaagg gactggagtg gatgggatgg atcgaccctg aatacggaag gactgacgtc 180
gcccagaagt ttcagggacg cgtcacgatg actgccgata cttcgaccga cacggcttac 240
atggaactct cgtccctgag atcggaggac accgcagtct actactgtgc tcgcactggc 300
tataactcag gctacggctt cccgtactgg ggacaaggaa ccaccgtgac agtgtcctca 360
<210> 725
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 725
caagtgcaac tggtgcagtc cggtgccgaa gtgaagaaac cgggtgcgtc cgtcaaagtg 60
agctgcaagg tgtccgggta caccttgact gattcagtga tgaattgggt gcggcagcac 120
ccaggaaagg gactggagtg gatgggatgg atcgaccctg aatacggaag gactgacgtc 180
gcccagaagt ttcagggacg cgtcacgatg actgccgata cttcgaccga cacggcttac 240
atggaactct cgtccctgag atcggaggac accgcagtct actactgtgc tcgcactggc 300
tataactcag gctacggctt cccgtactgg ggacaaggaa ccaccgtgac agtgtcctca 360
<210> 726
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 726
caagtgcaac tggtgcagtc cggtgccgaa gtgaagaaac cgggtgcgtc cgtcaaagtg 60
agctgcaagg tgtccgggta caccttgact gattcagtga tgaattgggt gcggcagggg 120
ccaggaaagg gactggagtg gatgggatgg atcgaccctg aatacggaag gactgacgtc 180
gcccagaagt ttcagggacg cgtcacgatg actgccgata cttcgaccga cacggcttac 240
atggaactct cgtccctgag atcggaggac accgcagtct actactgtgc tcgcactggc 300
tatcagtcag gctacggctt cccgtactgg ggacaaggaa ccaccgtgac agtgtcctca 360
<210> 727
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 727
caagtgcaac tggtgcagtc cggtgccgaa gtgaagaaac cgggtgcgtc cgtcaaagtg 60
agctgcaagg tgtccgggta caccttgact gattcagtga tgaattgggt gcggcagcac 120
ccaggaaagg gactggagtg gatgggatgg atcgaccctg aatacggaag gactgacgtc 180
gcccagaagt ttcagggacg cgtcacgatg actgccgata cttcgaccga cacggcttac 240
atggaactct cgtccctgag atcggaggac accgcagtct actactgtgc tcgcactggc 300
tatcagtcag gctacggctt cccgtactgg ggacaaggaa ccaccgtgac agtgtcctca 360
<210> 728
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 728
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Pro Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Asn Gly Gly Val Thr Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Asp Ile Arg Met Ser Gly Trp Leu Ala Pro Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 729
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 729
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Pro Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Asn Gly Gly Val Thr Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Asp Ile Arg Met Ser Gly Trp Leu Ala Pro Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 730
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 730
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Pro Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Asn Gly Gly Thr Thr Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Asp Ile Arg Met Ser Gly Trp Leu Ala Pro Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 731
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 731
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Pro Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Asn Gly Gly Val Thr Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Phe Cys
85 90 95
Ala Arg Asp Ile Arg Leu Ser Gly Trp Leu Ala Pro Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 732
<211> 366
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 732
gaagtccaac tggtccagtc gggcgcagag gtgaagaagt caggggcgag cgtgaaagtg 60
tcatgtaaag cctccggcta cacttttacc gattactaca ttcactgggt gagacagcct 120
ccgggacaag gactcgaatg gatgggctgg atcaatccaa acaacggagg tgtcaccttc 180
gctcagaagt tccaaggtcg ggtgaccatg acccgcgaca cgtcaatcag cactgcctac 240
atggatttgt cgtccctgcg gtccgatgac actgcggtgt acttctgcgc aagggacatc 300
cgcatgtcgg ggtggctggc cccgttcgac tattggggac agggaactct cgtgacagtg 360
tcctca 366
<210> 733
<211> 366
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 733
gaagtccaac tggtccagtc gggcgcagag gtgaagaagt caggggcgag cgtgaaagtg 60
tcatgtaaag cctccggcta cacttttacc gattactaca ttcactgggt gagacagcct 120
ccgggacaag gactcgaatg gatgggctgg atcaatccaa acaacggagg tgtcaccttc 180
gctcagaagt tccaaggtcg ggtgaccatg acccgcgaca cgtcaatcag cactgcctac 240
atggatttgt cgtccctgcg gtccgatgac actgcggtgt actactgcgc aagggacatc 300
cgcatgtcgg ggtggctggc cccgttcgac tattggggac agggaactct cgtgacagtg 360
tcctca 366
<210> 734
<211> 366
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 734
gaagtccaac tggtccagtc gggcgcagag gtgaagaagt caggggcgag cgtgaaagtg 60
tcatgtaaag cctccggcta cacttttacc gattactaca ttcactgggt gagacagcct 120
ccgggacaag gactcgaatg gatgggctgg atcaatccaa acaacggagg taccaccttc 180
gctcagaagt tccaaggtcg ggtgaccatg acccgcgaca cgtcaatcag cactgcctac 240
atggatttgt cgtccctgcg gtccgatgac actgcggtgt acttctgcgc aagggacatc 300
cgcatgtcgg ggtggctggc cccgttcgac tattggggac agggaactct cgtgacagtg 360
tcctca 366
<210> 735
<211> 366
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 735
gaagtccaac tggtccagtc gggcgcagag gtgaagaagt caggggcgag cgtgaaagtg 60
tcatgtaaag cctccggcta cacttttacc gattactaca ttcactgggt gagacagcct 120
ccgggacaag gactcgaatg gatgggctgg atcaatccaa acaacggagg tgtcaccttc 180
gctcagaagt tccaaggtcg ggtgaccatg acccgcgaca cgtcaatcag cactgcctac 240
atggatttgt cgtccctgcg gtccgatgac actgcggtgt acttctgcgc aagggacatc 300
cgcctgtcgg ggtggctggc cccgttcgac tattggggac agggaactct cgtgacagtg 360
tcctca 366
<210> 736
<211> 122
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<220>
<221> 变体
<222> (40)..(40)
<223> X = Ala 或 Pro
<220>
<221> 变体
<222> (58)..(58)
<223> X = Val 或 Thr
<220>
<221> 变体
<222> (95)..(95)
<223> X = Phe 或 Tyr
<220>
<221> 变体
<222> (102)..(102)
<223> X = Met 或 Leu
<400> 736
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asp Tyr
20 25 30
Tyr Ile His Trp Val Arg Gln Xaa Pro Gly Gln Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asn Pro Asn Asn Gly Gly Xaa Thr Phe Ala Gln Lys Phe
50 55 60
Gln Gly Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr
65 70 75 80
Met Asp Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Xaa Cys
85 90 95
Ala Arg Asp Ile Arg Xaa Ser Gly Trp Leu Ala Pro Phe Asp Tyr Trp
100 105 110
Gly Gln Gly Thr Leu Val Thr Val Ser Ser
115 120
<210> 737
<211> 17
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 737
Trp Ile Asn Pro Asn Asn Gly Gly Thr Thr Phe Ala Gln Lys Phe Gln
1 5 10 15
Gly
<210> 738
<211> 13
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 738
Asp Ile Arg Leu Ser Gly Trp Leu Ala Pro Phe Asp Tyr
1 5 10
<210> 739
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 739
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Gly Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 740
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 740
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln His Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Asn Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 741
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 741
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln Gly Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Gln Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 742
<211> 120
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 742
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala
1 5 10 15
Thr Val Lys Ile Ser Cys Lys Val Ser Gly Tyr Thr Phe Thr Asp Ser
20 25 30
Val Met Asn Trp Val Gln Gln His Pro Gly Lys Gly Leu Glu Trp Met
35 40 45
Gly Trp Ile Asp Pro Glu Tyr Gly Arg Thr Asp Val Ala Glu Lys Phe
50 55 60
Gln Gly Arg Val Thr Ile Thr Ala Asp Thr Ser Thr Asp Thr Ala Tyr
65 70 75 80
Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys
85 90 95
Ala Arg Thr Gly Tyr Gln Ser Gly Tyr Gly Phe Pro Tyr Trp Gly Gln
100 105 110
Gly Thr Thr Val Thr Val Ser Ser
115 120
<210> 743
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 743
gaagtgcagc tggtgcagtc gggtgcagag gtcaagaaac cgggagcgac cgtgaaaatc 60
agctgcaagg tgtccgggta cactttcacg gactcggtga tgaattgggt ccaacaggga 120
ccggggaagg gattggagtg gatgggatgg attgacccag aatacggccg caccgacgtc 180
gcagaaaagt ttcaaggacg ggtcactatc accgcggaca cctcaaccga tactgcctac 240
atggagctct cctcgctgag aagcgaagat actgccgtgt actactgtgc caggaccggt 300
tacaactcgg gatacggctt cccttattgg ggacagggca ccactgtgac agtgtcctca 360
<210> 744
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 744
gaggtgcagc tggtccagtc aggagcagaa gtcaaaaagc cgggagccac cgtcaagatt 60
tcgtgtaagg tgtcgggcta cactttcact gattccgtca tgaattgggt gcagcaacac 120
ccagggaaag ggttggaatg gatgggatgg atcgaccctg aatacggccg caccgacgtg 180
gcggagaagt ttcaaggaag agtgacgatc actgccgata cctcgaccga caccgcatac 240
atggaactga gctcgctccg gtccgaggac accgccgtgt actactgcgc gaggactggc 300
tacaacagcg gatacggatt cccgtattgg ggccagggta ccactgtgac agtgtcctca 360
<210> 745
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 745
gaggtccagc tggtgcaatc aggagccgaa gtgaaaaagc cgggagcaac cgtcaagatt 60
agctgtaagg tgtcggggta caccttcact gactccgtga tgaactgggt gcagcaaggg 120
ccaggaaagg gactggagtg gatgggctgg atcgaccctg aatacggcag gactgacgtc 180
gccgagaaat tccagggtag agtgaccatc actgcggata cctcgaccga cactgcgtac 240
atggaactct ccagcttgcg gtcggaagat accgccgtct actactgcgc acgcaccggt 300
tatcagtcgg gctacggatt tccgtactgg ggacaaggaa ctacggtgac agtgtcctca 360
<210> 746
<211> 360
<212> DNA
<213> 人工序列
<220>
<223> 完全合成的
<400> 746
gaagtccagc tcgtgcagtc gggagccgaa gtgaagaagc cgggagcgac tgtcaagatt 60
tcgtgtaagg tcagcggata taccttcacc gattccgtga tgaactgggt gcagcagcac 120
ccaggcaaag gccttgagtg gatggggtgg atcgacccgg agtacgggag aaccgacgtg 180
gcagagaaat ttcaaggacg ggtcaccatc actgccgaca cttccactga cactgcatac 240
atggaactgt catcgctgcg ctcggaagat accgccgtgt actactgcgc gaggacgggt 300
taccaaagcg gatacggatt cccttactgg ggccaaggta ccaccgtgac agtgtcctca 360
<210> 747
<211> 7
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 747
Lys Ala Ser Gln Asp Tyr Thr
1 5
<210> 748
<211> 30
<212> PRT
<213> 智人
<400> 748
Glu Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Ser Gly Ala
1 5 10 15
Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr
20 25 30
<210> 749
<211> 14
<212> PRT
<213> 智人
<400> 749
Trp Val Arg Gln Ala Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10
<210> 750
<211> 14
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 750
Trp Val Arg Gln Pro Pro Gly Gln Gly Leu Glu Trp Met Gly
1 5 10
<210> 751
<211> 32
<212> PRT
<213> 智人
<400> 751
Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Asp
1 5 10 15
Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Phe Cys Ala Arg
20 25 30
<210> 752
<211> 32
<212> PRT
<213> 人工序列
<220>
<223> 完全合成的
<400> 752
Arg Val Thr Met Thr Arg Asp Thr Ser Ile Ser Thr Ala Tyr Met Asp
1 5 10 15
Leu Ser Ser Leu Arg Ser Asp Asp Thr Ala Val Tyr Tyr Cys Ala Arg
20 25 30
<210> 753
<211> 11
<212> PRT
<213> 智人
<400> 753
Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser
1 5 10
Claims (17)
1.特异地结合CD38的抗体，其中所述抗体包括：
氨基酸序列为SEQ ID NO:514的重链CDR1，氨基酸序列为SEQ ID NO:516的重链CDR2，氨基酸序列为SEQ ID NO:518的重链CDR3，氨基酸序列为SEQ ID NO:608的轻链CDR1，氨基酸序列为SEQ ID NO:591的轻链CDR2，以及氨基酸序列为SEQ ID NO:612的轻链CDR3。
2.根据权利要求1所述的抗体，所述抗体包括一重链可变区和一轻链可变区，所述重链可变区包括氨基酸序列SEQ ID NO:156，所述轻链可变区包括氨基酸序列SEQ ID NO:185。
3.根据前述权利要求1或2所述的抗体，其中所述抗体包括人IgG1重链恒定区。
4.根据权利要求1或2所述的抗体，其中所述抗体包括人IgG4重链恒定区。
5.根据权利要求4所述的抗体，其中所述人IgG4重链恒定区包括根据EU编号体系在位置228处的脯氨酸。
6.根据权利要求5所述的抗体，其中所述人IgG4重链恒定区包括根据EU编号体系在所述恒定区的位置252处的酪氨酸、位置254处的苏氨酸和位置256处的谷氨酸。
7.根据权利要求1或5到6任一项所述的抗体，其中所述抗体是人源化抗体。
8.一种抗-CD38抗体-致弱干扰素α-2b融合蛋白，其包括权利要求1到7任一项所述的抗体；和致弱干扰素α-2b。
9.根据权利要求8所述的蛋白，其中所述致弱干扰素α-2b包括在对应于氨基酸序列SEQID NO:648的位置145处的丙氨酸被天冬氨酸取代。
10.根据权利要求8或9所述的蛋白，其中所述致弱干扰素α-2b包括氨基酸序列SEQIDNO:647、SEQ ID NO:649、SEQ ID NO:650或SEQ ID NO:651。
11.一种组合物，其包括根据权利要求1到7任一项所述的抗体或权利要求8到10任一项所述的蛋白和药学上可接受的载体。
12.一种多核苷酸，其包括编码根据权利要求1到7任一项所述的抗体或根据权利要求8到10任一项所述的蛋白的核酸序列。
13.根据权利要求12所述的多核苷酸，其中编码所述抗体重链可变区的核酸序列包括SEQ ID NO:685，以及编码所述抗体轻链可变区的核酸序列包括SEQ ID NO:691。
14.一种载体，其包括多核苷酸，所述多核苷酸包括编码根据权利要求1到7任一项所述的抗体或根据权利要求8到10任一项所述的蛋白的核酸序列。
15.一种转化哺乳动物细胞，其包括权利要求14所述的载体。
16.根据权利要求1到7任一项所述的抗体或根据权利要求8到10任一项所述的蛋白在制备用于治疗肿瘤的药物中的用途。
17.根据权利要求16所述用途，其中所述肿瘤是B-细胞淋巴瘤、多发性骨髓瘤、非霍奇金淋巴瘤、慢性骨髓性白血病、慢性淋巴细胞白血病或急性骨髓性白血病。
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Families Citing this family (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102096224B1 (ko) | 2011-10-28 | 2020-04-03 | 테바 파마슈티컬즈 오스트레일리아 피티와이 엘티디 | 폴리펩티드 구축물 및 이의 용도 |
| CN104470536A (zh) | 2012-03-03 | 2015-03-25 | 免疫基因公司 | 工程化的抗体-干扰素突变体融合分子 |
| EP2900232B1 (en) | 2012-09-25 | 2017-11-15 | MorphoSys AG | Combinations and uses thereof |
| MX370377B (es) | 2013-04-29 | 2019-12-11 | Teva Pharmaceuticals Australia Pty Ltd | Anticuerpos anti-cd38 y fusiones con interferón alfa-2b atenuado. |
| US11117975B2 (en) | 2013-04-29 | 2021-09-14 | Teva Pharmaceuticals Australia Pty Ltd | Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B |
| US9603927B2 (en) * | 2014-02-28 | 2017-03-28 | Janssen Biotech, Inc. | Combination therapies with anti-CD38 antibodies |
| US9732154B2 (en) | 2014-02-28 | 2017-08-15 | Janssen Biotech, Inc. | Anti-CD38 antibodies for treatment of acute lymphoblastic leukemia |
| UA119352C2 (uk) | 2014-05-01 | 2019-06-10 | Тева Фармасьютикалз Острейліа Пті Лтд | Комбінація леналідоміду або помалідоміду і конструкції анти-cd38 антитіло-атенуйований інтерферон альфа-2b та спосіб лікування суб'єкта, який має cd38-експресуючу пухлину |
| WO2016040294A2 (en) | 2014-09-09 | 2016-03-17 | Janssen Biotech, Inc. | Combination therapies with anti-cd38 antibodies |
| JP6730271B2 (ja) | 2014-10-29 | 2020-07-29 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | インターフェロンα２Ｂバリアント |
| CA2969717A1 (en) | 2014-12-04 | 2016-06-09 | Janssen Biotech, Inc. | Anti-cd38 antibodies for treatment of acute myeloid leukemia |
| BR112017024877A2 (pt) | 2015-05-20 | 2019-09-17 | Janssen Biotech, Inc. | anticorpo anti-cd38 e seu uso no tratamento de amiloidose de cadeia leve e outras malignidades hematológicas positivas para cd38 |
| MX2018000265A (es) | 2015-06-22 | 2018-05-23 | Janssen Biotech Inc | Terapias de combinacion para enfermedades malignas hematologicas con anticuerpos anti-cd38 e inhibidores de survivina. |
| MD3313441T2 (ro) | 2015-06-24 | 2024-08-31 | Janssen Biotech Inc | Modularea imună și tratament al tumorilor solide cu anticorpi care leagă specific CD38 |
| US20170044265A1 (en) | 2015-06-24 | 2017-02-16 | Janssen Biotech, Inc. | Immune Modulation and Treatment of Solid Tumors with Antibodies that Specifically Bind CD38 |
| US20180155411A1 (en) * | 2015-07-08 | 2018-06-07 | The Board Of Trustees Of The Leland Stanford Junior University | Heterotypic antibodies specific for human rotavirus |
| PE20181365A1 (es) | 2015-11-03 | 2018-08-27 | Janssen Biotech Inc | Formulaciones subcutaneas de anticuerpos anti-cd38 y sus usos |
| US10781261B2 (en) | 2015-11-03 | 2020-09-22 | Janssen Biotech, Inc. | Subcutaneous formulations of anti-CD38 antibodies and their uses |
| SG11201806214RA (en) | 2016-03-04 | 2018-08-30 | Morphosys Ag | Clinical assessment of m-protein response in multiple myeloma |
| EP3474895A1 (en) | 2016-06-28 | 2019-05-01 | UMC Utrecht Holding B.V. | TREATMENT OF IgE-MEDIATED DISEASES WITH ANTIBODIES THAT SPECIFICALLY BIND CD38 |
| WO2018014068A1 (en) * | 2016-07-19 | 2018-01-25 | Teva Pharmaceuticals Australia Pty Ltd | Attenuated type i ifn cd47 combination therapy |
| JP7241677B2 (ja) * | 2016-07-19 | 2023-03-17 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | 抗ｃｄ４７併用療法 |
| WO2018015498A1 (en) | 2016-07-20 | 2018-01-25 | Hybrigenics Sa | Combinations of inecalcitol with an anti-cd38 agent and their uses for treating cancer |
| CA3031028C (en) * | 2016-07-25 | 2024-02-13 | Lu Wang | Affinity chromatography wash buffer |
| US11426706B2 (en) | 2017-06-21 | 2022-08-30 | Cephalon, Inc. | Cation exchange chromatography wash buffer |
| WO2019035938A1 (en) | 2017-08-16 | 2019-02-21 | Elstar Therapeutics, Inc. | MULTISPECIFIC MOLECULES BINDING TO BCMA AND USES THEREOF |
| WO2019089832A1 (en) | 2017-10-31 | 2019-05-09 | Janssen Biotech, Inc. | Methods of treating high risk multiple myeloma |
| JP6648171B2 (ja) * | 2018-02-02 | 2020-02-14 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | 抗ｃｄ３８抗体及び弱毒化インターフェロンアルファ−２ｂとの融合物 |
| MA53920A (fr) | 2018-10-17 | 2021-09-15 | Janssen Biotech Inc | Procédé de fourniture d'administration sous-cutanée d'anticorps anti-cd38 |
| CA3122902A1 (en) | 2018-12-14 | 2020-06-18 | Morphosys Ag | Antibody formulations |
| WO2020154540A1 (en) * | 2019-01-23 | 2020-07-30 | Millennium Pharmaceuticals, Inc. | Anti-cd38 antibodies |
| PE20221465A1 (es) | 2020-01-13 | 2022-09-21 | Denali Therapeutics Inc | Anticuerpos anti-trem2 y metodos para utilizarlos |
| BR112022016216A2 (pt) * | 2020-02-16 | 2023-02-28 | Aulos Bioscience Inc | Anticorpos anti-il-2 modificados |
| US20220275090A1 (en) | 2021-02-22 | 2022-09-01 | Janssen Biotech, Inc. | Combination Therapies with Anti-CD38 Antibodies and PARP or Adenosine Receptor Inhibitors |
| AU2022325383A1 (en) * | 2021-08-12 | 2024-02-15 | Shanghai Jmt-Bio Technology Co., Ltd. | GPC3-TARGETED ANTIBODY INTERFERON α FUSION PROTEIN AND USE THEREOF |
| IL312514A (en) | 2021-11-03 | 2024-07-01 | Janssen Biotech Inc | Corticosteroid reduction in treatment with anti-CD38 antibodies |
| WO2023144303A1 (en) | 2022-01-31 | 2023-08-03 | INSERM (Institut National de la Santé et de la Recherche Médicale) | Cd38 as a biomarker and biotarget in t-cell lymphomas |
| WO2023223100A1 (en) * | 2022-05-18 | 2023-11-23 | Takeda Pharmaceutical Company Limited | Anti-cd38 fusion protein formulation |
| TW202423968A (zh) * | 2022-09-29 | 2024-06-16 | 日商武田藥品工業股份有限公司 | Ｃｄ３８結合融合蛋白組合療法 |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001097844A1 (en) * | 2000-06-22 | 2001-12-27 | Idec Pharmaceuticals Corporation | Bispecific fusion protein and method of use for enhancing effector cell killing of target cells |
| CN101616933A (zh) * | 2006-10-19 | 2009-12-30 | 赛诺菲-安万特 | 用于治疗癌症的新型抗-cd38抗体 |
| WO2011154453A1 (en) * | 2010-06-09 | 2011-12-15 | Genmab A/S | Antibodies against human cd38 |
Family Cites Families (104)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB2148299B (en) | 1983-09-01 | 1988-01-06 | Hybritech Inc | Antibody compositions of therapeutic agents having an extended serum half-life |
| US4908431A (en) | 1986-01-22 | 1990-03-13 | Temple University-Of The Commonwealth System Of Higher Education | Monoclonal antibodies to human kininogen and methods of preparing same |
| US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
| JP3040121B2 (ja) | 1988-01-12 | 2000-05-08 | ジェネンテク，インコーポレイテッド | 増殖因子レセプターの機能を阻害することにより腫瘍細胞を処置する方法 |
| US5846534A (en) | 1988-02-12 | 1998-12-08 | British Technology Group Limited | Antibodies to the antigen campath-1 |
| AU4128089A (en) | 1988-09-15 | 1990-03-22 | Rorer International (Overseas) Inc. | Monoclonal antibodies specific to human epidermal growth factor receptor and therapeutic methods employing same |
| ES2052027T5 (es) | 1988-11-11 | 2005-04-16 | Medical Research Council | Clonacion de secuencias de dominio variable de inmunoglobulina. |
| US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
| US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
| US5976531A (en) | 1990-04-19 | 1999-11-02 | The Dow Chemical Company | Composite antibodies of human subgroup IV light chain capable of binding to tag-72 |
| GB9022543D0 (en) | 1990-10-17 | 1990-11-28 | Wellcome Found | Antibody production |
| US5650150A (en) | 1990-11-09 | 1997-07-22 | Gillies; Stephen D. | Recombinant antibody cytokine fusion proteins |
| US5558864A (en) | 1991-03-06 | 1996-09-24 | Merck Patent Gesellschaft Mit Beschrankter Haftung | Humanized and chimeric anti-epidermal growth factor receptor monoclonal antibodies |
| DK0628639T3 (da) | 1991-04-25 | 2000-01-24 | Chugai Pharmaceutical Co Ltd | Rekonstitueret humant antistof mod human interleukin-6-receptor |
| WO1994004679A1 (en) | 1991-06-14 | 1994-03-03 | Genentech, Inc. | Method for making humanized antibodies |
| US5565332A (en) | 1991-09-23 | 1996-10-15 | Medical Research Council | Production of chimeric antibodies - a combinatorial approach |
| US6042828A (en) | 1992-09-07 | 2000-03-28 | Kyowa Hakko Kogyo Co., Ltd. | Humanized antibodies to ganglioside GM2 |
| CA2126967A1 (en) | 1992-11-04 | 1994-05-11 | Anna M. Wu | Novel antibody construct |
| US5840299A (en) | 1994-01-25 | 1998-11-24 | Athena Neurosciences, Inc. | Humanized antibodies against leukocyte adhesion molecule VLA-4 |
| HU221001B1 (hu) | 1994-03-17 | 2002-07-29 | Merck Patent Gmbh. | Egyláncú anti-EGFR Fv-k és anti-EGFR ellenanyagok |
| DE69523857T2 (de) | 1994-09-16 | 2002-06-13 | Merck Patent Gmbh | Immunokonjugate |
| US20020164788A1 (en) * | 1994-12-02 | 2002-11-07 | The Wellcome Foundation Limited | Humanized antibodies to CD38 |
| WO1997000271A1 (en) | 1995-06-14 | 1997-01-03 | The Regents Of The University Of California | Novel high affinity human antibodies to tumor antigens |
| DE69621940T2 (de) | 1995-08-18 | 2003-01-16 | Morphosys Ag | Protein-/(poly)peptidbibliotheken |
| US5723125A (en) | 1995-12-28 | 1998-03-03 | Tanox Biosystems, Inc. | Hybrid with interferon-alpha and an immunoglobulin Fc linked through a non-immunogenic peptide |
| HUP9901562A3 (en) | 1996-05-04 | 2000-06-28 | Astrazeneca Ab | Monoclonal antibody to cea, conjugates comprising said antibody, and their therapeutic use in an adept system |
| US6417337B1 (en) | 1996-10-31 | 2002-07-09 | The Dow Chemical Company | High affinity humanized anti-CEA monoclonal antibodies |
| US6277375B1 (en) | 1997-03-03 | 2001-08-21 | Board Of Regents, The University Of Texas System | Immunoglobulin-like domains with increased half-lives |
| US6872568B1 (en) | 1997-03-17 | 2005-03-29 | Human Genome Sciences, Inc. | Death domain containing receptor 5 antibodies |
| EP1012184B1 (en) | 1997-07-14 | 2007-10-10 | Bolder Biotechnology, Inc. | Derivatives of growth hormone and related proteins |
| AUPP221098A0 (en) | 1998-03-06 | 1998-04-02 | Diatech Pty Ltd | V-like domain binding molecules |
| EP1071700B1 (en) | 1998-04-20 | 2010-02-17 | GlycArt Biotechnology AG | Glycosylation engineering of antibodies for improving antibody-dependent cellular cytotoxicity |
| CA2343094A1 (en) | 1998-10-16 | 2000-04-27 | Biogen, Inc. | Interferon-beta fusion proteins and uses |
| CA2354377C (en) | 1998-12-09 | 2007-04-10 | Tatsuji Seki | A method for manufacturing glycoproteins having human-type glycosylation |
| US7223397B1 (en) | 1999-01-07 | 2007-05-29 | Research Development Foundation | Potentiation of anti-CD38-Immunotoxin cytotoxicity |
| EP1141024B1 (en) | 1999-01-15 | 2018-08-08 | Genentech, Inc. | POLYPEPTIDE COMPRISING A VARIANT HUMAN IgG1 Fc REGION |
| JP4778617B2 (ja) | 1999-03-12 | 2011-09-21 | ジョージタウン ユニバーシティ | マトリプターゼ、セリンプロテアーゼおよびその応用 |
| US6946129B1 (en) | 1999-06-08 | 2005-09-20 | Seattle Genetics, Inc. | Recombinant anti-CD40 antibody and uses thereof |
| AU4314801A (en) | 2000-02-11 | 2001-08-20 | Lexigen Pharm Corp | Enhancing the circulating half-life of antibody-based fusion proteins |
| US7063845B2 (en) | 2000-04-28 | 2006-06-20 | Gemini Science, Inc. | Human anti-CD40 antibodies |
| US7521047B2 (en) | 2000-05-12 | 2009-04-21 | Gpc Biotech Ag | Human polypeptides causing or leading to the killing of cells including lymphoid tumor cells |
| EP2322644A1 (en) | 2000-06-28 | 2011-05-18 | GlycoFi, Inc. | Methods for producing modified glycoproteins |
| EP1174440A1 (en) | 2000-07-19 | 2002-01-23 | U-BISys B.V. | A selectively-expressed epitope on the human CD38 molecule detected by a phage display library-derived human scFv antibody fragment |
| DE60143544D1 (de) | 2000-12-12 | 2011-01-05 | Medimmune Llc | Moleküle mit längeren halbwertszeiten, zusammensetzungen und deren verwendung |
| HUP0302525A2 (hu) | 2001-01-05 | 2003-10-28 | Abgenix, Inc. | Az inzulinszerű növekedési faktor I receptor elleni ellenanyagok |
| FR2823764B1 (fr) | 2001-04-24 | 2003-12-12 | Genodyssee | Nouveaux polynucleotides et polypeptides du gene ifn alpha-17 |
| US20020193569A1 (en) | 2001-06-04 | 2002-12-19 | Idec Pharmaceuticals Corporation | Bispecific fusion protein and method of use for enhancing effector cell killing of target cells |
| DK1409544T3 (da) | 2001-07-03 | 2009-10-26 | Genentech Inc | Humane DR4-antistoffer og anvendelser deraf |
| AU2002368077B2 (en) | 2001-07-12 | 2010-03-04 | Jefferson Foote | Super humanized antibodies |
| AR035119A1 (es) | 2001-08-16 | 2004-04-14 | Lilly Co Eli | Anticuerpos humanos antagonistas anti-htnfsf13b |
| AR039067A1 (es) | 2001-11-09 | 2005-02-09 | Pfizer Prod Inc | Anticuerpos para cd40 |
| CA2471702C (en) | 2002-01-09 | 2013-03-19 | Medarex, Inc. | Human monoclonal antibodies against cd30 |
| US20040132101A1 (en) | 2002-09-27 | 2004-07-08 | Xencor | Optimized Fc variants and methods for their generation |
| US7317091B2 (en) | 2002-03-01 | 2008-01-08 | Xencor, Inc. | Optimized Fc variants |
| JP4472351B2 (ja) | 2002-03-01 | 2010-06-02 | イミューノメディクス、インコーポレイテッド | インターナライジング抗ｃｄ７４抗体およびその使用方法 |
| US7332580B2 (en) | 2002-04-05 | 2008-02-19 | The Regents Of The University Of California | Bispecific single chain Fv antibody molecules and methods of use thereof |
| US7202346B2 (en) | 2002-07-03 | 2007-04-10 | Immunogen Inc. | Antibodies to non-shed Muc1 and Muc16, and uses thereof |
| US7217797B2 (en) | 2002-10-15 | 2007-05-15 | Pdl Biopharma, Inc. | Alteration of FcRn binding affinities or serum half-lives of antibodies by mutagenesis |
| US7534427B2 (en) * | 2002-12-31 | 2009-05-19 | Immunomedics, Inc. | Immunotherapy of B cell malignancies and autoimmune diseases using unconjugated antibodies and conjugated antibodies and antibody combinations and fusion proteins |
| JP2007524351A (ja) | 2003-02-18 | 2007-08-30 | メルク パテント ゲゼルシャフト ミット ベシュレンクテル ハフトング | 改良された特性を有するインターフェロンアルファムテインの融合タンパク質 |
| US7709610B2 (en) | 2003-05-08 | 2010-05-04 | Facet Biotech Corporation | Therapeutic use of anti-CS1 antibodies |
| DE10343708A1 (de) | 2003-09-18 | 2005-05-12 | Nexpress Solutions Llc | Verfahren für das Befestigen von Toner an einem Bedruckstoff und Mikrowelleneinrichtung |
| EP1844815B1 (en) | 2003-11-04 | 2011-09-14 | Novartis Vaccines and Diagnostics, Inc. | Combination therapy comprising anti-CD20 and anti-CD40 antibodies for the treatment of B cell-related cancers |
| MXPA06008700A (es) | 2004-02-06 | 2007-01-19 | Morphosys Ag | Anticuerpos anti-cd38 humanos y usos para los mismos. |
| WO2005103083A2 (en) * | 2004-02-06 | 2005-11-03 | Morphosys Ag | Anti-cd38 human antibodies and uses therefor |
| US8034352B2 (en) | 2005-04-06 | 2011-10-11 | Ibc Pharmaceuticals, Inc. | Tetrameric cytokines with improved biological activity |
| US7273608B2 (en) | 2004-03-11 | 2007-09-25 | City Of Hope | Humanized anti-CEA T84.66 antibody and uses thereof |
| US7670595B2 (en) | 2004-06-28 | 2010-03-02 | Merck Patent Gmbh | Fc-interferon-beta fusion proteins |
| CA2601417C (en) | 2004-07-01 | 2018-10-30 | Novo Nordisk A/S | Human anti-kir antibodies |
| JP5222559B2 (ja) | 2004-10-15 | 2013-06-26 | シアトル ジェネティックス， インコーポレイテッド | 癌および免疫障害の処置および予防のための抗ｃｄ７０抗体ならびにその使用 |
| MX2007011064A (es) | 2005-03-23 | 2008-02-19 | Genmab As | Anticuerpos contra cd38 para tratamiento de mieloma multiple. |
| TW200745162A (en) | 2005-05-24 | 2007-12-16 | Morphosys Ag | Generation and profiling of fully human hucal gold-derived therapeutic antibodies specific for human CD38 |
| JP2008545409A (ja) | 2005-05-26 | 2008-12-18 | シェーリング コーポレイション | インターフェロン−ＩｇＧ融合体 |
| JP5208733B2 (ja) | 2005-06-29 | 2013-06-12 | イエダ リサーチ アンド デベロップメント カンパニー リミテッド | 組換えインターフェロンα２（ＩＦＮα２）変異体 |
| EA021669B1 (ru) | 2005-07-18 | 2015-08-31 | Амджен Инк. | Нейтрализующие антитела человека против b7rp1 |
| AU2006294663B2 (en) | 2005-09-26 | 2012-03-22 | Medarex, Inc. | Human monoclonal antibodies to CD70 |
| CN103554259B (zh) | 2005-10-12 | 2016-05-18 | 莫佛塞斯公司 | 特异性针对人CD38的完全人HuCAL GOLD-衍生治疗抗体的生成和鉴定 |
| WO2007053718A1 (en) | 2005-10-31 | 2007-05-10 | The Government Of The United States, As Represented By The Secretary Of Health And Human Services, National Institutes Of Health | Antibodies and immunotoxins that target human glycoprotein nmb |
| GB0525214D0 (en) | 2005-12-12 | 2006-01-18 | Bioinvent Int Ab | Biological materials and uses thereof |
| CN101045156B (zh) | 2006-03-29 | 2012-05-02 | 刘宏利 | 特异靶向性药物及其用途 |
| EP1878747A1 (en) | 2006-07-11 | 2008-01-16 | greenovation Biotech GmbH | Glyco-engineered antibodies |
| CA2660795C (en) * | 2006-09-18 | 2014-11-18 | Xencor, Inc. | Optimized antibodies that target hm1.24 |
| TR201910145T4 (tr) | 2006-09-26 | 2019-08-21 | Genmab As | Tümörlerin tedavi edilmesine yönelik anti-CD38 artı kortikosteroidler artı bir kortikosteroid-olmayan kemoterapötik. |
| DE102007001370A1 (de) | 2007-01-09 | 2008-07-10 | Curevac Gmbh | RNA-kodierte Antikörper |
| US11535673B2 (en) | 2007-04-05 | 2022-12-27 | President and Fellows of Harvard CoHege | Chimeric activators: quantitatively designed protein therapeutics and uses thereof |
| TW200902554A (en) | 2007-05-08 | 2009-01-16 | Genentech Inc | Cysteine engineered anti-MUC16 antibodies and antibody drug conjugates |
| WO2008145139A1 (en) | 2007-05-31 | 2008-12-04 | Genmab A/S | Fusion or linked proteins with extended half life |
| AU2008282729B2 (en) | 2007-08-01 | 2015-07-16 | Scott & White Healthcare | A fold-back diabody diphtheria toxin immunotoxin and methods of use |
| US20090076249A1 (en) | 2007-09-19 | 2009-03-19 | Michel De Weers | Antibodies against CD38 for treatment of multiple myeloma |
| BRPI0817108B8 (pt) | 2007-09-21 | 2021-05-25 | Univ California | composição compreendendo uma proteína de fusão, kit compreendendo a referida composição e uso da mesma. |
| US8092804B2 (en) | 2007-12-21 | 2012-01-10 | Medimmune Limited | Binding members for interleukin-4 receptor alpha (IL-4Rα)-173 |
| PL2238168T3 (pl) | 2007-12-26 | 2014-11-28 | Biotest Ag | Środki które mają za cel CD138 i ich zastosowania |
| EP2313435A4 (en) | 2008-07-01 | 2012-08-08 | Aveo Pharmaceuticals Inc | FIBROBLAST GROWTH FACTOR RECEPTOR 3 (FGFR3) BINDING PROTEINS |
| EP2408820A4 (en) | 2009-03-16 | 2013-01-23 | Cephalon Australia Pty Ltd | HUMANIZED ANTIBODIES WITH ANTITUMOR EFFECT |
| LT2621531T (lt) | 2010-09-27 | 2017-04-10 | Morphosys Ag | Anti-cd38 antikūnas ir lenalidomidas arba bortezomibas, skirti išsėtinės mielomos ir nhl (nehodžino limfoma) gydymui |
| PT2654790T (pt) | 2010-12-22 | 2019-05-16 | Teva Pharmaceuticals Australia Pty Ltd | Anticorpo modificado com semivida melhorada |
| JOP20210044A1 (ar) * | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | الأجسام المضادة لـ cd38 |
| KR102096224B1 (ko) * | 2011-10-28 | 2020-04-03 | 테바 파마슈티컬즈 오스트레일리아 피티와이 엘티디 | 폴리펩티드 구축물 및 이의 용도 |
| JP6416628B2 (ja) | 2012-01-20 | 2018-10-31 | ブイアイビー ブイゼットダブリュＶｉｂ Ｖｚｗ | 標的変異体αヘリックスバンドルサイトカイン |
| CN104470536A (zh) | 2012-03-03 | 2015-03-25 | 免疫基因公司 | 工程化的抗体-干扰素突变体融合分子 |
| WO2014028502A1 (en) | 2012-08-13 | 2014-02-20 | ImmunGene Inc. | Engineered antibody-interferon fusion molecules for treatment of autoimmune diseases |
| MX370377B (es) | 2013-04-29 | 2019-12-11 | Teva Pharmaceuticals Australia Pty Ltd | Anticuerpos anti-cd38 y fusiones con interferón alfa-2b atenuado. |
| UA119352C2 (uk) | 2014-05-01 | 2019-06-10 | Тева Фармасьютикалз Острейліа Пті Лтд | Комбінація леналідоміду або помалідоміду і конструкції анти-cd38 антитіло-атенуйований інтерферон альфа-2b та спосіб лікування суб'єкта, який має cd38-експресуючу пухлину |
| JP6730271B2 (ja) | 2014-10-29 | 2020-07-29 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | インターフェロンα２Ｂバリアント |
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Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2001097844A1 (en) * | 2000-06-22 | 2001-12-27 | Idec Pharmaceuticals Corporation | Bispecific fusion protein and method of use for enhancing effector cell killing of target cells |
| CN101616933A (zh) * | 2006-10-19 | 2009-12-30 | 赛诺菲-安万特 | 用于治疗癌症的新型抗-cd38抗体 |
| WO2011154453A1 (en) * | 2010-06-09 | 2011-12-15 | Genmab A/S | Antibodies against human cd38 |
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