CN107446053A - 癌症的抑制 - Google Patents

癌症的抑制 Download PDF

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CN107446053A
CN107446053A CN201710541016.7A CN201710541016A CN107446053A CN 107446053 A CN107446053 A CN 107446053A CN 201710541016 A CN201710541016 A CN 201710541016A CN 107446053 A CN107446053 A CN 107446053A
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弗雷德里克·马代克
菲尔·莱卡纳
P·马科斯
K·福斯特
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Abstract

本发明涉及用于抑制或治疗癌症的方法，特别涉及用于抑制或治疗结肠直肠癌、乳腺癌、前列腺癌和/或肺癌的一种或多种的方法。该疗法采用靶向于生长激素分泌细胞例如靶向于垂体细胞的非细胞毒性蛋白酶。当如此被递送时，所述蛋白酶被内化并抑制生长激素从所述细胞的分泌/传输。本发明还涉及用于所述方法的多肽和核酸。

Description

癌症的抑制
本申请是申请日为2009年6月11日的、发明名称为“癌症的抑制”的中国专利申请200980122092.8(PCT/GB2009/050666)的分案申请。
本发明涉及常见癌症，特别是结肠直肠癌、前列腺癌、乳腺癌和肺癌的生长、维持和进展的抑制。
结肠直肠癌在美国男性和女性两者中都是第三大常见癌症，根据世界卫生组织在2003年4月关于全球患癌率的报告，每年有超过940 000新病例被诊断并且每年全世界报道近500,000例死亡。结肠癌的总体5年存活率大约为60％，并且在美国每年有近60,000人死于该疾病。
目前采用的疗法主要根据结肠或直肠中肿瘤的位置和疾病阶段，并且可以包括a)外科手术，b)化疗，c)生物疗法或d)放射疗法。去除原发肿瘤的外科手术是主要的一线治疗。然而，外科手术的常见不良副作用包括手术出血、腿部血块以及手术过程中对邻近器官的损害。
手术选择包括：(i)肠切除，其包括切入腹部以达到受癌影响的结肠或直肠区域。外科医生去除癌及其附近的结肠或直肠的部分。然后，将结肠或直肠的两个健康末端重新缝合在一起；(ii)肝切除，其包括去除已经从结肠直肠区域扩散至肝的转移灶以及癌附近的肝部分。多达一半的肝可以被去除，只要剩余部分是健康的。破坏肝中癌细胞的两种其他方法包括放射波(射频消蚀)和热(微波凝固)，和(iii)冷冻手术(还称为冷冻疗法)，其采用液氮冷冻并破坏已经扩散至肝的结肠直肠癌。其在肝中肿瘤尺寸小时被使用。
化疗通常用作针对少数患者外科手术的辅助，通常针对肿瘤已经扩散至淋巴结、化疗对其益处已经明确的那些患者。然而，化疗副作用包括：恶心、呕吐、食欲不振、脱发、口腔溃疡、手足疹，还包括：感染风险、轻伤的出血或青肿、以及贫血相关的疲劳。化疗可以在多种情况下使用：(i)首选化疗通常在结肠直肠癌晚期并已扩散至身体其他部分时使用。这种情况下，外科手术不能清除癌，所以此时医生通常建议化疗，化疗可以收缩肿瘤结节、缓解症状并延长寿命；(ii)辅助化疗在癌已经被手术去除之后给予化疗时采用。外科手术可能不会清除所有癌，因此辅助化疗治疗通常用于杀伤可能被漏掉的任何癌细胞，例如可能已经转移或扩散至肝的细胞；和(iii)新辅助化疗可以在外科手术之前采用以收缩肿瘤，以便外科医生能够完全去除肿瘤而产生较少并发症。化疗通常与放射一起使用以使放射更有效。
生物疗法可以被指定用于患有已经扩散的癌症的人。目前疗法包括使用：(i)生物应答调节剂，其不直接破坏癌，而是触发免疫系统反应对抗肿瘤。生物应答调节剂包括细胞因子，例如干扰素和白介素。然而，该策略包括通过注射或输注的大施用剂量的使用，希望刺激免疫系统的细胞更有效地发挥作用。此外，生物应答调节剂的使用通常伴随流感样症状，包括发热、寒战、恶心和食欲不振。其他不希望的副作用包括：注射部位皮疹或肿胀、治疗导致的血压下降、和疲劳；(ii)集落刺激因子，其刺激产生骨髓细胞，例如红细胞和白细胞和血小板。因此，集落刺激因子不直接影响肿瘤，而是在癌症治疗过程中帮助支持免疫系统。但遗憾的是，集落刺激因子的使用伴随不希望的副作用，例如骨痛、疲劳、发热和食欲不振；和(iii)肿瘤疫苗，其促使免疫系统识别癌细胞。所述疫苗通常在癌症发作之后采用，因此是抑制性而非预防性的。效力差，并且肿瘤疫苗的使用伴随肌肉疼痛和低热。
结肠直肠癌治疗的主要困难在于20-25％患者在最初诊断时具有临床可检测的肝转移，并且另外有40-50％患者在初次手术之后三年内发展肝转移，通常转移性疾病首先在肝中发展。
除了非黑素瘤皮肤癌之外，乳腺癌是女性中最常见的癌症类型。在2007年，估计美国女性中有近180,000例侵袭性乳腺癌新病例被诊断。女性发生侵袭性乳腺癌的终生风险是约1/8(13％)。
目前疗法包括：外科手术、放射疗法、化疗、激素疗法和生物疗法。选择一种疗法而不选择另一种疗法涉及如下考虑：肿瘤尺寸和位置，组织学因素(例如淋巴侵袭和组织学亚型确定)，疾病阶段或程度，以及患者年龄和健康状况。
外科手术选择包括乳房切除术和肿块切除术(还称为保乳疗法或乳房部分切除术)，去除或不去除淋巴结。不幸的是，经历乳房切除术的患者通常遭受下述一种或多种：伤口感染和脓肿、皮瓣坏死、胸壁感觉异常、乳房假体综合征、术后疼痛综合征、血清肿或淋巴水肿。类似地，肿块切除术伴随的并发症包括：腋静脉损伤或血栓形成、血清肿形成、淋巴水肿、肩运动受损、臂丛损伤和胸壁痛。
放射疗法伴随如下并发症：乳房软组织坏死、长期乳房水肿、肋骨骨折、肩活动性降低、具有感觉异常和臂痛的臂丛病变、淋巴水肿、血管肉瘤、肺癌、冠状动脉疾病和症状性肺炎。
然而，目前的化疗选择伴随不希望的副作用，例如：恶心、脱发、绝经期提前、热潮红、疲劳和暂时降低的血球计数。此外，更严重的副作用包括：肝毒性、出血性膀胱炎、闭经、小脑共济失调、心肌功能不全、外周神经病变、骨髓抑制、神经毒性、秃顶和胸膜渗漏。
迄今，激素疗法集中于TamoxifenTM的使用和/或芳香酶抑制剂例如ArimidexTM、AromasinTM和FemaraTM的使用。这些治疗分子通过抑制激素特别是雌激素活性而起作用，并因此抑制可在乳腺癌手术后保留的乳腺癌细胞的生长。但不幸的是，激素疗法伴随不希望的副作用，例如热潮红和阴道干燥。特别是已经显示TamoxifenTM治疗增加子宫内膜癌风险、诱导围绝经期症状并增加发展白内障的风险。
迄今，生物疗法集中于HerceptinTM的使用。然而，该治疗分子的使用伴随如下不良作用：心脏毒性、发热、寒战、恶心、呕吐，并且特别是在初次输注之后可发生疼痛。
前列腺癌是死于癌症的美国男性中第二大死亡原因，并且是美国男性中诊断的最常见癌症。在美国，估计10个男性中有一个将在其生命中发展前列腺癌。
与其他癌症类型一样，可用的治疗根据多种因素，例如癌症级别和阶段，患者年龄和健康状况。目前疗法包括：(i)基于PSA血液测试的观察等待，PSA血液测试被定期进行以检查患者病症还未恶化。该方法被推荐用于影响老年男性的小的、缓慢生长的、非侵略性癌症，其中所述癌症不影响他们的预期寿命；(ii)前列腺切除术(即，去除前列腺)，但是其伴随如下副作用：膀胱控制问题、漏尿、阳痿和吻合口狭窄；(iii)放射疗法，例如使用高功率X射线的外部束放射疗法(EBRT)，但是该疗法伴随直肠问题、持续出血和直肠溃疡。可选地，可以使用直接植入前列腺的放射性粒源植入体(radioactive seed implant)。该疗法还称为短距离放射疗法，并且递送比通常用外部束所实现的更低的放射剂量(在较长时段内)。不幸的是，该类型的疗法伴随诸如缓慢且疼痛的排尿和阳痿等并发症；(iv)激素疗法，其被设计为预防雄性激素刺激癌细胞生长。这通常是通过化学抑制雄性激素分泌或通过外科手术方式(睾丸去除)来实现。不幸的是，这些疗法伴随如下副作用：乳房增大、性欲降低、阳痿、热潮红、体重增加和肌肉和骨质量减少。此外，已经显示一些激素疗法药物导致恶心、腹泻、疲劳和肝损伤；(v)化疗–采用与上文结肠直肠癌、乳腺癌或前列腺癌上下文中描述的相同类型的药物；和(vi)冷冻疗法，其通过冷冻受影响组织而破坏癌细胞。遗憾的是，该疗法受到限制，因为难以监测冷冻过程的程度，经常导致对膀胱周围组织的损伤和长期并发症(例如，对直肠或控制排尿的肌肉的损伤)。
肺癌是世界上男性和女性中癌症相关死亡的首要原因。世界范围内，肺癌依然是最常见的恶性疾病，估计每年有104万新病例，这占被诊断的癌症新病例的12.8％。肺癌导致世界上每年921,000例死亡，占癌症相关死亡的近18％。
目前肺癌疗法包括单独或组合的外科手术、放射疗法和化疗。当采用所述疗法时，医生考虑：肺癌类型(小细胞或非小细胞)，肿瘤尺寸和位置，肿瘤阶段(肺之外是否存在转移)，和患者的健康状况。
对于非小细胞肺癌(NSCLC)，目前可用的治疗包括：(i)化疗–不幸的是，NSCLC对化疗仅中度敏感。单剂疗法应答率大约为15％，较新的药剂(例如GemcitabineTM、PaclitaxelTM、DocetaxelTM、VinorelbineTM)具有略高的应答率(20-25％)。此外，化疗伴随如下并发症：血细胞数目减少、恶心、呕吐、腹泻、口疮和口腔溃疡、脱发和疲劳；(ii)生物疗法–最近的研究努力重点集中于鉴定分子靶标并利用该认识来发展分子靶向疗法。虽然几种分钟靶向疗法目前被开发并在NSCLC中测试，但这些疗法伴随不希望的副作用，包括：流感样症状，例如：寒战、发热、肌肉疼痛、疲劳、食欲不振、恶心、呕吐和腹泻；(iii)放射疗法。该类型疗法通常用作外科手术的辅助，或者在因为有限的肺储备或存在合并症而不能手术切除时单独使用。在早期NSCLC中，单独的放射疗法仅伴随12-16％的5年后存活率。遗憾的是，并发症是常见的，并且包括：恶心、疲劳、皮肤反应、脱发、持续咳嗽、咽喉干燥或疼痛、以及吞咽困难；(iv)联合化疗放疗–最近研究已经显示，当用共存(而非顺序)的基于铂的化疗和放射疗法治疗时，具有不可切切除的III期疾病的患者中有限的存活。然而，与上述癌症类型一样，化疗和放疗的使用具有许多不希望的副作用；(v)外科手术–这通常在肿瘤处于早期和/或肿瘤还未扩散时采用。实例包括：楔形切除术，其包括去除三角形的组织薄片。楔形切除术被用来去除肿瘤及其周围的小量正常组织。当处理较大量组织时，称为分段切除；叶切除术，其包括肺的整个叶(段)的去除；和肺切除术，其包括一个完整肺的去除。这些治疗介入之后遭遇的副作用包括：疼痛、感染，还包括：肺炎、出血、血块和其他感染。此外，手术期间的死亡率：肺切除术是6％，叶切除术是3％，而肺段切除术是1％。
对于小细胞肺癌(SCLC)，目前可用的治疗包括：(i)化疗–单剂化疗显示范围从17％至50％的应答率。联合化疗具有良好的应答率和存活率，但是主要副作用包括：骨髓抑制、肾毒性、肿瘤溶解综合征(特征为：高尿酸血症、高磷酸盐血症、低血钙症、脱水和血钾过多症)、脊髓受压和低血钠；(ii)放射疗法–该疗法仅用于减轻症状，并且患者一定会复发；(iii)外科手术–大部分SCLC患者非手术治疗。例外是具有局限于肺而没有涉及任何淋巴结的非常早期疾病的相对小数目的患者(<5％)。此类患者通常在最初诊断程序时经历肺肿瘤切除术。然而，即使对于这些患者，单独的外科手术被认为不是治愈性的。
具有复发型SCLC的患者具有极差的预后，大约65-70％的SCLC患者在展示时具有弥散的疾病。扩散阶段的SCLC目前是不可治愈的，并且具有扩散性疾病的患者的中值存活时间小于1年。即使呈现局部疾病(即，局限期)的患者，其中值存活时间小于2年。SCLC的5年存活率小于20％。
就上述讨论的目前可用的全部疗法(对于讨论的癌症类型的每一个：-结肠直肠癌、乳腺癌、前列腺癌和肺癌)而言，存在另一个问题，即，肿瘤溶解综合征(TLS)。TLS是非常严重且有时威胁生命的癌症疗法并发症。其可以被定义为自发的或治疗相关的肿瘤坏死或爆发性细胞凋亡导致的代谢异常集合。TLS患者中观察到的代谢异常包括：血钾过多症、高尿酸血症和高磷酸盐血症与继发性低血钙症；并且可以导致急性肾衰竭(ARF)。
癌症(尤其是结肠直肠癌、乳腺癌、前列腺癌和肺癌)继续成为全球范围内动物保健的主要问题。因此，本领域存在对解决上述问题的一个或多个的替代和/或改良的癌症治疗剂和疗法的需求。
本发明通过提供新一类非细胞毒性抗癌剂而解决了所述问题的一个或多个。
更具体说，本发明第一方面提供了用于治疗癌症的多肽，所述多肽包括：
a.非细胞毒性蛋白酶，所述蛋白酶能够在生长激素分泌细胞中切割细胞外融合器(exocytic fusion apparatus)的蛋白；
b.靶向部分(TM)，其能够与生长激素分泌细胞上的结合位点结合，所述结合位点能够经历胞吞作用以被并入所述生长激素分泌细胞的内体；和
c.易位结构域，其能够从所述内体内、跨内体膜和进入所述生长激素分泌细胞的胞质溶胶中易位所述蛋白酶。
使用中，本发明多肽结合生长激素分泌细胞。此后，易位组分导致蛋白酶组分转运入生长激素分泌细胞的胞质溶胶。最后，一旦在内部，蛋白酶抑制生长激素分泌细胞的细胞外融合过程。因此，通过失活生长激素分泌细胞的细胞外融合器，本发明多肽抑制生长激素从其释放/分泌。
本发明多肽的‘生物活性’组分由非细胞毒性蛋白酶提供。这一独特的蛋白酶组通过蛋白酶切割称为SNARE蛋白的细胞内转运蛋白(例如，SNAP-25、VAMP或突触融合蛋白)而发挥作用–参见Gerald K(2002)“Cell and Molecular Biology(细胞分子生物学)”(第四版)John Wiley&Sons,Inc。首字母缩写SNARE源自术语可溶性NSF附着受体(Soluble NSFAttachment Receptor)，其中NSF指N-乙基马来酰亚胺-敏感因子(N-ethylmaleimide-Sensitive Factor)。SNARE蛋白是细胞内囊泡形成以及由此通过囊泡转运从细胞分泌分子所必不可少的。因此，一旦被递送至预期靶细胞，则非细胞毒性蛋白酶能够抑制靶细胞的细胞分泌。
本发明多肽结合的主要靶细胞是分泌生长激素正常的、非病态的、非癌细胞。然而，这些细胞不同于根据本发明治疗的最终的‘下游’癌细胞。
本发明提供能够(并用于)减少/最小化生长激素和/或胰岛素样生长因子(IGF-1)的全身或血清水平的多肽。还提供了用于减少/最小化肿瘤溶解综合征(TLS)的多肽。
本发明多肽特别适合用于治疗以下的一种或多种：结肠直肠癌、乳腺癌、前列腺癌和/或肺癌(例如SCLC或NSCLC)；包括它们的转移、癌前状态及其症状。就这方面而言，‘治疗’包括减少、预防或消除局部、区域或体循环中的癌细胞及其扩散。
因此，在本发明的一个相关方面，提供了用于治疗患者癌症的方法，所述方法包括向患者施用治疗有效量的本发明多肽。本发明还提供了用于减少患者中生长激素和/或IGF-1水平(优选全身和/或血清水平)的方法，所述方法包括向患者施用治疗有效量的本发明多肽。作为实例，在一个实施方案中，本发明允许保持生长激素基础水平在约10ng/ml、优选小于6ng/ml、更优选小于4或5ng/ml的阈值。在正常人中，每日生长激素水平可以在睡眠开始后约1小时达到峰值，水平约35ng/ml。就这一点而言，在一个实施方案中，本发明允许所述峰值被控制在约25ng/ml、优选小于20ng/ml、更优选小于15ng/ml的阈值。还提供了用于减少/最小化肿瘤溶解综合征(TLS)的方法。
不希望受任何理论束缚，本发明人相信升高的生长激素全身水平导致全身IGF-1的水平变得升高，并且后者导致增加的IGF-1R活化和癌基因活化的伴随增加，这转而导致增加的细胞增殖和肿瘤形成/生长。
在本发明多肽施用之后，观察到生长激素(例如，人GH)从垂体前部的分泌下降。类似地，观察到循环IGF-1水平的水平降低。GH/IGF-1水平的所述降低与肿瘤收缩相关。因此，本发明多肽的使用通过去除主要的对抗作用生物途径之一而提供了用于癌症治疗的有利环境。
施用之后，癌症的区域和远端扩散被减少或消除。就这方面而言，不希望受任何理论束缚，本发明人相信，转移的扩散被本发明多肽所抑制，本发明多肽降低了IGF-1的循环浓度。
本发明的一个优点在于，癌症治疗之后，垂体功能恢复正常。换言之，本发明提供了对垂体具有最小治疗后作用的短效疗法。因此，与目前垂体切除疗法不同，本发明不需要为防止最初癌症治疗导致的并发症的复杂且令人不悦的治疗后(通常是长期的)方案，所述并发症例如：骨质疏松、短肠综合征、可导致阿尔茨海默病的记忆丧失、关节炎、背痛、纤维肌痛和慢性疲劳。
本发明多肽的生物活性组分是非细胞毒性蛋白酶。非细胞毒性蛋白酶是不杀伤细胞的独立的一类分子；相反，它们通过抑制除了蛋白合成外的细胞过程而发挥作用。非细胞毒性蛋白酶作为较大毒性分子的部分由多种植物和多种微生物产生，所述微生物例如梭状芽孢杆菌(Clostridium sp.)和奈瑟菌(Neisseria sp.)。
梭菌神经毒素代表主要的一组非细胞毒性毒素分子，并且包括通过二硫键连接在一起的两条多肽链。两条链被称为重链(H-链)和轻链(L-链)，重链分子量为大约100kDa，轻链分子量为大约50kDa。L链具有蛋白酶功能并表现出对参与细胞外过程的囊泡和/或质膜相关(SNARE)蛋白(例如，小突触泡蛋白、突触融合蛋白或SNAP-25)高底物特异性。这些底物是神经分泌器的重要组分。
主要来自淋球菌(N.gonorrhoeae)种的奈瑟菌和主要来自肺炎链球菌(S.pneumoniae)种的链球菌产生功能上类似的非细胞毒性毒素分子。此类非细胞毒性蛋白酶的实例是IgA蛋白酶(参见WO99/58571，其在此通过引用整体并入)。
因此，本发明的非细胞毒性蛋白酶优选是梭菌神经毒素蛋白酶或IgA蛋白酶。
现在讨论本发明的靶向部分(TM)组分，该组分使本发明多肽结合生长激素分泌细胞、优选结合垂体细胞和/或结合外垂体细胞(extrapituitary cell)。在一个实施方案中，TM结合垂体腺的前部区域，例如结合促生长素细胞和/或腺垂体细胞。
适合的TM包括：生长激素分泌细胞受体的配体，例如细胞因子、生长因子、神经肽、凝集素和抗体–该术语包括单克隆抗体和抗体片段，例如Fab、F(ab)'2、Fv、ScFv等。
本发明TM结合生长激素分泌细胞例如垂体细胞上的受体。作为实例，TM可以结合瘦蛋白(OB)受体及其同种型、生长素释放肽受体、促生长素抑制素(sst)受体(例如sst1、sst2、sst3、sst4和sst5及其剪接变体)、胰岛素生长因子(IGF)受体(例如IGF-1)、erbB受体(例如erbB1、erbB2、erbB3和erbB4及其剪接变体)、VIP-胰高血糖素-GRF-促胰液素超家族受体(包括其剪接变体)例如垂体腺苷酸环化酶活化肽(PACAP)受体(例如PAC、VPAC1和/或VPAC2)、食欲肽(OX)受体和剪接变体(例如OX1和/或OX2)、白介素(IL)受体(例如IL-1、IL-2、IL-6和IL-10受体)、神经生长因子(NTR)受体(例如TrkA(NTR)和p75(NTR))、血管内皮生长因子(VEGF)受体(例如VEGFR1、VEGFR2和VEGFR3)、铃蟾肽受体(例如BRS-1、BRS-2或BRS-3)、硬骨鱼紧张肽(urotensin)受体、黑色素浓缩激素受体1、促乳素释放激素受体、KiSS-1受体、促肾上腺皮质素释放因子受体1和生长激素释放激素(GHRH)受体。
在一个实施方案中，本发明TM结合瘦蛋白受体。此类TM的适合实例包括：瘦蛋白肽，例如全长瘦蛋白肽(例如瘦蛋白167)及其截短物或肽类似物，例如瘦蛋白22-167、瘦蛋白70-95和瘦蛋白116-122。
在另一个实施方案中，本发明的TM结合生长素释放肽受体。这方面适合的TM的实例包括：生长素释放肽，例如全长生长素释放肽(例如生长素释放肽117)及其截短物或肽类似物，例如生长素释放肽24-117和生长素释放肽52-117；[Trp3,Arg5]-生长素释放肽(1-5)、des-Gln-生长素释放肽、皮质抑素(cortistatin)-8、His-D-Trp-Ala-Trp-D-Phe-Lys-NH2、生长激素释放肽(例如GHRP-6)或海沙瑞林(hexarelin)。
在一个实施方案中，本发明的TM结合促生长素抑制素(SST)受体。作为实例，适合的TM包括：SST肽和皮质抑素(CST)-肽及其肽类似物，例如D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2(BIM 23052)、D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-D-Nal-NH2(BIM 23056)或c[Cys-Phe-Phe-D-Trp-Lys-Thr-Phe-Cys]-NH2(BIM-23268)。其他实例包括SST肽SST-14和SST-28；以及肽和肽类似物，例如奥曲肽、兰乐肽、BIM23027、伐普肽、司格列肽和SOM230。这些TM是用于结合SST受体、特别是sst1、sst2、sst3、sst4和sst5受体的优选TM。
在一个实施方案中，本发明的TM结合胰岛素样生长因子(IGF)受体。适合的实例包括例如IGF-1肽和IGF-2肽。
在一个实施方案中，本发明的TM结合VIP-胰高血糖素-GRF-促胰液素超家族受体，例如结合PAC(例如PAC1)或结合VPAC(例如VPAC-1或VPAC-2)受体。此类TM的适合实例包括垂体腺苷酸环化酶活化肽(PACAP)、血管活性肠肽(VIP)及其截短物和肽类似物。
在一个实施方案中，TM是VIP肽，包括VIP-1和VIP-2肽，例如VIP(1-28)或其截短物或肽类似物。这些TM显示与VPAC-1的选择性结合。可选地，可以采用显示与VPAC2选择性结合的TM，例如mROM(参见Yu等,Peptides 27(6)p1359-66(2006)，其在此通过引用并入)。在另一个实施方案中，TM可以是PACAP肽，例如PACAP(1-38)或PACAP(1-27)或其截短物或肽类似物。这些TM是结合PAC(例如PAC-1)受体的优选TM。
在另一个实施方案中，本发明的TM结合食欲肽受体(例如OX1或OX2受体)。适合的TM的实例包括：全长食欲肽-A肽及其截短物或肽类似物，和食欲肽-B肽及其截短物或肽类似物。
在一个实施方案中，本发明的TM结合白介素受体。适合的TM的实例包括：IL-1肽(例如IL-1α、IL-β、IL-18肽)及其截短物或肽类似物、IL-2肽(例如IL-2、IL-3、IL-12、IL-23肽)及其截短物或肽类似物、和IL-17肽(例如11-17A、IL-17C肽)及其截短物或肽类似物。
在另一个实施方案中，本发明的TM结合NGF受体。适合的TM的实例包括全长NGF及其截短物或肽类似物。
在一个实施方案中，本发明的TM结合血管活性表皮生长因子(VEGF)受体。适合的TM的实例包括：VEGF肽(例如VEGF-A、VEGF-B、VEGF-C、VEGF-D或VEGF-E及相关的剪接变体)及其截短物或肽类似物，和胎盘生长因子(PIGF)及其截短物或肽类似物。
在另一个实施方案中，本发明的TM结合ErbB受体。作为实例，TM选自EGF肽、转化生长因子-α(TGF-α)肽、EGF和TGF-α嵌合体、双调蛋白肽、β细胞调节素(betacellulin)肽、epigen肽、表皮调节素(epiregulin)肽、肝素结合EGF(HB-EGF)肽、神经调节蛋白(NRG)肽，例如NRG1α、NRG1β、NRG2α、NRG2β、NRG3、NRG4和神经调节蛋白剪接变体、tomoregulin 1和2肽、神经蛋白聚糖-C肽、lin-3肽、vein肽、gurken肽、spitz肽或keren肽；及其截短物和肽类似物。存在4类ErbB受体(称为ErbB1、erbB2、erbB3和erbB4)，其还被称为HER受体。存在这些受体的许多变体，其产生自全长受体的可变剪接和/或切割(例如EGFR v1翻译起始在aa543；EGFR vII缺失aa521-603；EGFR vIII缺失aa 6-273；EGFRvIII/Δ12-13缺失aa 6-273和409-520；EGFR vIV缺失aa 959-1030；EGFR vV截短在残基958；EGFR TDM/2-7串联重复6-273；EGFR TDM/18-25串联重复664-1030；EGFR-TDM/18-26串联重复664-1014)。此外，存在四种ErbB4受体同种型，称为erbB4JM-a、erbB4JM-b、erbB4CYT-1和erbB4CYT-1。
优选的TM结合ErbB受体(例如ErbB1、ErbB2、ErbB3、ErbB4)及其剪接变体，特别是ErbB1受体。ErbB TM还可以包括含有EGF基序的蛋白，在六半胱氨酸EGF-模块中的第四个半胱氨酸与第五个半胱氨酸之间具有剪接位点，其中所述模块紧邻潜在配体的跨膜区。例如，感光细胞间(interphotoreceptor)基质蛋白聚糖-2(IMP-2)、跨膜肽酶(MEP)1α、MEP1β、粘蛋白(MUC)3、MUC4、MUC12和MUC17，以及具有T结支架的蛋白，例如马铃薯羧肽酶抑制剂，和ErbB受体的抗体，例如西妥昔单抗、ABX-EGF、曲妥单抗或EMD72000。其他实例包括不同ErbB配体的交换结构域(环序列和/或连接氨基酸)产生的嵌合体，例如其中B-环序列已经被昆虫(果蝇)ErbB配体中存在的B-环序列替代的哺乳动物erbB受体配体、其中EGF的C-环序列已经被TGFα(44-50)的C-环序列替代的ErbB配体、其中一个或多个结构域已经被TGFα中相应序列替代而产生EGF/TGFα嵌合体(例如E3T、T3E、E4T、T4E、T3E4T、T6E和E3T4E)的EGF配体，和其中N-末端TGFα序列(WSHFND)或神经调节蛋白序列(SHLVK)已经用于替代第一个半胱氨酸残基C末端的N-末端EGF序列(NSDSE)的EGF嵌合体、T1E和Biregulin。而其他嵌合体包括其中结构域已经被另一个蛋白的EGF样结构域代替的EGF，所述另一蛋白例如血液凝固蛋白、神经发育蛋白或细胞粘附蛋白(例如Notch 3、Delta 1、EMR1、F4/80、EMR3和EMR4受体)。
在进一步实施方案中，本发明的TM结合黑色素浓缩激素受体1。在这方面适合的TM的实例包括：黑色素浓缩激素(MCH)肽，例如全长MCH及其截短物和类似物。
在另一个实施方案中，本发明的TM结合促乳素释放激素受体。在这方面适合的TM的实例包括促乳素释放肽及其截短物和类似物。
在进一步实施方案中，本发明的TM结合KiSS-1受体。在这方面适合的TM的实例包括Kisspeptin-10、Kisspeptin-54肽及其截短物和类似物。
在另一个实施方案中，本发明的TM结合促肾上腺皮质素释放因子受体1。在这方面适合的TM的实例包括促肾上腺皮质素-释放激素、尿皮质素(urocortin)1和尿皮质素2，包括其截短物和类似物。
在另一个实施方案中，本发明的TM结合生长激素释放激素(GHRH)受体。GHRH还被称为生长激素释放因子(GRF或GHRF)或somatocrinin。本发明的适合的TM实例包括全长GHRH(1-44)肽及其截短物或肽类似物，例如GHRH(1-29)；GHRH(1-37)；hGHRH(1-40)-OH；[MeTyr1，Ala15，22，Nle27]-hGHRH(1-29)-NH2；[MeTyr1，Ala8，9，15，22，28，Nle 27]-hGHRH(1-29)-NH2；cyclo(25-29)[MeTyr1，Ala15，DAsp25，Nle27，Orn29+++]-hGHRH(1-29)-NH2；(D-Tyr1)-GHRH(1-29)-NH2；(D-Ala2)-GHRH(1-29)-NH2；(D-Asp3)-GHRH(1-29)-NH2(D-Ala4)-GHRH(1-29)-NH2；(D-Thr7)-GHRH(1-29)-NH2；(D-Asn8)-GHRH(1-29)-NH2；(D-Ser9)-GHRH(1-29)-NH2；(D-Tyr10)-GHRH(1-29)-NH2；(Phe4)-GHRH(1-29)-NH2；(pCI-Phe6)-GHRH(1-29)-NH2；(N-Ac-Tyr1)-GHRH(1-29)-NH2；(N-Ac-Tyr1，D-Ala2)-GHRH(1-29)-NH2；(N-Ac-D-Tyr1，D-Ala2)-GHRH(1-29)-NH2；(N-Ac-D-Tyr1，D-Ala 2，D-Asp3)-GHRH(1-29)-NH2；(D-Ala2，NLeu27)-GHRH(1-29)-NH2；(His1，D-Ala2，NLeu27)-GHRH(1-29)-NH2；(N-Ac-His1，D-Ala2，N-Leu27)-GHRH(1-29)-NH2；(His1，D-Ala 2，D-Ala 4，Nleu27)-GHRH(1-29)-NH2；(D-Ala2，D-Asp3，D-Asn8，NLeu27)-GHRH(1-29)-NH2；(D-Asp3，D-Asn8，NLeu27)-GHRH(1-29)-NH2；[His1，NLeu27]-hGHRH(1-29)-NH2；[NLeu27]-hGHRH(1-29)-NH2；H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-Gln-Gln-Gly-Glu-Ser-Asn-Gln-Glu-Arg-Gly-Ala-Arg-Ala-Arg-Leu-NH2；H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2；H-Tyr-D-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Ser-Arg-NH2；H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Ile-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Gly-Ala-Lys-Val-Arg-Leu-NH2；H-Tyr-Ala-Asp-Ala-Ile-Phe-Thr-Asn-Ser-Tyr-Arg-Lys-Val-Leu-Gly-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Met-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Gly-Ala-Lys-Val-Arg-Leu-NH2；His-Val-Asp-Ala-Ile-Phe-Thr-GIn-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Asn-Arg；和His-Val-Asp-Ala-Ile-Phe-Thr-Gln-Ser-Tyr-Arg-Lys-Val-Leu-Ala-Gln-Leu-Ser-Ala-Arg-Lys-Leu-Leu-Gln-Asp-Ile-Leu-Asn-Arg-Gln-Gln-Gly-Glu-Arg-Asn-Gln-Glu-Gln-Gly-Ala.
在进一步实施方案中，TM结合铃蟾肽受体(例如BRS-1、BRS-2或BRS-3)。用于本发明的结合铃蟾肽受体的TM包括：铃蟾肽–最初从蛙皮肤分离的14氨基酸肽(pGlu-Gln-Arg-Leu-Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2)；和哺乳动物中两个已知的同系物，即神经调节肽B和促胃液素释放肽(GRP)，例如猪GRP-Ala-Pro-Val-Ser-Val-Gly-Gly-Gly-Thr-Val-Leu-Ala-Lys-Met-Tyr-Pro-Arg-Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Mel-NH2，和人GRP-Val-Pro-Leu-Pro-Ala-Gly-Gly-Gly-Thr-Val-Leu-Thr-Lys-Met-Tyr-Pro-Arg-Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2。额外的TM包括相应的铃蟾肽、神经调节肽B和GRP截短物及其肽类似物。
在另一个实施方案中，本发明的TM结合硬骨鱼紧张肽受体。在这方面适合的TM包括硬骨鱼紧张肽及其截短物和肽类似物，例如环状神经肽硬骨鱼紧张肽-II(U-II)。U-II的C末端环区域在不同物种中是强烈保守的，并且包括六个氨基酸残基(-Cys Ple-Trp-Lys-Tyr-Cys-)，其结构类似于促生长素抑制素-14的中央区域(-Phe-Trp-Lys-Thr-)。适用于本发明的硬骨鱼紧张肽包括U-II前体肽，例如前原-硬骨鱼紧张肽-II(包括其两个人124和139同种型)，及其截短物和类似物，例如十一残基成熟肽形式。
根据本发明的第二个方面，提供了物质组合物，即，包括以下的多肽：
a.非细胞毒性蛋白酶，所述蛋白酶能够在生长激素分泌细胞中切割细胞外融合器的蛋白；
b.靶向部分(TM)，其能够与生长激素分泌细胞上的结合位点结合，所述结合位点能够经历胞吞作用以被并入所述生长激素分泌细胞的内体；和
d.易位结构域，其能够从所述内体内易位、跨内体膜和进入所述生长激素分泌细胞的胞质溶胶中易位所述蛋白酶。
本发明第一方面的所有特征等同应用于上述第二方面。
在本发明第一方面和/或第二方面的优选实施方案中，TM具有人肽氨基酸序列。因此，优选的TM是例如人GHRH肽、人CST肽或人SST肽。
多肽制备
本发明多肽包括3个主要组分：‘生物活性’(即，非细胞毒性蛋白酶)；TM；和易位结构域。与制备此类融合蛋白相关的通用技术通常被称为再靶向毒素技术。作为示例，我们参考：WO94/21300；WO96/33273；WO98/07864；WO00/10598；WO01/21213；WO06/059093；WO00/62814；WO00/04926；WO93/15766；WO00/61192；和WO99/58571。所有这些出版物在此通过引用并入。
更具体说，本发明TM组分可以与本发明的蛋白酶组分或易位组分融合。所述融合优选通过共价键，例如直接共价键或通过间隔分子/接头分子。蛋白酶组分和易位组分优选通过共价键连接在一起，所述共价键例如直接共价键或通过间隔分子/接头分子。适合的间隔分子/接头分子是本领域公知的，并且通常包括基于氨基酸的序列，长度为5至40、优选10至30个氨基酸残基。
使用中，多肽具有双链构象，其中蛋白酶组分和易位组分优选通过二硫键连接在一起。
本发明多肽可通过技术人员公知的常规化学轭合技术来制备。作为实例，参考Hermanson,GT.(1996),Bioconjugate techniques(生物轭合技术),Academic Press,和Wong,S.S.(1991),Chemistry of protein conjugation and cross-linking(蛋白轭合和交联的化学),CRC Press,Nagy等,PNAS 95第1794-99页(1998)。使合成TM与本发明多肽连接的更详细方法提供于例如EP0257742。上述轭合出版物在此通过引用并入。
可选地，所述多肽可通过单个多肽融合蛋白的重组制备来制备(参见例如WO98/07864)。该技术基于天然梭菌神经毒素(即，全毒素)被制备的体内细菌机制，并得到具有下述‘简化’结构排列的融合蛋白：
NH2-[蛋白酶组分]-[易位组分]-[TM]-COOH
根据WO98/07864，TM被置于融合蛋白C末端。然后融合蛋白通过蛋白酶处理而被活化，所述蛋白酶切割蛋白酶组分和易位组分之间的位点。由此产生双链蛋白，包括作为与另一单多肽链共价连接(通过二硫键)的单多肽链的蛋白酶组分，所述另一单多肽链含有易位组分和TM。
可选地，根据WO06/059093，融合蛋白的TM组分位于线性融合蛋白序列中间，在蛋白酶切割位点和易位组分之间。这确保TM与易位结构域连接(即，如天然梭菌全毒素所发生的)，但是在这种情况下，两个组分的顺序与天然全毒素相反。蛋白酶切割位点的随后切割暴露TM的N末端部分并提供双链多肽融合蛋白。
上述蛋白酶切割序列可以通过常规方式以DNA水平被引入(和/或去除任何固有的切割序列)，例如通过定点诱变。可以人工或在计算机软件(例如DNASTAR,Inc.的MapDraw程序)辅助下进行筛选以确认切割序列的存在。虽然可以采用任何蛋白酶切割位点(即，梭菌的或非梭菌的)，但下述是优选的：
其他蛋白酶切割位点包括被非细胞毒性蛋白酶，例如被梭菌神经毒素切割的识别序列。这些包括被非细胞毒性蛋白酶例如梭菌神经毒素切割的SNARE(例如SNAP-25、突触融合蛋白、VAMP)蛋白识别序列。具体实例提供于US2007/0166332，其在此通过引用整体并入。
术语蛋白酶切割位点还包括内蛋白，其是自切割序列。自剪接反应是可控的，例如通过改变存在的还原剂的浓度。上述‘活化’切割位点可以被用作‘破坏性’切割位点(下文讨论)，将要并入本发明多肽的切割位点。
在优选实施方案中，本发明融合蛋白可以包括一个或多个位于N末端和/或C末端的纯化标签。虽然可以采用任何纯化标签，但下述是优选的：
His-标签(例如6×组氨酸)，优选作为C-末端和/或N-末端标签
MBP-标签(麦芽糖结合蛋白)，优选作为N-末端标签
GST-标签(谷胱甘肽-S-转移酶)，优选作为N-末端标签
His-MBP-标签，优选作为N-末端标签
GST-MBP-标签，优选作为N-末端标签
硫氧还蛋白-标签，优选作为N-末端标签
CBD-标签(壳多糖结合结构域)，优选作为N-末端标签。
融合蛋白中可以包括一个或多个肽间隔分子/接头分子。例如，肽间隔物可以在纯化标签与融合蛋白分子其余部分之间使用。
因此，本发明第三方面提供了编码上述多肽(即，本发明第二方面)的核酸(例如DNA)序列。
所述核酸可以包括在载体形式中，例如质粒中，其可以任选包括复制起点、核酸整合位点、启动子、终止子和核糖体结合位点的一个或多个。
本发明还包括用于在宿主细胞特别是大肠杆菌中或通过杆状病毒表达系统表达所述核酸序列(即，本发明第三方面)的方法。
本发明还包括用于活化本发明多肽的方法，所述方法包括使所述多肽与蛋白酶接触，所述蛋白酶在位于非细胞毒性蛋白酶组分和易位组分之间的识别位点(切割位点)切割所述多肽，从而使所述多肽转化为双链多肽，其中非细胞毒性蛋白酶组分和易位组分通过二硫键连接在一起。在优选实施方案中，识别位点对于天然存在的梭菌神经毒素和/或天然存在的IgA蛋白酶不是天然的。
本发明多肽可被进一步修饰以减少或预防与分散至非靶向区域相关的不想要的副作用。根据该实施方案，所述多肽包括破坏性切割位点。所述破坏性切割位点不同于‘活化’位点(即，双链形成)，并且可被第二蛋白酶切割并且不可被非细胞毒性蛋白酶切割。而且，当通过第二蛋白酶在破坏性切割位点如此切割时，所述多肽效价降低(例如对预期靶细胞的结合能力降低，易位活性降低和/或非细胞毒性蛋白酶活性降低)。为了完整性，本发明的任何‘破坏性’切割位点可以单独用作本发明多肽的‘活化’位点。
因此，根据该实施方案，本发明提供了可在位点外(off-site)位置被可控制地失活和/或破坏的多肽。
在优选实施方案中，所述破坏性切割位点被第二蛋白酶(即，破坏性蛋白酶)识别并切割，所述第二蛋白酶选自循环蛋白酶(例如，胞外蛋白酶，例如血清蛋白酶或凝血级联的蛋白酶)、组织相关蛋白酶(例如，基质金属蛋白酶(MMP)，例如肌肉的MMP)和细胞内蛋白酶(优选靶细胞不存在的蛋白酶)。
因此，在使用中，如果本发明多肽分散远离其预期靶细胞和/或被非靶细胞摄取，则所述多肽将通过破坏性切割位点的切割(通过第二蛋白酶)而被失活。
在一个实施方案中，所述破坏性切割位点被位点外细胞类型中存在的第二蛋白酶识别并切割。在该实施方案中，位点外细胞和靶细胞优选为不同的细胞类型。可选地(或附加地)，破坏性切割位点被位点外位置(例如靶细胞的远端)存在的第二蛋白酶识别并切割。因此，当破坏性切割在细胞外发生时，靶细胞和位点外细胞可以是相同或不同的细胞类型。就这一点而言，靶细胞和位点外细胞可以各自具有与本发明相同多肽结合的受体。
本发明破坏性切割位点在所述多肽处于位点外位置中或位点外位置处时提供所述多肽的失活/破坏。就这方面而言，在破坏性切割位点处的切割使多肽效价最小化(当与缺少相同的破坏性切割位点或具有相同的破坏性位点但是为未切割形式的相同多肽相比较)。作为实例，减小的效价包括：降低的结合(与哺乳动物细胞受体)和/或减少的易位(向胞质溶胶方向跨哺乳动物细胞的内体膜)和/或减少的SNARE蛋白切割。
当选择本发明上下文中的破坏性切割位点时，优选地，所述破坏性切割位点不是可以单独用于作为其生产过程的一部分的本发明多肽的翻译后修饰的任何蛋白酶的底物。就这方面而言，本发明非细胞毒性蛋白酶通常采用蛋白酶活化事件(通过单独的‘活化’蛋白酶切割位点，其在结构上不同于本发明的破坏性切割位点)。活化切割位点的目的是切割非细胞毒性蛋白酶与本发明多肽的易位组分或结合组分之间的肽键，从而提供其中所述两个组分通过二硫键连接在一起的‘活化’双链多肽。
因此，为了帮助确保本发明多肽的破坏性切割位点不负面影响‘活化’切割位点和随后的二硫键形成，前者优选被引入本发明多肽中距离‘活化’切割位点至少20、至少30、至少40、至少50和更优选至少60、至少70、至少80个(连续的)氨基酸残基的位置。
破坏性切割位点和活化切割位点相对于多肽的天然组分而言优选是外源的(即，改造/人工的)。换言之，所述切割位点优选不是多肽相应天然组分所固有的。作为实例，基于BoNT/A L-链或H-链(分别地)的蛋白酶或易位组分可以根据本发明被改造而包括切割位点。但是，所述切割位点不会存在于相应的BoNT天然L-链或H-链。类似地，当多肽的靶向部分组分被改造为包括蛋白酶切割位点时，所述切割位点不会存在于相应靶向部分的相应天然序列中。
在本发明的优选实施方案中，破坏性切割位点和‘活化’切割位点不被同一蛋白酶切割。在一个实施方案中，两个切割位点彼此不同，因为各自识别序列内的耐受氨基酸的至少一个、更优选至少两个、特别优选至少三个和最优选至少四个是不同的。
作为实例，在梭菌L-链和HN组分之间含有Xa因子‘活化’位点的多肽嵌合体的情况下，优选在非Xa因子位点的位点采用破坏性切割位点，其被插入L-链和/或HN和/或TM组分中的其他地方。这种情况下，多肽可以被修饰以在L-链和HN组分之间容纳可选的‘活化’位点(例如，肠激酶切割位点)，这种情况下，单独的Xa因子切割位点可以作为破坏性切割位点在其他地方被并入所述多肽。可选地，L-链和HN组分之间存在的Xa因子‘活化’位点可以被保留，并且诸如凝血酶切割位点的可选切割位点作为破坏性切割位点被并入。
当在本发明任何组分的一级序列中鉴定用于加入切割位点的适合位点时，优选选择与将要插入的建议切割位点密切匹配的一级序列。通过这样做，最小的结构变化被引入多肽。作为实例，切割位点通常包括至少3个连续的氨基酸残基。因此，在优选的实施方案中，选择已经具有(在正确的位置)为引入新切割位点所需要的氨基酸残基的至少一个、优选至少两个的切割位点。作为实例，在一个实施方案中，胱天蛋白酶3切割位点(DMQD)可以被引入。就这方面而言，优选的插入位置被鉴定，其已经包括选自例如Dxxx、xMxx、xxQx、xxxD、DMxx、DxQx、DxxD、xMQx、xMxD、xxQD、DMQx、xMQD、DxQD和DMxD的一级序列。
类似地，优选将切割位点引入表面暴露的区域。在表面暴露区域内，存在的环区域是优选的。
在本发明优选实施方案中，破坏性切割位点被引入在下述位置的一个或多个，其基于BoNT/A的一级氨基酸序列。虽然插入位置是参考BoNT/A被鉴定的(为了方便)，但是可选蛋白酶结构域和/或易位结构域的一级氨基酸序列可以容易地与所述BoNT/A位置对齐。
对于蛋白酶组分，优选下述位置的一个或多个：27-31、56-63、73-75、78-81、99-105、120-124、137-144、161-165、169-173、187-194、202-214、237-241、243-250、300-304、323-335、375-382、391-400和413-423。以上编号优选始于本发明蛋白酶组分的N-末端。
在优选实施方案中，破坏性切割位点位于距离蛋白酶组分N-末端大于8个氨基酸残基、优选大于10个氨基酸残基、更优选大于25个氨基酸残基、特别优选大于50个氨基酸残基的位置。类似地，在优选实施方案中，破坏性切割位点位于距离蛋白酶组分C-末端大于20个氨基酸残基、优选大于30个氨基酸残基、更优选大于40个氨基酸残基、特别优选大于50个氨基酸残基的位置。
对于易位组分，优选下述位置的一个或多个：474-479、483-495、507-543、557-567、576-580、618-631、643-650、669-677、751-767、823-834、845-859。上述编号优选明确本发明易位结构域组分的N-末端449起始位置和易位结构域组分C-末端871终止位置。
在优选实施方案中，破坏性切割位点位于从易位组分N-末端大于10个氨基酸残基、优选大于25个氨基酸残基、更优选大于40个氨基酸残基、特别优选大于50个氨基酸残基的位置。类似地，在优选实施方案中，破坏性切割位点位于从易位组分C-末端大于10个氨基酸残基、优选大于25个氨基酸残基、更优选大于40个氨基酸残基、特别优选大于50个氨基酸残基的位置。
在优选实施方案中，破坏性切割位点位于从TM组分N-末端大于10个氨基酸残基、优选大于25个氨基酸残基、更优选大于40个氨基酸残基、特别优选大于50个氨基酸残基的位置。类似地，在优选实施方案中，破坏性切割位点位于从TM组分C-末端大于10个氨基酸残基、优选大于25个氨基酸残基、更优选大于40个氨基酸残基、特别优选大于50个氨基酸残基的位置。
本发明多肽可以包括一个或多个(例如两个、三个、四个、五个或更多个)破坏性蛋白酶切割位点。当包括超过一个破坏性切割位点时，每个切割位点可以相同或不同。就这一点而言，超过一个破坏性切割位点的使用提供了提高的位点外失活。类似地，两个或多个不同的破坏性切割位点的使用提供了额外的设计灵活性。
破坏性切割位点可以被加入下述多肽组分的任何一个中：非细胞毒性蛋白酶组分；易位组分；靶向部分；或间隔肽(如果存在)。就这一点而言，破坏性切割位点被选择以确保对多肽效价的不利影响最小(例如，通过对靶向/结合区和/或易位结构域、和/或对非细胞毒性蛋白酶结构域的影响最小)，同时确保多肽远离其靶位点/靶细胞时不稳定。
优选的破坏性切割位点(加上相应的第二蛋白酶)列于下表中。所列切割位点纯粹是示例说明性的并且不是要限制本发明。
基质金属蛋白酶(MMP)是本发明上下文中一组优选的破坏性蛋白酶。在该组中，ADAM17(EC 3.4.24.86，还称为TACE)是优选的，并且切割多种膜锚定的细胞表面蛋白以“除掉”细胞外结构域。其他优选的MMP包括蛇毒蛋白酶、serralysin和虾红素。
另一组优选的破坏性蛋白酶是哺乳动物血液蛋白酶，例如凝血酶、凝血因子VIIa、凝血因子IXa、凝血因子Xa、凝血因子XIa、凝血因子XIIa、激肽释放酶、蛋白C和MBP-相关的丝氨酸蛋白酶。
在本发明的一个实施方案中，所述破坏性切割位点包括具有至少3或4个、优选5或6个、更优选6或7个和特别优选至少8个连续氨基酸残基的识别序列。就这一点而言，识别序列越长(就连续氨基酸残基而言)，破坏性位点发生经由非预期第二蛋白酶的非特异性切割的可能性越小。
优选地，本发明的破坏性切割位点被引入蛋白酶组分和/或靶向部分和/或易位组分和/或间隔肽。这四种组分中，蛋白酶组分是优选的。因此，多肽可通过直接破坏非细胞毒性蛋白酶和/或结合和/或易位组分而被快速失活。
多肽递送
在使用中，本发明采用药物组合物，包含多肽与至少一种选自以下的组分：药学可接受的载体、赋形剂、佐剂、推进剂和/或盐。
本发明多肽可以被配制用于口服、胃肠外、连续输注、吸入或局部应用。适合注射的组合物可以是溶液、悬液或乳液、或者干燥粉末的形式，所述干燥粉末在使用前溶解或悬浮于适合媒介物中。
局部递送方式可以包括气溶胶或其他喷雾剂(例如喷雾器)。就这方面而言，多肽的气溶胶制剂能够递送至肺和/或其他鼻和/或支气管或气道通道。
优选的施用途径选自：合成(例如iv)、腹腔镜和/或局部注射(经蝶骨直接注射入垂体)。
在注射制剂情况下，任选包括药学活性物质以帮助多肽保留或减少多肽从施用部位的去除。此类药学活性物质的一个实例是血管收缩剂，例如肾上腺素。此类制剂具有增加多肽施用后驻留时间并因此增加和/或增强其效应的优点。
本发明多肽施用的剂量范围是产生希望的治疗效应的那些。应该理解，所需剂量范围取决于多肽或组合物的准确性质、施用途径、制剂性质、患者年龄、患者病症的性质、程度或严重度、禁忌症(如果有)和主治医生的判断。这些剂量水平的变化可以利用标准经验优化惯例来调整。
适合的日剂量(每kg患者体重)在0.0001-1mg/kg、优选0.0001-0.5mg/kg、更优选0.002-0.5mg/kg和特别优选0.004-0.5mg/kg的范围内。单位剂量可以从小于1毫克至30mg变化，但是通常在每剂0.01至1mg的范围内，其可以每日一次施用或优选以更低频率施用，例如每周一次或每月六次。
特别优选的给药方案是基于2.5ng多肽作为1X剂。就这方面而言，优选的剂量范围1X-100X(即2.5-250ng)。
流体剂型通常使用多肽和无热原无菌媒介物来制备。根据使用的媒介物和浓度，多肽可以溶解或悬浮于媒介物。在制备溶液时，多肽可以溶解于媒介物，如果必要，可以通过添加氯化钠而使溶液成为等渗的并且在填入适合无菌管或安瓿并密封之前使用无菌技术通过无菌滤器过滤而使溶液无菌。可选地，如果溶液稳定性足够，在其密封容器中的溶液可以通过高压灭菌来灭菌。有利地，诸如缓冲剂、溶解剂、稳定剂、防腐剂或杀菌剂、悬浮剂或乳化剂和或局部麻醉剂的添加剂可以被溶解于媒介物中。
在使用前溶解或悬浮于适合媒介物中的干燥粉末可以通过在无菌区使用无菌技术将预灭菌的成分填入无菌容器来制备。可选地，所述成分可以在无菌区使用无菌技术溶入适合容器。然后将产物冷冻干燥并无菌密封容器。
适合肌肉内、皮下或皮内注射的胃肠外悬液以基本上相同的方式制备，除了无菌组分悬浮于无菌媒介物而不是被溶解，并且灭菌不能通过过滤来实现。组分可以无菌状态被分离，或者可选地其可以在分离后被灭菌，例如通过γ辐照。
有利地，悬浮剂例如聚乙烯比咯烷酮被加入组合物以促进组分的均一分布。
定义部分
靶向部分(TM)指在功能上与结合位点相互作用而导致本发明多肽与靶细胞(通常是哺乳动物细胞，特别是人细胞)表面之间物理缔合的任何化学结构。术语TM包括能够与靶细胞上的结合位点结合的任何分子(即，天然存在的分子，或其化学/物理修饰的变体)，所述结合位点能够内化(例如内体形成)–还称为受体介导的胞吞。TM可以具有内体膜易位功能，在这种情况下，单独TM和易位结构域组分不需要存在于本发明物质中。在前述说明书中，已经描述了具体的TM。对所述TM的提及仅是示例性的，并且本发明包括其所有变体和衍生物，其对生长激素释放细胞上的结合位点具有结合(即，靶向)能力，其中所述结合位点能够内化。
本发明TM结合(优选特异性结合)关注的靶细胞。术语“特异性结合”优选指给定TM以106M-1或更大例如107M-1或更大、108M-1或更大、109M-1或更大的结合亲和力(Ka)结合靶细胞。
本说明书中对TM的提及包括其片段和变体，其保留结合关注的靶细胞的能力。作为实例，变体可以与参考TM具有至少80％、优选至少90％、更优选至少95％和最优选至少97或至少99％的氨基酸序列同源性。因此，变体可以包括氨基酸的一种或多种类似物(例如非天然氨基酸)或取代的键合。而且，作为实例，当与TM相关使用时，术语片段指具有参考TM的至少10个、优选至少20个、更优选至少30个和最优选至少40个氨基酸残基的肽。术语片段还涉及上述变体。因此，作为实例，本发明片段可以包括具有至少10、20、30或40个氨基酸的肽序列，其中所述肽序列与参考肽的相应肽序列(连续)氨基酸具有至少80％序列同源性。
作为实例，ErbB肽TM可以被修饰以产生具有改变的性质(例如增加的稳定性)的突变蛋白ErbB配体。作为实例，ErbB TM突变蛋白包括具有氨基酸修饰的ErbB肽，所述氨基酸修饰例如在位置46或47处的缬氨酸(EGFVal46或47)，其赋予细胞蛋白酶稳定性。ErbB TM还可以具有氨基酸缺失或额外的氨基酸插入。这包括但不限于：具有两个C-末端氨基酸缺失和位置51的中性氨基酸取代的EGF(特别是EGF51Gln51；参见US20020098178A1)，和具有氨基酸缺失的EGF(例如rEGF2-48；rEGF3-48和rEGF4-48)。ErbB TM的片段可以包括TGFα的片段，其含有预测的β-转角区(例如，序列Ac-C-H-S-G-Y-V-G-A-R-C-O-OMe的肽)，EGF的片段，例如[Ala20]EGF(14-31)，和肽YHWYGYTPQNVI或GE11。所有上述专利说明书在此通过引用并入。
作为进一步实例，促生长素抑制素(SST)和皮质抑素(CST)具有高结构同源性，并结合所有已知的SST受体。全长SST具有氨基酸序列：
MLSCRLQCALAALSIVLALGCVTGAPSDPRLRQFLQKSLAAAAGKQELAKYFLAELLSEPNQTENDALEPEDLSQAAEQDEMRLELQRSANSNPAMAPRERKAGCKNFFWKTFTSC
全长CST具有氨基酸序列：
MYRHKNSWRLGLKYPPSSKEETQVPKTLISGLPGRKSSSRVGEKLQSAHKMPLSPGLLLLLLSGATATAALPLEGGPTGRDSEHMQEAAGIRKSSLLTFLAWWFEWTSQASAGPLIGEEAREVARRQEGAPPQQSARRDRMPCRNFFWKTFSSCK
对这些TM的提及包括其下述片段(和相应变体)：
NFFWKTF；
(R或K)NFFWKTF；
C(R或K)NFFWKTF；
(P或G)C(R或K)NFFWKTF；
NFFWKTF(S或T)；
NFFWKTF(S或T)S；
NFFWKTF(S或T)SC；
(R或K)NFFWKTF(S或T)；
(R或K)NFFWKTF(S或T)S；
(R或K)NFFWKTF(S或T)SC；
C(R或K)NFFWKTF(S或T)；
C(R或K)NFFWKTF(S或T)S；
C(R或K)NFFWKTF(S或T)SC；
(P或G)C(R或K)NFFWKTF(S或T)；
(P或G)C(R或K)NFFWKTF(S或T)S；或
(P或G)C(R或K)NFFWKTF(S或T)C.
就上述序列而言，当给出(P或G)二选一时，P在CST TM情况下是优选的，而G在SSTTM情况下是优选的。当给出(R或K)二选一时，R在CST TM情况下是优选的，而K在SST TM情况下是优选的。当给出(S或T)二选一时，S在CST TM情况下是优选的，而T在SST TM情况下是优选的。
优选的片段包括至少7或至少10个氨基酸残基，优选至少14或至少17个氨基酸残基，并且更优选至少28或29个氨基酸残基。作为实例，优选的序列包括：
SANSNPAMAPRERKAGCKNFFWKTFTSC(SST-28)；
AGCKNFFWKTFTSC(SST-14)；
QEGAPPQQSARRDRMPCRNFFWKTFSSCK(CST-29)；
QERPPLQQPPHRDKKPCKNFFWKTFSSCK(CST-29)；
QERPPPQQPPHLDKKPCKNFFWKTFSSCK(CST-29)
DRMPCRNFFWKTFSSCK(CST-17)；
PCRNFFWKTFSSCK(CST-14)；和
PCKNFFWKTFSSCK(CST-14)
TM可以包括较长的氨基酸序列，例如至少30或35个氨基酸残基，或至少40或45个氨基酸残基，只要TM能够结合正常的GH-分泌细胞、优选结合正常GH-分泌细胞上的SST或CST受体。就这方面而言，TM优选是全长SST或CST的片段，但是包括至少核心序列“NFFWKTF”或上述一级氨基酸序列之一。
作为进一步实例，本发明的GHRH肽包括：
常规证实TM结合选定的靶细胞。例如，可以采用简单的放射性位移实验，其中生长激素分泌细胞的代表性组织或细胞在过量未标记TM存在下被暴露于标记的(例如氚化的)TM。在这样的实验中，非特异性和特异性结合的相对比例可以被测定，从而允许证实TM结合靶细胞。任选地，所述测定可以包括一种或多种结合拮抗剂，并且所述测定还可包括观察TM结合的丧失。该类型实验的实例可以见于Hulme,E.C.(1990),receptor-binding studies,a brief outline(受体结合研究概要),第303-311页,于Receptor biochemistry,APractical Approach(受体生物化学实践方法),编辑E.C.Hulme,Oxford UniversityPress。
在本发明上下文中，对肽TM的提及(例如GHRH肽或瘦蛋白肽)包括其肽类似物，只要所述类似物结合与相应‘参考‘TM相同的受体。所述类似物可以包括如下合成残基：
β-Nal＝β-萘丙氨酸
β-Pal＝β-吡啶丙氨酸
hArg(Bu)＝N-胍基-(丁基)-高精氨酸
hArg(Et)2＝N,N'-胍基-(二甲基)-高精氨酸
hArg(CH2CF3)2＝N,N-胍基-二-(2,2,2,-三氟乙基)-高精氨酸
hArgg(CH2,己基)＝N,N-胍基-(甲基，己基)-高精氨酸
Lys(Me)＝Ne-甲基赖氨酸
Lys(iPr)＝Ne-异丙基赖氨酸
AmPhe＝氨基甲基苯丙氨酸
AChxAla＝氨基环己基丙氨酸
Abu＝α-氨基丁酸
Tpo＝4-硫代脯氨酸
MeLeu＝N-甲基亮氨酸
Orn＝鸟氨酸
Nle＝正亮氨酸
Nva＝正缬氨酸
Trp(Br)＝5-溴-色氨酸
Trp(F)＝5-氟-色氨酸
Trp(N02)＝5-硝基-色氨酸
Gaba＝γ-氨基丁酸
Bmp＝J-巯丙酰基
Ac＝乙酰基
Pen＝青霉胺
作为实例，上述肽类似物方面参考具体肽TM被更详细描述，所述肽例如SST肽、GHRH肽、铃蟾肽、生长素释放肽和尿紧张素肽，但是本发明所有TM适用相同原理。
可用于实施本发明的促生长素抑制素类似物包括但不限于在此通过引用并入的下述出版物中描述的那些：Van Binst,G.等.Peptide Research 5:8(1992)；Horvath,A.等Abstract,“Conformations of somatostatin Analogs Having Antitumor Activity(具有抗肿瘤活性的促生长素抑制素类似物的构象)”,第22届欧洲肽专题报告,1992年9月13-19日,Interlaken,Switzerland；US5,506,339；EP0363589；US4,904,642；US4,871,717；US4,725,577；US4,684,620；US4,650,787:US4,585,755；US4,725,577；US4,522,813；US4,389,179；US4,360,516；US4,328,214；US4,316,890；US4,310,518；US4,291,022；US4,238,481；US4,235,886；US4,211,693；US4,190,648；US4,148,612；US4,133,782；US5,506,339:US4,261,885；US4,282,143；US4,190,575；US5,552,520；EP0389180；EP0505680；US4,603,120；EP0030920；US4,853,371；WO90/12811；WO97/01579；WO91/18016；WO98/08529和WO98/08528；WO/0075186和WO00/06185；WO99/56769；和FR2,522,855。这些出版物的每一个通过引用整体并入。
用于合成类似物的方法被良好记载，如例如上述引用专利所描述的。例如，H-D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2的合成可以通过按照EP0395417A1的实施例1所述方案来实现。类似地，合成具有取代的N-末端的类似物可以例如通过按照WO88/02756、EP0329295和US5,240,561中所述方案来实现。
线性SST类似物的使用也包括在本发明范围内，例如H-D-Phe-p-氯-Phe-Tyr-D-Trp-Lys-Thr-Phe-Thr-NH2；H-D-Phe-p-NO2-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr-NH2；H-D-*Nal-p-氯-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr-NH2；H-D-Phe-Phe-Phe-D-Trp-Lys-Thr-Phe-Thr-NH2；H-D-Phe-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr-NH2；H-D-Phe-p-氯-Phe-Tyr-D-Trp-Lys-Val-Phe-Thr-NH2；和H-D-Phe-Ala-Tyr-D-Trp-Lys-Val-Ala-D-β-Nal-NH2。
一个或多个化学部分，例如糖衍生物、单或多羟基(C2-12)烷基、单或多羟基(C2-12)酰基或哌嗪衍生物可以连接至SST类似物，例如连接至N-末端氨基酸-参见WO88/02756、EP0329295、和US5,240,561。
GHRH肽类似物追溯到二十世纪九十年代，并且包括‘标准拮抗剂’[Ac-Tyr1、D-Arg2jhGH-RH(1-29)Nha。美国专利4,659,893公开了在GH-RH(1-29)序列的位置2含有确定的N,N'-二烷基-ω-胍基α-氨基酰基残基的GH-RH拮抗类似物。其他实例提供于WO91/16923、US 5,550.212、US5,942,489、US6,057,422、US5,942,489、US6,057,422、WO96/032126、WO96/022782、WO98/016707、WO94/011397、WO94/011396，其每一个在此通过引用并入。
适用于本发明的铃蟾肽类似物的实例包括包含以下的TM：D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2(代号为BIM-26218)、D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2(代号为BIM-26187)；D-Cpa-Gln-Trp-Ala-Val-Gly-His-Leu-[CH2NH]-Phe-NH2(代号为BIM-26159)和D-Phe-Gln-Trp-Ala-Val-Gly-His-Leu-[CH2NH]-Cpa-NH2；(代号为BIM-26189)；D-Phe-Gln-Trp-Ala-Val-N-甲基-D-Ala-His-Leu-甲基酯、和D-F9-Phe-Gln-Trp-Ala-Val-D-Ala-His-Leu-甲基酯。
铃蟾肽类似物包括衍生自下述的肽：天然存在的结构相关的肽，即，铃蟾肽、神经调节肽B、神经调节肽C、雨滨蛙肽和GRP。这些天然存在的TM肽的相关氨基酸序列列于以下：
铃蟾肽(后10个aa):Gly-Asn-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2
神经调节肽B:Gly-Asn-Leu-Trp-Ala-Thr-Gly-His-Phe-Met-NH2
神经调节肽C:Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2
雨滨蛙肽:pGlu-Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH2
人GRP(后10个aa):Gly-Asn-His-Trp-Ala-Val-Gly-His-Leu-Met-NH2
适用于本发明的类似物描述于1990年3月30日提交的美国序号502,438，1989年8月21日提交的美国序号397,169，1989年7月7日提交的美国序号376,555，1989年8月16日提交的美国序号394,727，1988年3月2日提交的美国序号317,941，1988年12月9日提交的美国序号282,328，1988年10月14日提交的美国序号257,998，1988年9月23日提交的美国序号248,771，1988年6月16日提交的美国序号207,759，1988年6月8日提交的美国序号204,171，1988年3月25日提交的美国序号173,311，1987年9月24日提交的美国序号100,571，和1990年5月9日提交的美国序号520,225，1989年11月21日提交的美国序号440,039。所有这些申请在此通过引用并入。铃蟾肽类似物还描述于Zachary等,Proc.Nat.Aca.Sci.82:7616(1985)；Heimbrook等,"Synthetic Peptide:Approaches to Biological Problems(合成肽：生物问题的解决方法",UCLA专题报告，Mol.and Cell.Biol.New Series,88卷,编辑Tarn和Kaiser；Heinz-Erian等,Am.J.Physiol.G439(1986)；Martinez等,J.Med.Chem.28:1874(1985)；Gargosky等,Biochern.J.247:427(1987)；Dubreuil等,Drug Design andDelivery,卷2:49,Harwood Academic Publishers,GB(1987)；Heikkila等J.Biol.Chem.262:16456(1987)；Caranikas等,J.Med.Chem.25:1313(1982)；Saeed等,Peptide 10:597(1989)；Rosell等,Trends in Pharmacological Sciences 3:211(1982)；Lundberg等Proc.Nat.Aca.Sci.80:1120,(1983)；Engberg等,Nature 293:222(1984)；Mizrahi等,Euro.J.Pharma.82:101(1982)；Leander等,Nature 294:467(1981)；Woli等,Biochem.Biophys.Res.Comm.155:359(1988)；Rivier等,Biochem.17:1766(1978)；Cuttitta等,Cancer Surveys 4:707(1985)；Aumelas等,Int.J.Peptide Res.30:596(1987)；全部也在此通过引用并入。
类似物可通过常规技术制备，例如WO92/20363和EP0737691中描述的那些。其他铃蟾肽类似物描述于例如WO89/02897、WO91/17181、WO90/03980和WO91/02746，全部在此通过引用并入。
适合用作本发明TM的生长素释放肽类似物的实例包括：Tyr-DTrp-DLys-Trp-DPhe-NH2、Tyr-DTrp-Lys-Trp-DPhe-NH2、His-DTrp-DLys-Trp-DPhe-NH2、His-DTrp-DLys-Phe-DTrp-NH2、His-DTrp-DArg-Trp-DPhe-NH2、His-DTrp-DLys-Trp-DPhe-Lys-NH2、去氨基Tyr-DTrp-Ala-Trp-DPhe-NH2、去氨基Tyr-DTrp-DLys-Trp-DPhe-NH2、去氨基Tyr-DTrp-Ser-Trp-DPhe-Lys-NH2、去氨基Tyr-DTrp-Ser-Trp-DPhe-NH2、His-DTrp-DTrp-Phe-Met-NH2、Tyr-DTrp-DTrp-Phe-Phe-NH2、Glyψ[CH2NH]-DβNal-Ala-Trp-DPhe-Lys-NH2、Glyψ[CH2NH]-DβNal-DLyS-TrP-DPhe-Lys-NH2、DAla-DβNal-DLys-DTrp-Phe-Lys-NH2、His-DβNal-DLys-Trp-DPhe-Lys-NH2、Ala-His-DTrp-DLys-Trp-DPhe-Lys-NH2、[CH2NH]-DβNal-Ala-Trp-DPhe-Lys-NH2、DβNal-Ala-Trp-DPhe-Ala-NH2、DAla-D环己基Ala-Ala-Phe-DPhe-Nle-NH2、D环己基Ala-Ala-Phe-DTrp-Lys-NH2、DAla-DβAla-Thr-DThr-Lys-NH2、D环己基Ala-Ala-Trp-DPhe-NH2、DAla-DβNal-Ala-Ala-DAla-Lys-NH2、DβNal-Ala-Trp-DPhe-Leu-NH2、His-DTrp-Phe-Trp-DPhe-Lys-NH2、DAla-DβNal-DAla-DTrp-Phe-Lys-NH2、pAla-Trp-DAla-DTrp-Phe-NH2、His-Trp-DAla-DTrp-Phe-Lys-NH2、DLys-DβNal-Ala-Trp-DPhe-Lys-NH2、DAla-DβNal-DLys-DTrp-Phe-Lys-NH2、Tyr-DAla-Phe-Aib-NH2、Tyr-DAla-Sar-NMePhe-NH2、αγAbu-DTrp-DTrp-Ser-NH2、αγAbu-DTrp-DTrp-Lys-NH2、αγAbu-DTrp-DTrp-Orn-NH2、αAbu-DTrp-DTrp-Orn-NH2、DThr-DαNal-DTrp-DPro-Arg-NH2、DAla-Ala-DAla-DTrp-Phe-Lys-NH2、Alaψ[CH2NH]His-DTrp-Ala-Trp-DPhe-Lys-NH2、Lys-DHis-DTrp-Phe-NH2、γAbu-DTrp-DTrp-Orn-NH2、inip-Trp-Trp-Phe-NH2、Ac-DTrp-Phe-DTrp-Leu-NH2、Ac-DTrp-Phe-DTrp-Lys-NH2、Ac-DTrp-DTrp-Lys-NH2、DLys-Tyr-DTrp-DTrp-Phe-Lys-NH2、Ac-DβNal-Leu-Pro-NH2、pAla-Trp-DTrp-DTrp-Orn-NH2、DVal-DαNal-DTrp-Phe-Arg-NH2、DLeu-DαNal-DTrp-Phe-Arg-NH2、环己基Ala-DαNal-DTrp-Phe-Arg-NH2、DTp-DαNal-DTrp-Phe-Arg-NH2、DAla-DβNal-DPro-Phe-Arg-NH2、Ac-DαNal-DTrp-Phe-Arg-NH2、DαNal-DTrp-Phe-Arg-NH2、His-DTrp-DTrp-Lys-NH2、Ac-DpNal-DTrp-NH2、αAib-DTrp-D环己基Ala-NH2、αAib-DTrp-DAla-环己基Ala-NH2、DAla-D环己基Ala-Ala-Ala-Phe-DPhe-Nle-NH2、DPhe-Ala-Phe-DPal-NH2、DPhe-Ala-Phe-DPhe-Lys-NH2、DLys-Tyr-DTrp-DTrp-Phe-NH2、Ac-DLys-Tyr-DTrp-DTrp-Phe-NH2、Arg-DTrp-Leu-Tyr-Trp-Pro(环Arg-Pro)、Ac-DβNal-PicLys-ILys-DPhe-NH2、DPal-Phe-DTrp-Phe-Met-NH2、DPhe-Trp-DPhe-Phe-Met-NH2、DPal-Trp-DPhe-Phe-Met-NH2、pAla-Pal-DTrp-DTrp-Orn-NH2、αγAbu-Trp-DTrp-DTrp-Orn-NH2、βAla-Trp-DTrp-DTrp-Lys-NNH2、γAbu-Trp-DTrp-DTrp-Orn-NH2、Ava-Trp-DTrp-DTrp-Orn-NH2、DLys-Tyr-DTrp-Ala-Trp-DPhe-NH2、His-DTrp-DArg-Trp-DPhe-NH2、<Glu-His-Trp-DSer-DArg-NH2、DPhe-DPhe-DTrp-Met-DLys-NH2、0-(2-甲基烯丙基)二苯甲酮肟、(R)-2-氨基-3-(1H-吲哚-3-基)-l-(4-苯基哌啶-1-基)丙-1-酮、N-((R)-1-((R)-1-((S)-3-(1H-吲哚-3-基)-1-氧-1-(4-苯基哌啶-1-基)丙-2-基氨基)-6-氨基-1–氧己-2-基氨基)-3-羟基-1–氧丙-2-基)苯酰胺、(S)-N-((S)-3-(1H-吲哚-3-基)-1–氧-1-(4-苯基哌啶-1基)丙-2-基)-6-乙酰胺-2-((S)-2-氨基-3-(苄氧基)丙酰胺)己酰胺、(S)-N-((R)-3-(1H-吲哚-3-基)-1-氧-1-(4-苯基哌啶-1–基)丙-2-基)-2-((S)-2-乙酰胺-3-(苄氧基)丙酰胺)-6-氨基己酰胺、(R)-N-(3-(1H-吲哚-3-基}-1-(4-(2-甲氧基苯基)哌啶-1–基)-1–氧丙-2-基)-4-氨基丁酰胺、(R)-N-(3-(1H-吲哚-3-基)-1-(4-(2-甲氧基苯基)哌啶-1–基)-1–氧丙-2-基)-2-氨基-2-甲基丙酰胺、3(p-甲苯基氨基甲酰基)-2-萘甲酸甲酯、3-(4-(2-甲氧基苯基)哌啶-1–羰基)-2-萘甲酸乙酯、3-(2-甲氧基苯基氨基甲酰基)-2-萘酸酯、(S)-2,4-二氨基-N-((R)-3-(萘-2-基甲氧基)-1-氧-1-(4-苯基哌啶-1–基)丙-2-基)丁酰胺、萘-2,3-二基双((4-(2-甲氧基苯基)哌嗪-1-基)甲酮)、(R)-2-氨基-N-(3-(苄氧基)-1–氧-1-(4-苯基哌嗪-1–基)丙-2-基)-2-甲基丙酰胺、或(R)-2-氨基-3-(苄氧基)-1-(4-苯基哌嗪-1–基)丙-1–酮。
适用于本发明TM的硬骨鱼紧张肽的实例包括：Cpa-c[D-Cys-Phe-Trp-Lys-Thr-Cys]-Val-NH2；和Asp-c[Cys-Phe-Trp-Lys-Tyr-Cys]-Val-OH。
本发明多肽缺乏梭菌神经毒素的功能性HC结构域。因此，所述多肽在Shone等(1985)Eur.J.Biochem.151,75-82所述结合分析中不能结合大鼠突触膜(经由梭菌HC组分)。在优选实施方案中，所述多肽优选缺乏梭菌神经毒素全毒素的后50个C-末端氨基酸。在另一个实施方案中，所述多肽优选缺乏梭菌神经毒素全毒素的后100个、优选后150个、更优选后200个、特别优选后250个和最优选后300个C-末端氨基酸残基。可选地，Hc结合活性可以通过诱变被无效/降低–作为实例，为方便参考BoNT/A，神经节苷脂结合口袋中一个或两个氨基酸残基突变(W1266至L和Y1267至F)的修饰导致HC区失去其受体结合功能。可以对非血清型A梭菌肽组分进行类似突变，所述组分例如基于肉毒杆菌B而具有突变(W1262至L和Y1263至F)或肉毒杆菌E(W1224至L和Y1225至F)的构建体。活性位点的其他突变同样实现了HC受体结合活性的消除，例如在肉毒杆菌A型毒素中的Y1267S和其他梭菌神经毒素中相应高度保守的残基。该突变和其他突变的细节描述于Rummel等(2004)(MolecularMicrobiol.51:631-634)，其在此通过引用并入。
在另一个实施方案中，本发明多肽缺乏梭菌神经毒素的功能性HC结构域，并且还缺乏任何功能上等效的TM。因此，所述多肽缺乏梭菌神经毒素的天然结合功能，并且在Shone等(1985)Eur.J.Biochem.151,75-82所述结合分析中不能结合大鼠突触膜(经由梭菌HC组分，或经由任何功能上等效的TM)。
在一个实施方案中，TM优选不是小麦胚凝集素(WGA)肽。
天然梭菌神经毒素的Hc肽包括大约400-440个氨基酸残基，并且由各自大约25kDa的两个功能上不同的结构域，即N-末端区(常称为HCN肽或结构域)和C-末端区(常称为HCC肽或结构域)组成。该事实通过每一个在此通过引用整体并入的下述出版物证实：Umland TC(1997)Nat.Struct.Biol.4:788-792；Herreros J(2000)Biochem.J.347:199-204；HalpernJ(1993)J.Biol.Chem.268:15,第11188-11192页；Rummel A(2007)PNAS 104:359-364；Lacey DB(1998)Nat.Struct.Biol.5:898-902；Knapp(1998)Am.Cryst.Assoc.AbstractPapers 25:90；Swaminathan和Eswaramoorthy(2000)Nat.Struct.Biol.7:1751-1759；和Rummel A(2004)Mol.Microbiol.51(3),631-643。然而，已经良好记录了构成C-末端160-200氨基酸残基的C-末端区(HCC)负责梭菌神经毒素与其天然细胞受体结合，即与神经肌肉接合处的神经末梢结合–该事实也被上述出版物证实。因此，本说明书通篇对缺乏功能性重链HC肽(或结构域)以使重链不能结合与天然梭菌神经毒素结合的细胞表面受体的梭菌重链的提及，意味着所述梭菌重链仅缺乏功能性HCC肽。换言之，HCC肽区是部分或完全缺失，或者以其他方式被修饰(例如，通过常规的化学或蛋白水解处理)以失活其对神经肌肉接合处的神经末梢的天然结合能力。
因此，在一个实施方案中，本发明的梭菌HN肽缺乏梭菌神经毒素的C-末端肽部分(HCC)的部分，并因此缺乏天然梭菌神经毒素的HC结合功能。作为实例，在一个实施方案中，C-末端延伸的梭菌HN肽缺乏梭菌神经毒素重链的C-末端40个氨基酸残基、或C-末端60个氨基酸残基、或C-末端80个氨基酸残基、或C-末端100个氨基酸残基、或C-末端120个氨基酸残基、或C-末端140个氨基酸残基、或C-末端150个氨基酸残基、或C-末端160个氨基酸残基。在另一个实施方案中，本发明梭菌HN肽缺乏梭菌神经毒素的完整C-末端肽部分(HCC)，并因此缺乏天然梭菌神经毒素的HC结合功能。作为实例，在一个实施方案中，梭菌HN肽缺乏梭菌神经毒重链的C-末端165个氨基酸残基、或C-末端170个氨基酸残基、或C-末端175个氨基酸残基、或C-末端180个氨基酸残基、或C-末端185个氨基酸残基、或C-末端190个氨基酸残基、或C-末端195个氨基酸残基。作为进一步实例，本发明的梭菌HN肽缺乏选自由以下组成的组的梭菌HCC参考序列：
肉毒杆菌A型神经毒素-氨基酸残基(Y1111-L1296)
肉毒杆菌B型神经毒素-氨基酸残基(Y1098-E1291)
肉毒杆菌C型神经毒素-氨基酸残基(Y1112-E1291)
肉毒杆菌D型神经毒素-氨基酸残基(Y1099-E1276)
肉毒杆菌E型神经毒素-氨基酸残基(Y1086-K1252)
肉毒杆菌F型神经毒素-氨基酸残基(Y1106-E1274)
肉毒杆菌G型神经毒素-氨基酸残基(Y1106-E1297)
破伤风神经毒素-氨基酸残基(Y1128-D1315)。
上述参考序列应该被认为指导，因为可根据亚血清型而发生略微变化。
本发明蛋白酶包括能够切割真核细胞中细胞外融合器的一个或多个蛋白的所有非细胞毒性蛋白酶。
本发明蛋白酶优选是细菌蛋白酶(或其片段)。更优选地，细菌蛋白酶选自梭状芽孢杆菌属或奈瑟氏菌属/链球菌属(例如梭菌L-链，或奈瑟菌IgA蛋白酶，优选来自淋球菌或肺炎链球菌)。
本发明还包括变体非细胞毒性蛋白酶(即，天然存在的蛋白酶分子的变体)，只要所述变体蛋白酶依然显示必要的蛋白酶活性。作为实例，变体可以与参考蛋白酶序列具有至少70％、优选至少80％、更优选至少90％和最优选至少95或至少98％氨基酸序列同源性。因此，术语变体包括具有增强的(或降低的)内肽酶活性的非细胞毒性蛋白酶–在这里特别提及BoNT/A突变体Q161A、E54A和K165L的增加的Kcat/Km，参见Ahmed,S.A.(2008)ProteinJ.DOI 10.1007/s10930-007-9118-8,其在此通过引用并入。当与蛋白酶相关使用时，术语片段通常指具有参考蛋白酶的至少150、优选至少200、更优选至少250和最优选至少300个氨基酸残基的肽。与TM‘片段’组分(上述)一样，本发明的蛋白酶‘片段’包括基于参考序列的变体蛋白酶的片段。
本发明蛋白酶优选显示丝氨酸或金属蛋白酶活性(例如内肽酶活性)。蛋白酶优选特异性针对SNARE蛋白(例如SNAP-25、小突触泡蛋白/VAMP或突触融合蛋白)。
特别提及神经毒素的蛋白酶结构域，例如细菌神经毒素的蛋白酶结构域。因此，本发明包括天然存在的神经毒素结构域，以及以所述天然存在的神经毒素的重组制备形式的使用。
示例性的神经毒素由梭菌产生，术语梭菌神经毒素包括由破伤风梭菌(C.tetani)产生的神经毒素(TeNT)和由肉毒梭菌(C.botulinum)血清型A-G产生的神经毒素(BoNT)以及由巴氏梭菌(C.baratii)和丁酸梭菌(C.butyricum)产生的密切相关的BoNT样神经毒素。上述缩写在本说明书通篇使用。例如，术语BoNT/A指定神经毒素来源为BoNT(血清型A)。相应的术语应用于其他BoNT血清型。
BoNT是已知最有效的毒素，根据血清型，对小鼠的中值致死剂量(LD50)值范围是0.5至5ng/kg。BoNT被吸附于胃肠道，并且在进入全身循环之后，结合到胆碱能神经末梢的突触前膜，并且预防其神经递质乙酰胆碱的释放。BoNT/B、BoNT/D、BoNT/F和BoNT/G切割小突触泡蛋白/囊泡相关膜蛋白(VAMP)；BoNT/C、BoNT/A和BoNT/E切割25kDa的突触相关蛋白(SNAP-25)；并且BoNT/C切割突触融合蛋白。
BoNT共有常见的结构，是～150kDa的双链蛋白，由通过单个二硫键与～50kDa轻链(L-链)共价结合的～100kDa重链(H-链)组成。H-链由两个结构域组成，每个为～50kDa。C-末端结构域(HC)是高亲和神经结合所需的，而N-末端结构域(HN)被提出参与膜易位。L-链是负责切割底物SNARE蛋白的锌依赖性金属蛋白酶。
术语L-链片段指神经毒素L-链的组分，所述片段显示金属蛋白酶活性并且能够蛋白水解切割参与细胞胞吐的囊泡和/或质膜相关蛋白。
适合的蛋白酶(参考)序列的实例包括：
肉毒杆菌A型神经毒素 -氨基酸残基(1-448)
肉毒杆菌B型神经毒素 -氨基酸残基(1-440)
肉毒杆菌C型神经毒素 -氨基酸残基(1-441)
肉毒杆菌D型神经毒素 -氨基酸残基(1-445)
肉毒杆菌E型神经毒素 -氨基酸残基(1-422)
肉毒杆菌F型神经毒素 -氨基酸残基(1-439)
肉毒杆菌G型神经毒素 -氨基酸残基(1-441)
破伤风神经毒素 -氨基酸残基(1-457)
IgA蛋白酶 -氨基酸残基(1-959)*
*Pohlner,J.等(1987).Nature 325,第458-462页,其在此通过引用并入。
上述参考序列应该认为是指导，因为可根据亚血清型而发生略微变化。作为实例，US 2007/0166332(在此通过引用并入)引用了略微不同的梭菌序列：
肉毒杆菌A型神经毒素 -氨基酸残基(M1-K448)
肉毒杆菌B型神经毒素 -氨基酸残基(M1-K441)
肉毒杆菌C型神经毒素 -氨基酸残基(M1-K449)
肉毒杆菌D型神经毒素 -氨基酸残基(M1-R445)
肉毒杆菌E型神经毒素 -氨基酸残基(M1-R422)
肉毒杆菌F型神经毒素 -氨基酸残基(M1-K439)
肉毒杆菌G型神经毒素 -氨基酸残基(M1-K446)
破伤风神经毒素 -氨基酸残基(M1-A457)
包括轻链的多种梭菌毒素片段可用于本发明的方面，条件是这些轻链片段可以特异性靶向神经递质释放器的核心组分并因此参与执行梭菌毒素蛋白水解切割底物的总体细胞机制。梭菌毒素的轻链长度大约为420-460个氨基酸并且包括酶促结构域。研究显示梭菌毒素轻链的全长不是酶促结构域酶促活性所必需的。作为非限制性实例，BoNT/A轻链的前8个氨基酸不是酶促活性所需的。作为另一个非限制性实例，TeNT轻链的前8个氨基酸不是酶促活性所需的。同样，轻链的羧基末端不是活性所必需的。作为非限制性实例，BoNT/A轻链的后32个氨基酸(残基417-448)不是酶促活性所需的。作为另一个非限制性实例，TeNT轻链的后31个氨基酸(残基427-457)不是酶促活性所需的。因此，该实施方案的方面可以包括含有长度例如至少350个氨基酸、至少375个氨基酸、至少400个氨基酸、至少425个氨基酸和至少450个氨基酸的酶促结构域的梭菌毒素轻链。该实施方案的其他方面可以包括含有长度例如至多350个氨基酸、至多375个氨基酸、至多400个氨基酸、至多425个氨基酸和至多450个氨基酸的酶促结构域的梭菌毒素轻链。
本发明的非细胞毒性蛋白酶组分优选包括BoNT/A、BoNT/B或BoNT/D血清型L-链(或其片段或变体)。
本发明的多肽，特别是其蛋白酶组分，可以被PEG化–这可以帮助增加蛋白酶组分的稳定性，例如作用持续时间。当蛋白酶包括BoNT/A、B或C1蛋白酶时，PEG化是特别优选的。PEG化优选包括将PEG添加至蛋白酶组分的N末端。作为实例，蛋白酶的N末端可以用一个或多个可以相同或不同的氨基酸(例如半胱氨酸)残基来延伸。所述氨基酸残基的一个或多个可以具有与其连接(例如共价连接)的其自身的PEG分子。该技术的实例描述于WO2007/104567，其通过引用整体并入。
易位结构域是使蛋白酶易位至靶细胞以使蛋白酶活性在靶细胞的胞质溶胶中功能性表达的分子。任何分子(例如蛋白或肽)是否具有本发明必要的易位功能可以通过许多常规分析的任何一个来确认。
例如，Shone C.(1987)描述了采用脂质体的体外分析，所述脂质体用测试分子攻击。通过K+和/或标记的NAD从脂质体的释放确认必要易位功能的存在，所述释放可容易被监测[参见Shone C.(1987)Eur.J.Biochem；卷167(1):第175-180页]。
Blaustein R.(1987)提供了进一步的实例，描述了简单的体外分析，采用平面磷脂双层膜。所述膜用测试分子攻击并通过跨所述膜的电导增加而确认必要的易位功能[参见Blaustein(1987)FEBS Letts；第226卷,第1期:第115-120页]。
能够评估膜融合并因此鉴定适用于本发明的易位结构域的其他方法描述于Methods in Enzymology 220和221卷,Membrane Fusion Techniques(膜融合技术),部分A和B,Academic Press 1993。
本发明还包括变体易位结构域，只要变体结构域依然显示必要的易位活性。作为实例，变体可以与参考易位结构域具有至少70％、优选至少80％、更优选至少90％和最优选至少95或至少98％氨基酸序列同源性。当与易位结构域相关使用时，术语片段指具有参考易位结构域的至少20、优选至少40、更优选至少80和最优选至少100个氨基酸残基的肽。在梭菌易位结构域的情况下，片段优选具有参考易位结构域(例如HN结构域)的至少100、优选至少150、更优选至少200和最优选至少250个氨基酸残基。与TM‘片段’组分(上述)一样，本发明的易位‘片段’包括基于参考序列的变体易位结构域的片段。
易位结构域优选能够在低pH条件下在脂膜中形成离子可透性孔。优选地，已经发现仅使用能够在内体膜中形成孔的蛋白分子的那些部分。
易位结构域可以获自微生物蛋白来源，特别是获自细菌或病毒蛋白来源。因此，在一个实施方案中，易位结构域是酶的易位结构域，所述酶例如细菌毒素或病毒蛋白。
已经良好记载细菌毒素分子的某些结构域能够形成此类孔。还已知病毒表达的膜融合蛋白的某些易位结构域能够形成此类孔。此类结构域可用于本发明。
易位结构域可具有梭菌来源，例如HN结构域(或其功能性组分)。HN指梭菌神经毒素H-链中大约等于H-链氨基末端半侧的部分或片段，或者对应于完整H-链中该片段的结构域。H-链缺乏H-链的Hc组分的天然结合功能。就这方面而言，HC功能可以通过缺失HC氨基酸序列(在DNA合成水平，或者在通过核酶或蛋白酶处理的合成后水平)来去除。可选地，HC功能可以通过化学或生物处理来失活。因此，H-链不能结合天然梭菌神经毒素(即，全毒素)与之结合的靶细胞上的结合位点。
适合的(参考)易位结构域的实例包括：
上述参考序列应该认为是指导，因为可根据亚血清型而发生略微变化。作为实例，US 2007/0166332(在此通过引用并入)引用了略微不同的梭菌序列：
在本发明上下文中，包含易位结构域的多种梭菌毒素HN区可用于本发明的方面，条件是这些活性片段可以促进非细胞毒性蛋白酶(例如，梭菌L-链)从细胞内囊泡释放进入靶细胞的胞质中，并因此参与执行梭菌毒素蛋白水解切割底物的总体细胞机制。来自梭菌毒素重链的HN区的长度为大约410-430个氨基酸，并且包括易位结构域。研究显示来自梭菌毒素重链HN区的全长不是易位结构域易位活性所必需的。因此，该实施方案的方面可以包括含有长度例如至少350个氨基酸、至少375个氨基酸、至少400个氨基酸、至少425个氨基酸和至少450个氨基酸的易位结构域的梭菌毒素HN区。该实施方案的其他方面可以包括含有长度例如至多350个氨基酸、至多375个氨基酸、至多400个氨基酸和至多425个氨基酸的易位结构域的梭菌毒素HN区。
有关在肉毒梭菌和破伤风梭菌中产生毒素的遗传基础的进一步细节，我们参考Henderson等(1997)The Clostridia:Molecular Biology and Pathogenesis(梭菌：分子生物学和发病学),Academic press。
术语HN包括天然存在的神经毒素HN部分，和具有天然不存在的氨基酸序列和/或合成氨基酸残基的修饰的HN部分，只要修饰的HN部分依然显示上述易位功能。
可选地，易位结构域可以具有非梭菌来源。非梭菌(参考)易位结构域来源的实例包括但不限于：白喉毒素的易位结构域[O＝Keefe等,Proc.Natl.Acad.Sci.USA(1992)89,6202-6206；Silverman等,J.Biol.Chem.(1993)269,22524-22532；和London,E.(1992)Biochem.Biophys.Acta.,1112,第25-51页]，假单胞菌外毒素A型的易位结构域[Prior等Biochemistry(1992)31,3555-3559]，炭疽毒素的易位结构域[Blanke等Proc.Natl.Acad.Sci.USA(1996)93,8437-8442]，易位功能的多种融合肽或疏水肽[Plank等J.Biol.Chem.(1994)269,12918-12924；和Wagner等(1992)PNAS,89,第7934-7938页]，以及两亲肽[Murata等(1992)Biochem.,31,第1986-1992页]。易位结构域可以反映天然存在蛋白中存在的易位结构域，或者可以包括氨基酸变化，只要变化不破坏易位结构域的易位能力。
适用于本发明的病毒(参考)易位结构域的具体实例包括病毒表达的膜融合蛋白的某些易位结构域。例如，Wagner等(1992)和Murata等(1992)描述了衍生自流感病毒血凝素的N-末端区的许多融合肽和两亲肽的易位(即，膜融合和囊泡形成)功能。已知具有预期易位活性的其他病毒表达的膜融合蛋白有：塞姆利基森林病毒(Semliki Forest Virus，SFV)的融合肽的易位结构域、水泡性口膜炎病毒(VSV)糖蛋白G的易位结构域、SER病毒F蛋白的易位结构域和泡沫病毒包膜糖蛋白的易位结构域。病毒编码的Aspike蛋白在本发明上下文中具有特定应用，例如SFV的E1蛋白和VSV的G蛋白的G蛋白。
表(下文)中所列(参考)易位结构域的使用包括其序列变体的使用。变体可以包括一种或多种保守核酸取代和/或核酸缺失或插入，条件是变体具有必要的易位功能。变体还可以包括一种或多种氨基酸取代和/或氨基酸缺失或插入，只要变体具有必要的易位功能。
本发明多肽还可以包括易位促进结构域。所述结构域促进非细胞毒性蛋白酶递送入靶细胞的胞质溶胶，并描述于例如WO 08/008803和WO 08/008805，各自在此通过引用并入。
作为实例，适合的易位促进结构域包括包膜病毒融合肽结构域，例如适合的融合肽结构域包括流感病毒融合肽结构域(例如23个氨基酸的流感A病毒融合肽结构域)、甲病毒融合肽结构域(例如26个氨基酸的塞姆利基森林病毒融合肽结构域)、水泡性病毒融合肽结构域(例如21个氨基酸的水泡性口膜炎病毒融合肽结构域)、呼吸道病毒融合肽结构域(例如25个氨基酸的仙台病毒融合肽结构域)、麻疹病毒融合肽结构域(例如25个氨基酸的犬瘟热病毒融合肽结构域)、禽副粘病毒融合肽结构域(例如25个氨基酸的新城疫病毒融合肽结构域)、亨尼巴病毒融合肽结构域(例如25个氨基酸的亨德拉病毒融合肽结构域)、偏肺病毒融合肽结构域(例如25个氨基酸的人偏肺病毒融合肽结构域)或泡沫病毒融合肽结构域，例如猴泡沫病毒融合肽结构域；或其片段或变体。
作为进一步实例，易位促进结构域可以包括梭菌毒素HCN结构域或其片段或变体。更具体说，梭菌毒素HCN易位促进结构域可以具有至少200个氨基酸、至少225个氨基酸、至少250个氨基酸、至少275个氨基酸的长度。就这方面而言，梭菌毒素HCN易位促进结构域优选具有至多200个氨基酸、至多225个氨基酸、至多250个氨基酸或至多275个氨基酸的长度。具体(参考)实例包括：
上述序列位置可以根据血清型/亚型而有一点变化，并且适合(参考)梭菌毒素HCN结构域的进一步实例包括：
所有上述促进结构域可以与适用于本发明的任何前述易位结构域肽组合。因此，作为实例，非梭菌促进结构域可以与非梭菌易位结构域肽或者与梭菌易位结构域肽组合。可选地，梭菌毒素HCN易位促进结构域可以与非梭菌易位结构域肽组合。可选地，梭菌毒素HCN促进结构域可以与梭菌易位结构域肽组合，其实例包括：
序列同源性：
许多序列比对方法的任何一个可以用来确定百分比同一性，包括但不限于全体法(global methods)、局部法(local methods)和混合法(hybrid methods)，例如区段方法。确定百分比同一性的方法是本领域技术人员范围内的常规方法。全体法比对分子从始到终的序列并通过加合个体残基对的得分和通过加入空位罚分来确定最佳比对。非限制性方法包括例如CLUSTAL W，参见例如Julie D.Thompson等,CLUSTAL W:Improving theSensitivity of Progressive Multiple Sequence Alignment Through SequenceWeighting,Position-Specific Gap Penalties and Weight Matrix Choice(CLUSTAL W:通过序列加权、位置特异性空位罚分和权矩阵选择来提高渐进多序列比对的灵敏度),22(22)Nucleic Acids Research 4673-4680(1994)；和迭代改善，参见例如Osamu Gotoh,Significant Improvement in Accuracy of Multiple Protein.Sequence Alignmentsby Iterative Refinement as Assessed by Reference to Structural Alignments(通过参考结构比对评估，通过迭代改善提高多蛋白序列比对的准确性),284(4)J.Mol Biol823-838(1996)。局部法通过鉴定所有输入序列共有的一个或多个保守基序来比对序列。非限制性方法包括例如Match-box,参见例如Eric Depiereux和Ernest Feytmans,Match-Box:A Fundamentally New Algorithm for the Simultaneous Alignment of SeveralProtein Sequences(Match-Box:用于同时比对几个蛋白序列的全新算法),8(5)CABIOS501-509(1992)；Gibbs抽样，参见例如C.E.Lawrence等,Detecting Subtle SequenceSignals:A Gibbs Sampling Strategy for Multiple Alignment(检测微弱序列信号：用于多比对的Gibbs抽样策略),282(5131)Science 208-214(1993)；Align-M，参见例如IvoVan Walle等,Alin-M-A New Algorithm for Multiple Alignment of Highly DivergentSequences(Alin-M–用于高多样性序列的多比对的新算法),20(9)Bioinformatics:1428-1435(2004)。
因此，百分比序列同一性通过常规方法确定。参见例如Altschul等,Bull.Math.Bio.48:603-16,1986，以及Henikoff和Henikoff,Proc.Natl.Acad.Sci.USA 89:10915-19,1992。简言之，比对两个氨基酸序列以优化比对得分，使用空位开放罚分10、空位延伸罚分1和Henikoff和Henikoff(同上)的“blosum 62”得分矩阵，如下所示(氨基酸通过标准单字母代码表示)。
用于确定序列同一性的比对得分
然后计算百分比同一性为：
基本上同源的多肽特征为具有一个或多个氨基酸取代、缺失或添加。这些变化优选性质轻微，其是保守氨基酸取代(见下文)和不显著影响多肽折叠或活性的其他取代；小缺失，通常为1至约30个氨基酸；和小的氨基或羧基末端延伸，例如氨基末端甲硫氨酸残基，达约20-25个残基的小接头肽，或亲和标签。
保守氨基酸取代
碱性：精氨酸
赖氨酸
组氨酸
酸性：谷氨酸
天冬氨酸
极性：谷氨酰胺
天冬酰胺
疏水性：亮氨酸
异亮氨酸
缬氨酸
芳香族：苯丙氨酸
色氨酸
酪氨酸
小的：甘氨酸
丙氨酸
丝氨酸
苏氨酸
甲硫氨酸
除了20种标准氨基酸，非标准氨基酸(例如4-羟基脯氨酸、6-N-甲基赖氨酸、2-氨基异丁酸、异缬氨酸和α-甲基丝氨酸)可以取代本发明多肽的氨基酸残基。有限数目的非保守氨基酸、不是由遗传密码编码的氨基酸和非天然氨基酸可以取代梭菌多肽氨基酸残基。本发明多肽还可以包括非天然存在的氨基酸残基。
非天然存在的氨基酸包括但不限于反式-3-甲基脯氨酸、2,4-亚甲基-脯氨酸、顺式-4-羟基脯氨酸、反式-4-羟基-脯氨酸、N-甲基甘氨酸、别-苏氨酸、甲基-苏氨酸、羟基-乙基半胱氨酸、羟基乙基高半胱氨酸、硝基-谷氨酰胺、高谷氨酰胺、六氢吡啶酸、叔亮氨酸、正缬氨酸、2-氮杂苯丙氨酸、3-氮杂苯丙氨酸、4-氮杂苯丙氨酸和4-氟苯丙氨酸。用于将非天然存在的氨基酸残基加入蛋白的几种方法是本领域已知的。例如，可以采用体内系统，其中使用化学氨基酰化抑制剂tRNA抑制无义突变。用于合成氨基酸和氨基酰化tRNA的方法是本领域已知的。含有无义突变的质粒的转录和翻译在无细胞系统中进行，所述系统包括大肠杆菌S30提取物和商业上可用的酶和其他试剂。蛋白质通过色谱法纯化。参见例如Robertson等,J.Am.Chem.Soc.113:2722,1991；Ellman等,Methods Enzvmol.202:301,1991；Chung等,Science 259:806-9,1993；和Chung等,Proc.Natl.Acad.Sci.USA 90:10145-9,1993)。在第二种方法中，翻译在爪蟾卵中进行，通过显微注射突变的mRNA和化学氨基酰化的抑制剂tRNA(Turcatti等,J.Biol.Chem.271:19991-8,1996)。在第三种方法中，大肠杆菌细胞在缺乏将被替代的天然氨基酸(例如苯丙氨酸)和存在希望的非天然存在的氨基酸(例如，2-氮杂苯丙氨酸、3-氮杂苯丙氨酸、4-氮杂苯丙氨酸或4-氟苯丙氨酸)下培养。非天然存在的氨基酸被加入多肽以替代其天然对应物。参见Koide等,Biochem.33:7470-6,1994。天然存在的氨基酸残基可以通过体内化学修饰而被转化为非天然存在的种类。化学修饰可以结合定点诱变以进一步扩大取代范围(Wynn和Richards,Protein Sci.2:395-403,1993)。
有限数目的非保守氨基酸、不是由遗传密码编码的氨基酸、非天然存在的氨基酸和非天然氨基酸可以取代本发明多肽的氨基酸残基。
本发明多肽的必需氨基酸可以根据本领域已知的程序鉴定，例如位点诱变或丙氨酸扫描诱变(Cunningham和Wells,Science 244:1081-5,1989)。生物相互作用位点可以通过物理分析结构来确定，如通过诸如核磁共振、结晶学、电子衍射或光亲和标记结合推定接触位点氨基酸的突变所确定的。参见例如de Vos等,Science 255:306-12,1992；Smith等.J.Mol.Biol.224:899-904,1992；Wlodaver等,FEBS Lett.309:59-64,1992。必需氨基酸的身份可以通过分析与本发明多肽相关组分(例如易位组分或蛋白酶组分)的同源性来推断。
可以使用已知的诱变和筛选方法来进行和测试多个氨基酸取代，例如Reidhaar-Olson和Sauer(Science 241:53-7,1988)或Bowie和Sauer(Proc.Natl.Acad.Sci.USA 86:2152-6,1989)所公开的那些。简言之，这些作者公开了同时随机化多肽中两个或多个位置、选择功能性多肽、然后测序突变多肽以确定每个位置可允许取代的谱的方法。可以使用的其他方法包括噬菌体展示(例如,Lowman等,Biochem.30:10832-7,1991；Ladner等,美国专利号5,223,409；Huse,WIPO公布WO 92/06204)和区域定向诱变(Derbyshire等,Gene 46:145,1986；Ner等,DNA 7:127,1988)。
可以使用已知的诱变和筛选方法来进行和测试多个氨基酸取代，例如Reidhaar-Olson和Sauer(Science 241:53-7,1988)或Bowie和Sauer(Proc.Natl.Acad.Sci.USA 86:2152-6,1989)所公开的那些。简言之，这些作者公开了同时随机化多肽中两个或多个位置、选择功能性多肽、然后测序突变多肽以确定每个位置可允许取代的谱的方法。可以使用的其他方法包括噬菌体展示(例如,Lowman等,Biochem.30:10832-7,1991；Ladner等,美国专利号5,223,409；Huse,WIPO公布WO 92/06204)和区域定向诱变(Derbyshire等,Gene 46:145,1986；Ner等,DNA 7:127,1988)。
下面是附图简述，其描述了本发明的方面和/或实施方案。
图1-LHN/C-大鼠GHRP融合蛋白的纯化
使用实施例3所述方法，从大肠杆菌BL21(DE3)细胞纯化了LHN/C-rGHRP融合蛋白。简言之，在细胞破碎后获得的可溶性产物被施加至充镍亲和捕获柱。结合蛋白用200mM咪唑洗脱，用Xa因子处理以活化融合蛋白，然后再施加至第二个充镍亲和捕获柱。来自纯化程序的样品通过SDS-PAGE评估。泳道1：分子量标准(kDa)，泳道2：澄清的粗制细胞裂解液，泳道3-5：第一个镍螯合琼脂糖柱洗脱液(0.1mg/ml)，泳道6-8：第一个镍螯合琼脂糖柱洗脱液(0.01mg/ml)，泳道9：在非还原条件下Xa因子消化的蛋白，泳道10：在非还原条件下纯化的LHN/C-rGHRP，泳道11：在还原条件下纯化的LHN/C-rGHRP。
图2–LHN/C-大鼠LEP116-122融合蛋白的纯化
使用实施例3所述方法，从大肠杆菌BL21(DE3)细胞纯化了LHN/C-大鼠LEP116-122融合蛋白。简言之，在细胞破碎后获得的可溶性产物被施加至充镍亲和捕获柱。结合蛋白用200mM咪唑洗脱，用Xa因子处理以活化融合蛋白，然后再施加至第二个充镍亲和捕获柱。来自纯化程序的样品通过SDS-PAGE评估。泳道1：第一个镍螯合琼脂糖柱洗脱液，泳道2：在非还原条件下用Xa因子处理的第一个镍螯合琼脂糖柱洗脱液，泳道3：在还原条件下用Xa因子处理的第一个镍螯合琼脂糖柱洗脱液，泳道4-6：在非还原条件下的第二个镍螯合琼脂糖柱洗脱液，泳道7-9：在还原条件下的第二个镍螯合琼脂糖柱洗脱液，泳道10：分子量标准(kDa)，
图3–从用各种LHn处理的分化MtT/S分泌GH
使用实验数据部分所述的方法：在用10-8M皮质酮分化MtT/S细胞之后，细胞在48小时期间用下述分子之一处理：LHnB(100nM)、LHnC(100nM)或LHnD(100nM)。然后使细胞经受分泌测定10分钟，使用含有40mM KCl的Krebs培养基。
图4-LHN/A-GHRH融合蛋白的纯化
使用实施例3所述方法，从大肠杆菌BL21(DE3)细胞纯化了LHN/A-GHRH融合蛋白。简言之，在细胞破碎后获得的可溶性产物被施加至充镍亲和捕获柱。结合蛋白用200mM咪唑洗脱，用Xa因子处理以活化融合蛋白，然后再施加至第二个充镍亲和捕获柱。来自纯化程序的样品通过SDS-PAGE评估。泳道1：分子量标准(kDa)，泳道2：可溶性级分；泳道3：在非还原条件下用Xa因子处理的第一个镍螯合琼脂糖柱洗脱液，泳道4：在非还原条件下的第二个镍螯合琼脂糖柱负荷，泳道5：在非还原条件下的第二个镍螯合琼脂糖柱洗脱液，泳道6：在非还原条件下的最终样品，泳道7：在还原条件下的最终样品。
图5–LHN/C-GHRH融合蛋白的纯化
使用实施例3所述方法，从大肠杆菌BL21(DE3)细胞纯化了LHN/A-GHRH融合蛋白。简言之，在细胞破碎后获得的可溶性产物被施加至充镍亲和捕获柱。结合蛋白用200mM咪唑洗脱，用Xa因子处理以活化融合蛋白，然后再施加至第二个充镍亲和捕获柱。来自纯化程序的样品通过SDS-PAGE评估。泳道1：分子量标准(kDa)，泳道2：可溶性级分，泳道3：在非还原条件下用Xa因子处理的第一个镍螯合琼脂糖柱洗脱液，泳道4：在非还原条件下的第二个镍螯合琼脂糖柱负荷，泳道5：在非还原条件下的第二个镍螯合琼脂糖柱洗脱液，泳道6：在非还原条件下的最终样品，泳道7：在还原条件下的最终样品。
图6-LHN/A-GHRH和LHN/C-GHRH最终产品。
使用实施例3所述方法，从大肠杆菌BL21(DE3)细胞纯化了LHN/A-GHRH和LHN/C-GHRH融合蛋白。来自纯化程序的样品通过SDS-PAGE评估。泳道1：分子量标准(kDa)，泳道2：非还原条件下的最终样品(LHN/A-GHRH)，泳道3：还原条件下的最终样品(LHN/A-GHRH)，泳道4：在非还原条件下的最终样品(LHN/C-GHRH)，泳道5：在还原条件下的最终样品(LHN/C-GHRH)。
图7-CP-GHRH-LHD在体内对大鼠IGF-1水平的活性
图7显示与仅媒介物对照相比较，i.v.施用CP-GHRH-LHD(SXN101000)在处理后5天对大鼠IGF-1水平的影响。
图8-CP-GHRH-LHD在体内对大鼠IGF-1水平的活性
图8显示与仅媒介物对照相比较，i.v.施用CP-GHRH-LHD(SXN101000)在处理后第1至8天对大鼠IGF-1水平的影响。由于第9和10天插管堵塞，n数目太少以致于不能考虑。
图9–CP-GHRH-LHD在体内对大鼠GH水平的活性
图9b显示与仅媒介物对照(图9a)和奥曲肽输注(图9c)相比较，i.v.施用CP-GHRH-LHD(SXN101000)在处理后5天对大鼠GH水平的影响。
实施例
实施例1LHN/C主链构建体的制备
实施例2LHN/C-人GHRP的构建
实施例3LHN/C-人GHRP融合体的表达和纯化
实施例4LHN/D-CP-qGHRH29融合蛋白的构建
实施例5LHN/D-CP-qGHRH29融合蛋白的表达和纯化
实施例6LHN/A与SST TM的化学轭合
实施例7用于治疗结肠直肠癌的方法
实施例8用于治疗乳腺癌的方法
实施例9用于治疗前列腺癌的方法
实施例10用于治疗肺癌的方法
实施例11用于治疗结肠直肠癌的方法
实施例12用于治疗小细胞肺癌的方法
实施例13用于治疗前列腺癌的方法
实施例14用于治疗小细胞肺癌的方法
实施例15用于治疗乳腺癌的方法
实施例16用于治疗结肠直肠癌的方法
实施例17用于治疗前列腺癌的方法
实施例18用于治疗小细胞肺癌的方法
实施例19用于治疗结肠直肠癌的方法
实施例20用于治疗乳腺癌的方法
实施例21用于治疗结肠直肠癌的方法
实施例22用于治疗前列腺癌的方法
实施例23用于治疗乳腺癌的方法
实施例24用于治疗小细胞肺癌的方法
实施例25用于治疗结肠直肠癌的方法
实施例26用于治疗前列腺癌的方法
实施例27用于治疗乳腺癌的方法
实施例28用于治疗小细胞肺癌的方法
实施例29结合、分泌和体内测定
实施例30-用于治疗非小细胞肺癌的方法
实施例31-用于治疗非小细胞肺癌的方法
实施例32-用于治疗非小细胞肺癌的方法
实施例33-用于治疗乳腺癌的方法
实施例34-用于治疗小细胞肺癌的方法
实施例35-用于治疗结肠直肠癌的方法
实施例36-用于治疗前列腺癌的方法
实施例37CP-GHRH-LHD在体内对大鼠IGF-1水平的活性
实施例38CP-GHRH-LHD在体内对大鼠IGF-1水平的活性
实施例39CP-GHRH-LHD在体内对大鼠生长激素水平的活性
SEQ ID NO
当起始Met氨基酸残基或相应的起始密码子在下述SEQ ID NO的任一个中指明时，所述残基/密码子是任选的。
SEQ ID1 LHN/A的DNA序列
SEQ ID2 LHN/B的DNA序列
SEQ ID3 LHN/C的DNA序列
SEQ ID4 LHN/D的DNA序列
SEQ ID5 IgA-HNtet的DNA序列
SEQ ID6 人GHRP接头的DNA序列
SEQ ID7 人GHRP-C融合体的DNA序列
SEQ ID8 人GHRP-C融合体的蛋白序列
SEQ ID9 人GHRH-D融合体的蛋白序列
SEQ ID10 人EGF-D融合体的蛋白序列
SEQ ID11 人NGF-D GS35融合体的蛋白序列
SEQ ID12 人LEP116-122-D融合体的蛋白序列
SEQ ID13 人VIP-D融合体的蛋白序列
SEQ ID14 人LEP116-122-C融合体的蛋白序列
SEQ ID15 人IGF1-C融合体的蛋白序列
SEQ ID16 人SST14-C GS35融合体的蛋白序列
SEQ ID17 人GHRP-D融合体的蛋白序列
SEQ ID18 人IGF1-D融合体的蛋白序列
SEQ ID19 人NGF-C融合体的蛋白序列
SEQ ID20 人SST14-D GS20融合体的蛋白序列
SEQ ID21 人VIP-C融合体的蛋白序列
SEQ ID22 人生长素释放肽-A融合体的蛋白序列
SEQ ID23 CP-hGHRH29N8A K12N M27L-LHD融合体的蛋白序列
SEQ ID24 N-末端-hGHRH29N8A M27L-LHD融合体的蛋白序列
SEQ ID25 IgA-HNtet-SST14融合体的蛋白序列
SEQ ID26 IgA-HNtet-GHRP融合体的蛋白序列
SEQ ID27 人生长素释放肽S3W-A融合体的蛋白序列
SEQ ID28 SST28-D融合体的蛋白序列
SEQ ID29 GRP-D融合体的蛋白序列
SEQ ID30 GRP-B融合体的蛋白序列
SEQ ID31 CP-qGHRH29接头的DNA序列
SEQ ID32 CP-qGHRH29-D融合体的DNA序列
SEQ ID33 CP-qGHRH29-D融合体的蛋白序列
SEQ ID34 CP-qGHRH-A融合体的蛋白序列
SEQ ID35 CP-qGHRH-C融合体的蛋白序列
SEQ ID36 CP-qGHRH-D融合体的蛋白序列
SEQ ID37 CP-qGHRH-D N10-PL5融合体的蛋白序列
SEQ ID38 CP-qGHRH-D N10-HX12融合体的蛋白序列
SEQ ID39 CP-SST28-D融合体的蛋白序列
SEQ ID40 CP-SST14-D融合体的蛋白序列
SEQ ID41 IgA-CP-SST14-HNtet融合体的蛋白序列
SEQ ID42 CP-UTS-A融合体的蛋白序列
SEQ ID43 CP-hTGF-B GS10-NS融合体的蛋白序列
SEQ ID44 CP-hTGF-B GS10-GS20融合体的蛋白序列
SEQ ID45 LHN/A的蛋白序列
SEQ ID46 LHN/B的蛋白序列
SEQ ID47 LHN/C的蛋白序列
SEQ ID48 LHN/D的蛋白序列
SEQ ID49 IgA-HNtet的蛋白序列
SEQ ID50 合成的奥曲肽
SEQ ID51 合成的GHRH激动剂肽
SEQ ID52 合成的GHRH拮抗剂肽
SEQ ID53 CP-MCH-D融合体的蛋白序列
SEQ ID54 KISS-D融合体的蛋白序列
SEQ ID55 PrRP-A融合体的蛋白序列
SEQ ID56 CP-CRH-C融合体的蛋白序列
SEQ ID57 CP-HS_GHRH_1-27-LHD融合体的蛋白序列
SEQ ID58 CP-HS_GHRH_1-28-LHD融合体的蛋白序列
SEQ ID59 CP-HS_GHRH_1-29-LHD融合体的蛋白序列
SEQ ID60 CP-HS_GHRH_1-44-LHD融合体的蛋白序列
SEQ ID61 CP-HS_GHRH_1-40-LHD融合体的蛋白序列
SEQ ID62 CP-HS_GHRH_Ala9-LHD融合体的蛋白序列
SEQ ID63 CP-HS_GHRH_Ala22-LHD融合体的蛋白序列
SEQ ID64 CP-HS_GHRH_Ala8_Lys11_1-29-LHD融合体的蛋白序列
SEQ ID65 蛋白CP-HS_GHRH_Ala8_Lys11_Arg12_1-29-LHD融合体
SEQ ID66 CP-HS_GHRH_Ala8_Asn11_1-29-LHD融合体的蛋白序列
SEQ ID67 CP-HS_GHRH_Ala8_Lys20_1-29-LHD融合体的蛋白序列
SEQ ID68 蛋白CP-HS_GHRH_Ala8_Lys11_Lys20_1-29-LHD融合体
SEQ ID69 CP-HS_GHRH_Ala8_Asn20_1-29-LHD融合体的蛋白序列
SEQ ID70 CP-HS_GHRH_Ala8_Asn12_1-29-LHD融合体的蛋白序列
SEQ ID71 CP-HS_GHRH_Ala8_Asn21_1-29-LHD融合体的蛋白序列
SEQ ID72 CP-HS_GHRH_Ala8_Glu_7_1-29-LHD融合体的蛋白序列
SEQ ID73 CP-HS_GHRH_Ala8_Glu_10_1-29LHD融合体的蛋白序列
SEQ ID74 蛋白CP-HS_GHRH_Ala8_Glu_13_1-29-LHD融合体
SEQ ID75 CP-HS_GHRH_Ala8-LHD融合体的蛋白序列
SEQ ID76 CP-HS_GHRH_Glu8_1-29-LHD融合体的蛋白序列
SEQ ID77 CP-HS_GHRH_Ala15_1-27-LHD融合体的蛋白序列
SEQ ID78 CP-HS_GHRH_Ala15-LHD融合体的蛋白序列
SEQ ID79 CP-HS_GHRH_Ala8_Ala15_1-29-LHD融合体的蛋白序列
SEQ ID80 蛋白CP-HS_GHRH_Ala8_9_15_22_27-LHD融合体
SEQ ID81 CP-HS_GHRH_Ala8_9_15_22-LHD融合体的蛋白序列
SEQ ID82 CP-HS_GHRH_HVQAL_1-32-LHD融合体的蛋白序列
SEQ ID83 CP-HS_GHRH_HVSAL_1-29-LHD融合体的蛋白序列
SEQ ID84 CP-HS_GHRH_HVTAL_1-29-LHD融合体的蛋白序列
SEQ ID85 CP-HS_GHRH_QALN-LHD融合体的蛋白序列
SEQ ID86 CP-HS_GHRH_QAL-LHD融合体的蛋白序列
SEQ ID87 CP-hGHRH29N8A M27L-LHD融合体的蛋白序列
实施例1-LHN/C主链构建体的制备
下述程序产生用作多结构域融合表达的表达主链的克隆。该实施例基于制备基于血清型C的克隆(SEQ ID3)，但是程序和方法同样适用于所有LHN血清型，例如血清型A、B和D(SEQ ID1、2和4)以及其他蛋白酶或易位结构域，例如IgA和破伤风HN(SEQ ID 5)，通过使用适当公开的用于合成的序列或者在通过PCR扩增产生时的DNA模板(SEQ ID5)。
克隆和表达载体的制备
pCR 4(Invitrogen)是选定的标准克隆载体，其被选择是因为载体内缺乏限制序列和相邻测序引物位点以方便确认构建体。表达载体是基于pET(Novagen)表达载体，其已经被修饰为含有用于构建体插入的多克隆位点NdeI-BamHI-SalI-PstI-XbaI-HindIII，表达载体片段已经被去除以产生非迁移性质粒，多个不同融合标签已经被插入以增加纯化选择，并且载体主链中已有的XbaI位点已经被去除以简化亚克隆。
LC/C的制备
通过LC/C氨基酸序列(获自免费可用的数据库来源，例如GenBank(登录号P18640)，使用多种反向翻译软件工具之一(例如回译工具v2.0(Entelechon))的回译来设计DNA序列。BamHI/SalI识别序列被分别加入序列的5'和3'末端，保持正确的阅读框。筛选DNA序列(使用诸如SeqBuilder,DNASTAR Inc.的软件)在回译过程中加入的限制酶切割序列。通过回译工具从提出的编码序列去除被发现与克隆系统所需的那些序列共同的任何切割序列，保证维持常见的大肠杆菌密码子选择。大肠杆菌密码子选择通过参考软件程序例如Graphical Codon Usage Analyser(Geneart)来评估，并且％GC含量和密码子选择比率参考公开的密码子选择表(例如GenBank Release 143,2004年9月13日)来评估。然后，含有LC/C开放阅读框(ORF)的该优化的DNA序列被商业合成(例如由Entelechon、Geneart或Sigma-Genosys)并且提供于pCR 4载体中。
HN/C插入物的制备
通过HN/C氨基酸序列(获自免费可用的数据库来源，例如GenBank(登录号P18640)，使用多种反向翻译软件工具之一(例如回译工具v2.0(Entelechon))的回译来设计DNA序列。PstI限制序列被添加至N末端，并且XbaI-终止密码子-HindIII被添加至C末端，保证维持正确的阅读框。筛选DNA序列(使用诸如SeqBuilder、DNASTAR Inc.的软件)在回译过程中加入的限制酶切割序列。通过回译工具从提出的编码序列去除被发现与克隆系统所需的那些序列共同的任何序列，保证维持常见的大肠杆菌密码子选择。大肠杆菌密码子选择通过参考软件程序例如Graphical Codon Usage Analyser(Geneart)来评估，并且％GC含量和密码子选择比率参考公开的密码子选择表(例如GenBank Release 143,2004年9月13日)来评估。然后，该优化的DNA序列被商业合成(例如由Entelechon、Geneart或Sigma-Genosys)并且提供于pCR 4载体中。
间隔物(LC-HN接头)的制备
LC-HN接头可以根据第一原理设计，使用现有的接头序列信息作为模板。例如，血清型C接头(此时被定义为在LC和HN之间二硫桥的半胱氨酸之间存在的结构域间多肽区)具有序列HKAIDGRSLYNKTLD，含有天然的Xa因子切割位点。该序列信息可免费获自可用数据库来源，例如GenBank(登录号P18640)或Swissprot(登录位置BXC1_CLOBO)。为了产生特异性蛋白酶切割位点，Xa因子的天然识别序列可用于修饰的序列VDAIDGRSLYNKTLQ，或者肠激酶活化位点可以被插入活化环以产生诸如VDGIITSKTKSDDDDKNKALNLQ的序列。使用多种反向翻译软件工具之一(例如EditSeq best大肠杆菌反向翻译(DNASTAR Inc.)或回译工具v2.0(Entelechon))，确定编码接头区的DNA序列。BamHI/SalI和PstI/XbaI/终止密码子/HindIII限制酶序列以正确的阅读框被加入每个末端。筛选DNA序列(使用诸如MapDraw,DNASTAR Inc.的软件)在回译过程中加入的限制酶切割序列。从提出的编码序列手工去除被发现与克隆系统所需的那些序列共同的任何序列，保证维持常见的大肠杆菌密码子选择。大肠杆菌密码子选择通过参考软件程序例如Graphical Codon Usage Analyser(Geneart)来评估，并且％GC含量和密码子选择比率参考公开的密码子选择表(例如GenBank Release 143,2004年9月13日)来评估。然后，该优化的DNA序列被商业合成(例如由Entelechon、Geneart或Sigma-Genosys)并且提供于pCR 4载体中。
主链克隆的组装和确认
由于尺寸小，活化接头必须使用两步过程来转移。pCR-4接头载体用BamHI+SalI组合限制酶切割，然后切割的接头载体用作BamHI+SalI组合限制酶切割的LC DNA的接受者。一旦LC编码DNA被插入接头DNA的上游，则完整的LC-接头DNA片段可以被分离并转移至pET表达载体MCS。使用BamHI/PstI限制酶消化从pCR 4克隆载体切除LC-接头。pET表达载体用相同的酶消化，但还用热敏磷酸酶(antarctic phosphatase)处理作为预防再环化的额外措施。LC-接头和pET载体主链被凝胶纯化，并且纯化的插入物和载体主链使用T4DNA连接酶连接在一起。产物转化用TOP10细胞，然后使用BamHI/PstI限制消化来筛选LC-接头。然后重复该过程，以将HN插入pET-LC-接头构建体的PstI/HindIII限制位点。
使用限制酶的筛选足以保证最终主链是正确的，因为所有组分已经在合成过程中被测序确认。然而，在一些组分亚克隆入主链时，如果类似大小的片段被去除和插入，需要测序小区域以确认正确的插入。
实施例2-LHN/C-人GHRP的构建
下述程序产生用作多结构域融合表达的表达构建体的克隆，其中靶向部分(TM)出现在易位结构域的C-末端。该实施例基于人GHRP-C融合体(SEQ ID7)的制备，但是程序和方法同样适用于产生其他蛋白酶、易位和TM融合体，其中TM在易位结构域的C-末端。
间隔物-人GHRP插入物的制备
为了使GHRP序列出现在HN结构域的C-末端，DNA序列被设计为在间隔物和靶向部分(TM)区域的侧翼，允许加入主链克隆(SEQ ID3)。DNA序列可以被排列为BamHI-SalI-PstI-XbaI-间隔物-GHRP-终止密码子-HindIII(SEQ ID6)。可以使用多种反向翻译软件工具之一(例如EditSeq best大肠杆菌反向翻译(DNASTAR Inc.)或回译工具v2.0(Entelechon))设计DNA序列。一旦设计好TM DNA，编码优选间隔物所需的其他DNA通过计算机模拟(in silico)产生。优选保证：维持间隔物、GHRP和限制序列的正确阅读框，并且XbaI序列之前不是碱基TC，碱基TC会导致DAM甲基化。筛选DNA序列中加入的限制序列，并且从其余序列手工去除任何额外序列，保证维持常见的大肠杆菌密码子选择。大肠杆菌密码子选择通过参考软件程序例如Graphical Codon Usage Analyser(Geneart)来评估，并且％GC含量和密码子选择比率参考公开的密码子选择表(例如GenBank Release 143,2004年9月13日)来评估。然后，该优化的DNA序列被商业合成(例如由Entelechon、Geneart或Sigma-Genosys)并且提供于pCR 4载体中。
间隔物-人GHRP插入主链
为了使用主链构建体(SEQ ID3)和编码GHRP TM(SEQ ID6)的新合成的pCR 4-间隔物-TM载体产生LC-接头-HN-间隔物-GHRP构建体(SEQ ID7)，可以使用一步或两步方法；通常，当TM DNA小于100个碱基对时使用两步方法。使用一步方法，通过用XbaI和HindIII限制酶切割pCR4-间隔物-TM载体并将TM编码DNA片段插入类似切割的pET主链构建体，GHRP可以被直接插入主链构建体。使用两步方法，LHN结构域被使用限制酶BamHI和XbaI从主链克隆切除并连接入类似消化的pCR 4-间隔物-GHRP载体。这产生了pCR 4中的LHN-间隔物-GHRPORF，其可以使用限制酶BamHI和HindIII从载体切除，用于随后连接入类似切割的pET表达构建体。最终产物含有LC-接头-HN-间隔物-GHRP DNA(SEQ ID7)，其得到含有SEQ ID8所示序列的融合蛋白。
使用限制酶的筛选足以保证最终主链是正确的，因为所有组分已经在合成过程中或PCR扩增后被测序确认。然而，在一些组分亚克隆入主链时，如果类似尺寸的片段被去除和插入，需要测序小区域以确认正确的插入。
实施例3-LHN/C-人GHRP融合体的表达和纯化
该实施例基于含有SEQ ID8所示序列的人GHRP-C融合体的制备，其中pET表达载体ORF还编码组氨酸纯化标签。这些程序和方法同样适用于本发明的任何C-末端存在的融合蛋白。适当时，活化酶应该被选择与每个序列中的蛋白酶活化位点相容。
LHN/C-GHRP融合蛋白的表达
LHN/C-GHRP融合蛋白的表达使用下述方案来实现。孵育在250ml烧瓶中含有0.2％葡糖胺和30μg/ml卡那霉素的100ml改良TB与来自LHN/C-GHRP表达菌株的单菌落。培养物在37℃、225rpm下生长16小时。孵育在2L烧瓶中含有0.2％葡糖胺和30μg/ml卡那霉素的1L改良TB与10ml过夜培养物。培养物在37℃生长，直至达到大约0.5的OD600nm，此时降低温度至16℃。1小时后，培养物用1mM IPTG诱导并在16℃下生长另外16小时。
LHN/C-GHRP融合蛋白的纯化
Defrost falcon管含有35ml 50mM HEPES pH 7.2 200mM NaCl和大约10g大肠杆菌BL21(DE3)细胞糊。以30秒开、30秒关的10个循环、功率为22微米在冰上声处理细胞糊，保证样品维持冷却。裂解的细胞在18 000rpm,4℃旋转离心30分钟。使上清液加至用50mMHEPES pH 7.2200mM NaCl平衡的荷0.1M NiSO4螯合柱(20-30ml柱足够)。使用40和100mM咪唑的不连续梯度，洗掉非特异性结合的蛋白并用200mM咪唑洗脱融合蛋白。洗脱的融合蛋白用5L 50mM HEPES pH 7.2 200mM NaCl在4℃透析过夜并测量透析的融合蛋白的OD。每1mg融合蛋白添加10mg Xa因子并在25℃静态孵育过夜。加至用50mM HEPES pH 7.2200mM NaCl平衡的荷0.1M NiSO4螯合柱(20-30ml柱足够)。用50mM HEPES pH 7.2 200mM NaCl洗涤柱至基线。使用40和100mM咪唑的不连续梯度，洗掉非特异性结合的蛋白并用200mM咪唑洗脱融合蛋白。洗脱的融合蛋白用5L 50mM HEPES pH 7.2 150mM NaCl在4℃透析过夜并浓缩融合体至约2mg/ml，将样品分成小份并在-20℃冷冻。使用OD、BCA和纯度分析测试纯化的蛋白。图1显示通过SDS-PAGE分析的纯化蛋白，并且图2、4、5和6显示使用该方法的其他纯化构建体。
实施例4-LHN/D-CP-qGHRH29融合蛋白的构建
下述程序产生用作多结构域融合表达的表达构建体的克隆，其中靶向部分(TM)出现在蛋白酶和易位结构域的中间。该实施例基于CP-qGHRH29-D融合体(SEQ ID33)的制备，但是程序和方法同样适用于产生本发明的任何其他CP融合体。
CP-qGHRH29接头插入物的制备
为了使qGHRH29序列出现在HN结构域的N-末端，DNA序列被设计为在具有活化蛋白酶位点的TM和间隔区的侧翼，允许加入主链克隆(SEQ ID4)。DNA序列可以被排列为BamHI-SalI-间隔物-蛋白酶活化位点-qGHRH29-间隔物-PstI-XbaI-终止密码子-HindIII(SEQID31)。可以使用多种反向翻译软件工具之一(例如EditSeq best大肠杆菌反向翻译(DNASTAR Inc.)或回译工具v2.0(Entelechon))设计DNA序列。一旦设计好TM DNA，编码优选间隔物所需的其他DNA通过计算机模拟产生。优选保证：维持间隔物、蛋白酶活化位点、qGHRH29和限制序列的正确阅读框，并且XbaI序列之前不是碱基TC，碱基TC会导致DAM甲基化。筛选DNA序列中加入的限制序列，并且从其余序列手工去除任何额外序列，保证维持常见的大肠杆菌密码子选择。大肠杆菌密码子选择通过参考软件程序例如Graphical CodonUsage Analyser(Geneart)来评估，并且％GC含量和密码子选择比率参考公开的密码子选择表(例如GenBank Release 143,2004年9月13日)来评估。然后，该优化的DNA序列被商业合成(例如由Entelechon、Geneart或Sigma-Genosys)并且提供于pCR 4载体中。
CP-qGHRH29接头插入主链
为了使用主链构建体(SEQ ID4)和编码人qGHRH29 TM(SEQ ID31)的新合成的pCR4-间隔物-活化位点-TM-间隔物载体产生LC-间隔物-活化位点-qGHRH29-间隔物-HN构建体(SEQ ID32)，可以使用一步或两步方法；通常，当TM DNA小于100个碱基对时使用两步方法。使用一步方法，通过用SalI和PstI限制酶切割pCR 4-间隔物-活化位点-TM-间隔物载体并将TM编码DNA片段插入类似切割的pET主链构建体，qGHRH29接头区可以被直接插入主链构建体。使用两步方法，LC结构域被使用限制酶BamHI和SalI从主链克隆切除并连接入类似消化的pCR 4-间隔物-活化位点-TM-间隔物载体。这产生了pCR 4中的LC-间隔物-活化位点-qGHRH29-间隔物ORF，其可以使用限制酶BamHI和PstI从载体切除，用于随后连接入类似的pET表达构建体。最终产物含有LC-间隔物-活化位点-qGHRH29-间隔物-HN DNA(SEQ ID32)，其得到含有SEQ ID33所示序列的融合蛋白。
使用限制酶的筛选足以保证最终主链是正确的，因为所有组分已经在合成过程中或PCR扩增后被测序确认。然而，在一些组分亚克隆入主链时，如果类似尺寸的片段被去除和插入，需要测序小区域以确认正确的插入。
实施例5-LHN/D-CP-qGHRH29融合蛋白的表达/纯化
该实施例基于LHN/D-CP-qGHRH29融合体的制备，所述融合体含有SEQ ID33所示序列，其中pET表达载体ORF还编码组氨酸纯化标签。这些程序和方法同样适用于本发明的任何CP融合蛋白。适当时，活化酶应该被选择与每个序列内的蛋白酶活化位点是相容的。
LHN/D-CP-qGHRH29融合蛋白的表达
LHN/D-CP-qGHRH29融合蛋白的表达使用下述方案来实现。孵育在250ml烧瓶中含有0.2％葡糖胺和30μg/ml卡那霉素的100ml改良TB与来自LHN/D-CP-qGHRH29表达菌株的单菌落。使培养物在37℃、225rpm下生长16小时。孵育在2L烧瓶中含有0.2％葡糖胺和30μg/ml卡那霉素的1L改良TB与10ml过夜培养物。培养物在37℃生长，直至达到大约0.5的OD600nm，此时降低温度至16℃。1小时后，培养物用1mM IPTG诱导并在16℃下生长另外16小时。
LHN/D-CP-qGHRH29融合蛋白的纯化
Defrost falcon管含有35ml 50mM HEPES pH 7.2 200mM NaCl和大约10g大肠杆菌BL21(DE3)细胞糊。以30秒开、30秒关的10个循环、功率为22微米在冰上声处理细胞糊，保证样品维持冷却。裂解的细胞在18 000rpm、4℃旋转离心30分钟。使上清液加至用50mMHEPES pH 7.2200mM NaCl平衡的荷0.1M NiSO4螯合柱(20-30ml柱足够)。使用40和100mM咪唑的不连续梯度，洗掉非特异性结合的蛋白并用200mM咪唑洗脱融合蛋白。洗脱的融合蛋白用5L 50mM HEPES pH 7.2 200mM NaCl在4℃透析过夜并测量透析的融合蛋白的OD。每mg融合蛋白添加3.2μl肠激酶(New England Biolabs)并在25℃静态孵育过夜。加至用50mMHEPES pH 7.2 200mM NaCl平衡的荷0.1M NiSO4螯合柱(20-30ml柱足够)。用50mM HEPESpH 7.2 200mM NaCl洗涤柱至基线。使用40和100mM咪唑的不连续梯度，洗掉非特异性结合的蛋白并用200mM咪唑洗脱融合蛋白。洗脱的融合蛋白用5L 50mM HEPES pH 7.2 150mMNaCl在4℃透析过夜并浓缩融合体至约2mg/ml，将样品分成小份并在-20℃冷冻。使用OD、BCA和纯度分析测试纯化的蛋白。
实施例6-LHN/A与SST TM的化学轭合
下述程序产生化学轭合分子，其含有使用实施例3所述生产方法从SEQ ID1制备的LHN/A氨基酸序列(SEQ ID45)和化学合成的SST奥曲肽(SEQ ID50)。然而，程序和方法同样适用于本发明任何多肽的轭合制备，例如TM(例如SEQ ID51或SEQ ID52)与蛋白酶/易位融合主链(例如包含氨基酸序列SEQ ID45-49的那些)的轭合。
使用Bio-rad PD10柱将LHN/A蛋白从50mM Hepes 150mM盐缓冲液交换为PBSE(100mM 14.2g NA2HPO4,100mM 5.85g NaCl,1mM EDTANa2pH 7.5与1M HCl)。这通过用一个柱体积的PBSE洗涤PD10柱来进行，然后将蛋白加至柱，直至没有更多的滴流出PD10柱的末端。然后添加8ml PBSE并收集0.5ml级分。然后收集的级分使用A280读数测量，并且汇集含有蛋白的级分。从缓冲液交换步骤获得浓度为1.55mg/ml的LHN/A，并且这用于建立下述反应：
在流入下一个PD10柱以将缓冲液交换为PBSE之前，使样品在RT下翻转3小时，汇集含有蛋白的级分。然后将终浓度为25Mm的DTT添加至衍生的蛋白，然后使样品置于室温下10分钟。然后使用A280和A343读数算出SPDP:LHN/A相互作用比率，得到1至3的衍生化比率(derivatisation ration)的反应用于肽轭合。SPDP试剂通过N-羟基琥珀酰亚胺(NHS)酯与LHN/A的伯胺结合，使巯基反应性部分与合成肽上自由半胱氨酸上的自由SH基团形成二硫键。这种情况下，肽序列是在N末端具有自由半胱氨酸的已经被合成的奥曲肽(SEQ ID83)。SPDP-衍生的LHN/A与4倍过量的奥曲肽配体混合，然后使反应在RT下90分钟，同时翻转。然后使用PD10柱去除过量奥曲肽，留下LHN/A-奥曲肽轭合的分子。
实施例7-用于治疗结肠直肠癌的方法
被诊断有II期结肠直肠癌的59岁男性用普通化疗来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的GHRH肽TM多肽(例如SEQ ID 9、23-24、33-38、57-87)。这种情况下，多肽包括与GHRH肽化学轭合的本发明的蛋白酶易位融合主链(例如BoNT/D蛋白酶和易位结构域)。在2周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始升高时，重复治疗，在4周后，不再有使用普通检测工具(结肠镜检、CT扫描、PET扫描、等)可观察到的肿瘤，并且癌胚抗原(CEA)水平恢复正常。
实施例8-用于治疗乳腺癌的方法
被诊断有II期乳腺癌的59岁女性用普通化疗来治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的生长素释放肽TM融合蛋白(例如SEQ ID 8、17、22、26-37)。在4周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在6周后，不再有使用普通检测工具(MRI、超声、乳腺特异性正电子发射断层扫描、乳房造影术、闪烁扫描术、等)可观察到的肿瘤。
实施例9-用于治疗前列腺癌的方法
被诊断有II期前列腺癌的71岁男性用激素疗法来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的GHRH肽TM融合蛋白(例如SEQ ID 9、23-24、33-38、57-87)。在3周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，在7周后，不再有使用普通检测工具(X-射线、ProstaScint扫描、MRI、经直肠超声检查、CT扫描、等)可观察到的肿瘤，并且PSA水平恢复正常。
实施例10-用于治疗小细胞肺癌的方法
被诊断有II期小细胞肺癌的62岁女性用普通化疗来治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的IGF-1肽TM融合蛋白(例如SEQ ID 15、18)。在4周内，观察到肿瘤尺寸的显著下降，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在4周后，不再有使用普通检测工具(X-射线、CT扫描、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例11-用于治疗结肠直肠癌的方法
被诊断有II期结肠直肠癌的53岁男性用普通化疗来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的CST或SST肽TM融合蛋白(例如SEQ ID 16、20、25、28、39-41)。在2周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始升高时，重复治疗，在4周后，不再有使用普通检测工具(结肠镜检法、CT扫描、PET扫描等)可观察到的肿瘤，并且癌胚抗原(CEA)水平恢复正常。
实施例12-用于治疗小细胞肺癌的方法
被诊断有I期小细胞肺癌的59岁男性用普通化疗来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的硬骨鱼紧张肽TM融合蛋白(例如SEQ ID 42)。在3周内，观察到肿瘤尺寸的显著下降，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在5周后，不再有使用普通检测工具(X-射线、CT扫描、MRI、PET扫描、放射性核素成像、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例13-用于治疗前列腺癌的方法
被诊断有IIc期前列腺癌的66岁男性用雄激素阻断治疗来治疗。为了改善治疗效果并预防转移，他接受静脉内注射的本发明的CST或SST TM融合蛋白(例如SEQ ID 16、20、25、28、39-41)。在10天内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在2个月后，当IGF-1血液水平开始再次升高时，重复治疗，在5周后，不再有使用普通检测工具(X-射线、ProstaScint扫描、MRI、经直肠超声检查、CT扫描等)可观察到的肿瘤，并且PSA水平恢复正常。
实施例14-用于治疗小细胞肺癌的方法
被诊断为有限期小细胞肺癌的60岁女性用外科手术治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的瘦蛋白肽TM融合蛋白(例如SEQ ID 12、14)。在6周内，观察到无肿瘤再现，与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在8周后，不再有使用普通检测工具(X-射线、CT扫描、MRI、PET扫描、放射性核素成像、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例15-用于治疗乳腺癌的方法
被诊断有III期乳腺癌的62岁女性用放射来治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的VIP肽TM融合蛋白(例如SEQ ID 13、21)。在10天内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在2个月后，当IGF-1血液水平开始再次升高时，重复治疗，在3周后，不再有使用普通检测工具(MRI、超声、乳腺特异性正电子发射断层扫描、乳房造影术、闪烁扫描术等)可观察到的肿瘤。
实施例16-用于治疗结肠直肠癌的方法
被诊断有III期结肠直肠癌的50岁女性用外科手术治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的ErbB肽融合蛋白(例如SEQ ID 10)。在8周内，观察到无肿瘤再现，并且其他地方未出现转移，与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，并在8周后，不再有使用普通检测工具(结肠镜检法、CT扫描、PET扫描等)可观察到的肿瘤，并且癌胚抗原(CEA)水平保持正常。
实施例17-用于治疗前列腺癌的方法
被诊断有III期前列腺癌的67岁男性用外束照射(external beam radiation)+激素疗法来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的生长素释放肽(GHRP)肽TM融合蛋白(例如SEQ ID 8、17、22、26-37)。在3周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在7周后，不再有使用普通检测工具(X-射线、ProstaScint扫描、MRI、经直肠超声检查、CT扫描等)可观察到的肿瘤，并且PSA水平恢复正常。
实施例18-用于治疗小细胞肺癌的方法
被诊断有扩散期癌症的小细胞肺癌的65岁男性用治疗脑转移的普通化疗和放射来治疗。为了改善治疗效果并预防进一步转移，他接受静脉内注射的本发明的GHRH肽TM融合蛋白(例如SEQ ID 9、23-24、33-38、57-87)。在4周内，观察到显著的肿瘤收缩和转移消失，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，在8周后，不再有使用普通检测工具(X-射线、CT扫描、MRI、PET扫描、放射性核素成像、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例19：用于治疗结肠直肠癌的方法
被诊断有II期结肠直肠癌的66岁男性用外科手术治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的IGF-1肽TM融合蛋白(例如SEQ ID 15、18)。在接下来的三个月，观察到无肿瘤再现，而其他地方也不能检测到转移，这与IGF-1血液水平的显著下降关联。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在6个月后，没有使用普通检测工具(结肠镜检法、CT扫描、PET扫描等)可观察到的肿瘤，并且癌胚抗原(CEA)水平保持正常。
实施例20-用于治疗乳腺癌的方法
被诊断为IIIb期乳腺癌的54岁女性用新辅助化疗来治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的ErbB肽TM融合蛋白(例如SEQ ID 10)。在2周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。然后她经历改良的根治性乳房切除术并伴随重建。在3个月后，当IGF-1血液水平开始再次升高时，进行新注射，在8个月后，不再有使用普通检测工具(MRI、超声、乳腺特异性正电子发射断层扫描、乳房造影术等)可观察到的肿瘤。
实施例21-用于治疗结肠直肠癌的方法
被诊断有IV期结肠直肠癌(在肝中发现三处转移)的62岁女性用化疗治疗，通过肝动脉注射。为了改善治疗效果并预防其他地方的转移，她接受经蝶骨注射的本发明铃蟾肽(GRP)肽TM融合蛋白(例如SEQ ID 29-30)。在2周内，观察到肿瘤和转移显著收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。然后进行外科手术以同时除去肿瘤和转移。4个月后，当IGF-1血液水平开始再次升高时，重复融合蛋白治疗，在9个月后，不再有使用普通检测工具(结肠镜检法、CT扫描、PET扫描等)可观察到的肿瘤，并且癌胚抗原(CEA)水平保持正常。
实施例22-用于治疗前列腺癌的方法
被诊断有III期前列腺癌的73岁男性用激素疗法来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的VIP肽TM融合蛋白(例如SEQ ID 13、21)。在6周内，观察到肿瘤的显著收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，在5个月后，不再有使用普通检测工具(X-射线、ProstaScint扫描、MRI、经直肠超声检查、CT扫描等)可观察到的肿瘤，并且PSA水平恢复正常。
实施例23-用于治疗乳腺癌的方法
被诊断有IIIa期乳腺癌的48岁女性用新辅助化疗来治疗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的NGF肽TM融合蛋白(例如SEQ ID 11、19)。在8周内，观察到肿瘤的显著收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。然后进行根治性乳房切除术并重建。在3个月后，当IGF-1血液水平开始再次升高时，重复融合蛋白的注射，在8个月后，不再有使用普通检测工具(MRI、超声、乳腺特异性正电子发射断层扫描、乳房造影术等)可观察到的肿瘤。
实施例24-用于治疗小细胞肺癌的方法
被诊断为有限期小细胞肺癌的58岁男性用化疗加放射疗法治疗。为了改善治疗效果并预防其他地方出现转移，他接受经蝶骨注射的本发明的CST或SST肽TM融合蛋白(例如SEQ ID 16、20、25、28、39-41)。在3周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，在7个月后，不再有使用普通检测工具(X-射线、CT扫描、MRI、PET扫描、放射性核素成像、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例25-用于治疗结肠直肠癌的方法
被诊断有II结肠直肠肿瘤的75岁男性接受静脉内注射的本发明的GHRH肽TM融合蛋白(例如SEQ ID 9、23-24、33-38、57-87)。在2周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。然后患者经历外科手术以去除肿瘤。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在8个月后，不再有使用普通检测工具(结肠镜检法、CT扫描、PET扫描等)可观察到的肿瘤，并且癌胚抗原(CEA)水平保持正常。
实施例26-用于治疗前列腺癌的方法
被诊断有II期前列腺癌的66岁男性用组合的短距离放射疗法和外部束放射来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的ErbB肽TM融合蛋白(例如SEQ ID 10)。在5周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，在6个月后，不再有使用普通检测工具(X-射线、ProstaScint扫描、MRI、经直肠超声检查、CT扫描等)可观察到的肿瘤，并且PSA水平恢复正常。
实施例27-用于治疗乳腺癌的方法
被诊断为II期乳腺癌的51岁女性用下述辅助疗法来治疗：激素疗法、化疗和曲妥单抗。为了改善治疗效果并预防转移，她接受经蝶骨注射的本发明的VIP肽TM融合蛋白(例如SEQ ID 13、21)。在2周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在2个月后，当IGF-1血液水平开始再次升高时，重复治疗，在6个月后，不再有使用普通检测工具(MRI、超声、乳腺特异性正电子发射断层扫描、乳房造影术等)可观察到的肿瘤。
实施例28-用于治疗小细胞肺癌的方法
被诊断有扩散期的小细胞肺癌的56岁男性用化疗和放射疗法来治疗。为了改善治疗效果并预防其他地方的转移，他接受经蝶骨注射的本发明的生长素释放肽TM融合蛋白(例如SEQ ID 8、17、22、26-37)。在3周内，观察到肿瘤的显著收缩和转移尺寸的减小，而其他地方未出现新转移，与IGF-1血液水平的显著下降关联。在2个月和5个月后，当IGF-1血液水平开始再次升高时，重复治疗两次。患者在11个月后死亡，比对于该类型治疗和该阶段疾病所预期的晚6个月。
实施例29-结合、分泌和体内测定
为了确定多肽融合体的效力，我们证实了它们结合适当受体、降低体内和体外GH分泌和降低体内肿瘤生长的能力。下述测定针对GHRH融合蛋白示例说明。
A)结合测定：
原代垂体细胞培养物从6-8周大的雄性wistar大鼠建立。神经中间叶被切除，其余组织被切成小片并转移至分离缓冲液。然后细胞在准备测定之前在24孔板中培养48小时。
使用快速且灵敏的放射测定闪烁迫近测定(Scintillation Proximity Assay，SPA)，评估GHRH融合蛋白的结合亲和力。就这方面而言，我们在测定缓冲液中孵育大鼠GHRH膜级分与SPA珠和125I-标记的GHRH。然后进行8-点IC50替换测定，使用从10-12至10-6M不同浓度的待测试的GHRH融合蛋白。
B)分泌测定：
使用已知表达GHRH受体并分泌生长激素的MtT/S细胞，我们说明了GHRH构建体对GH分泌的潜能。使用10-8M皮质酮诱导MtT/S细胞分化48小时后，培养基被替换为含有10nMGHRH融合蛋白(LHnD和双重失活的LHnD作为对照)的培养基。48小时后，使MtT/S细胞经受分泌测定，使用10μM毛喉素(forskolin)或40mM KCl或10-8M GHRH。该类型分泌测定的实例示于图3，使用各种LHn来确定它们减少来自MtT/S细胞的生长激素的效力。
C)体内测定：
GHRH融合蛋白(图4和5)在癌的异种移植物模型中测试，使用在4-6周大的无胸腺裸(Nu/Nu)小鼠中移植的结肠直肠细胞系：Caco 2、HT 29、SW 837或SW 480。小鼠被注射0.5x107个细胞。每周两次通过数字卡尺测量肿瘤尺寸，根据椭圆形公式(短轴)2x(长轴)/2估计肿瘤体积。当异种移植物达到～70、～150或～150mm3时，则使小鼠随机接受(PBS)或GHRH融合蛋白(活性形式或双重失活形式)，并在治疗开始后4天收获肿瘤。小鼠在处死之前2小时被注射BrdU。BrdU仅掺入处于S期的分裂细胞的DNA，因此是细胞增殖的特异性标志物。通过在异氟烷麻醉下心脏穿刺而收集血液，允许在室温下凝固1小时，并在离心后收集血清，来评估IGF-1水平。根据生产商说明，通过ELISA分析IGF-1。测量并比较每组(用活性或无活性的融合蛋白治疗，或未治疗)的最终肿瘤尺寸，并与测量的IGF-1水平比较。
结论：
这些数据证实，靶向GH/IGF-1轴是治疗癌症的有效方法。通过降低GH/IGF-1的水平，可能降低IGF-1依赖性肿瘤的增殖，因此，我们可以减缓这些致死癌症的进展。
实施例30-用于治疗非小细胞肺癌的方法
被诊断有II期腺癌、非小细胞肺癌并在手术去除肿瘤后经历放疗的52岁男性非吸烟者被给予经蝶骨注射的本发明的GHRH肽TM融合蛋白(例如SEQ ID 9、23-24、3-38、57-87)。在4周内，观察到肿瘤尺寸的显著下降，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。此时中止放射疗法，肿瘤尺寸不增加，并且没有观察到转移。3个月后，当IGF-1血液水平开始再次升高时，重复融合蛋白治疗，并且肿瘤尺寸在接下来的3个月保持稳定且无转移，无需任何额外的治疗介入。
实施例31-用于治疗非小细胞肺癌的方法
被诊断有IV期未分化大细胞癌、肝和骨中具有转移、经历化疗和放疗的60岁女性吸烟者被给予经蝶骨注射的本发明的IGF-1肽TM融合蛋白(例如SEQ ID 15、18)。在4周内，有关碱性磷酸酶和丙氨酸氨基转移酶的血液测试表明骨和肝内组织损伤减少，表明转移癌减少。骨扫描也揭示骨转移减少。疾病进程被减缓，并且4个月存活患者被给予进一步的融合蛋白治疗。
实施例32-用于治疗非小细胞肺癌的方法
被诊断为在中央胸部区域的支气管中具有I期鳞状细胞癌的54岁男性吸烟者被给予经蝶骨注射的本发明的GHRH肽TM融合蛋白(例如SEQ ID 9、23-24、33-38、57-87)。在5周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。5个月后IGF-1血液水平开始再次升高时重复治疗，4个月后，不再有使用普通检测工具(X-射线、CT扫描、MRI、PET扫描、放射性核素成像、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例33-用于治疗乳腺癌的方法
被诊断为IIIa期乳腺癌的50岁女性用新辅助化疗来治疗。为了改善治疗效果并预防转移，她接受本发明的促肾上腺皮质素释放因子受体1结合肽TM融合体(例如SEQ ID56)。在8周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。然后进行根治性乳房切除术并伴随重建。在3个月后，当IGF-1血液水平开始再次升高时，重复融合蛋白的注射，在8个月后，不再有使用普通检测工具(MRI、超声、乳腺特异性正电子发射断层扫描、乳房造影术等)可观察到的肿瘤。
实施例34-用于治疗小细胞肺癌的方法
被诊断为有限期小细胞肺癌的60岁男性用化疗加放射疗法治疗。为了改善治疗效果并预防其他地方出现转移，他接受经蝶骨注射的本发明的KiSS-10或KiSS-54肽TM融合体(例如SEQ ID 54)。在3周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，并在7个月后，不再有使用普通检测工具(X-射线、CT扫描、MRI、PET扫描、放射性核素成像、支气管镜检查法等)或使用针对该癌症推荐的普通血液测试可观察到的肿瘤。
实施例35-用于治疗结肠直肠癌的方法
被诊断有II期结肠直肠肿瘤的70岁男性接受静脉内注射的本发明的黑色素浓缩激素肽TM融合体(例如SEQ ID 53)。在2周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。然后患者经历外科手术以去除肿瘤。在4个月后，当IGF-1血液水平开始再次升高时，重复治疗，在8个月后，不再有使用普通检测工具(结肠镜检法、CT扫描、PET扫描等)可观察到的肿瘤，并且癌胚抗原(CEA)水平保持正常。
实施例36-用于治疗前列腺癌的方法
被诊断有II期前列腺癌的40岁男性用组合的短距离放射疗法和外部束放射来治疗。为了改善治疗效果并预防转移，他接受经蝶骨注射的本发明的促乳素释放肽TM融合体(例如SEQ ID 55)。在5周内，观察到显著的肿瘤收缩，而其他地方未出现转移，与IGF-1血液水平的显著下降关联。在3个月后，当IGF-1血液水平开始再次升高时，重复治疗，在6个月后，不再有使用普通检测工具(X-射线、ProstaScint扫描、MRI、经直肠超声检查、CT扫描等)可观察到的肿瘤，并且PSA水平恢复正常。
实施例37CP-GHRH-LHD在体内对大鼠IGF-1水平的活性
目的–为了评估与仅媒介物治疗的对照相比，i.v.施用CP-GHRH-LHD融合体对治疗后5天大鼠中IGF-1水平的影响。
材料和方法
动物：成年雄性Sprague-Dawley大鼠保持在标准圈养条件下，05.00h开始光照(14L:10D)，自由获取食物和水，并在手术前适应圈养条件至少1周。
外科手术：在研究的第1天，大鼠(200-250g)用Hypnorm(0.32mg/kg柠檬酸芬太尼和10mg/kg氟丁酰酮，i.m.)和地西泮(2.6mg/kg i.p.)的组合麻醉。右颈内静脉被暴露，硅橡胶尖端的(silastic tipped)(i.d.0.50mm,o.d.0.93mm)聚乙烯套管(Portex,UK)被插入脉管，直至其靠近右心房入口。套管用肝素化(10IU/ml)的等渗盐水预填充。套管自由末端通过头皮切口被外置，然后穿过保护性弹簧，使用两个不锈钢螺丝和自固化牙科丙烯酸锚定至颅骨。在恢复之后，动物被圈养在自动取血室内个体笼中。保护性弹簧末端连接至机械旋转体，其允许动物最大的活动自由。套管用肝素化盐水每日冲洗以保持开放。
治疗：在研究的第2天09:00，大鼠将接受i.v.注射的CP-GHRH-LHD或仅媒介物对照。
取样：之前已经描述了自动化取血系统(ABS)(Clark等,1986；Windle等,1997)。外科手术三至四天后，每个动物的颈内静脉套管将被连接至自动取血系统。在第6天07:00，取样开始。血样使用自动化系统以10分钟间隔收集，持续24小时时段。将收集共计144个血样，每个含有不超过38μl全血。
结果
使用IGF-1ELISA试剂盒测量IGF-1水平。图7说明仅5天后，融合体治疗的大鼠中与仅媒介物对照相比IGF-1水平的统计学显著降低，t检验P值＝0.0416。
实施例38CP-GHRH-LHD在体内对大鼠IGF-1水平的活性
目的–为了考察CP-GHRH-LHD融合体的活性时程，鉴定施用与化合物对IGF-1水平的初始效应之间的时间延迟。
材料和方法：
动物：成年雄性Sprague-Dawley大鼠保持在标准圈养条件下，05.00h开始光照(14L:10D)，自由获取食物和水，并在手术前适应圈养条件至少1周。
外科手术：在研究的第1天，大鼠(260-280g)用Hypnorm和地西泮的组合麻醉。然后右颈内静脉被暴露，硅橡胶尖端的(i.d.0.50mm,o.d.0.93mm)聚乙烯套管(Portex,UK)被插入脉管，直至其靠近右侧入口。套管用肝素化(10IU/ml)的等渗盐水预填充。套管自由末端通过头皮切口被外置，然后穿过弹簧，使用不锈钢螺丝和牙科粘固剂锚定至颅骨。在恢复之后，动物被圈养在ABS室内个体笼中。弹簧连接至旋转体，其允许动物最大的活动自由。套管用肝素化盐水每日冲洗以保持开放。
治疗：在研究的第5天10:00h，大鼠将接受i.v.注射的CP-GHRH-LHD或媒介物(无菌盐水)。
血液取样：冲洗套管之后，在09.30h从每只大鼠单次人工取血样(100μl)。在实验的第5天至第18天(或直至套管堵塞)取样。来自血样的血浆被储存在-20C，用于以后通过ELISA试剂盒分析IGF-1含量。
结果
图8说明治疗后第4天，融合体治疗的大鼠中与仅媒介物对照相比IGF-1水平的统计学显著降低。
实施例39CP-GHRH-LHD在体内对大鼠生长激素水平的活性
目的–为了评估与仅媒介物治疗的对照和奥曲肽输注对照相比，i.v.施用CP-GHRH-LHD融合体对治疗后5天大鼠中生长激素水平的影响。
材料和方法
动物：成年雄性Sprague-Dawley大鼠保持在标准圈养条件下，05.00h开始光照(14L:10D)，自由获取食物和水，并在手术前适应圈养条件至少1周。
外科手术：在研究的第1天，大鼠(200-250g)用Hypnorm(0.32mg/kg柠檬酸芬太尼和10mg/kg氟丁酰酮，i.m.)和地西泮(2.6mg/kg i.p.)的组合麻醉。右颈内静脉被暴露，硅橡胶尖端的(i.d.0.50mm,o.d.0.93mm)聚乙烯套管(Portex,UK)被插入脉管，直至其靠近右心房入口。套管用肝素化(10IU/ml)的等渗盐水预填充。套管自由末端通过头皮切口被外置，然后穿过保护性弹簧，使用两个不锈钢螺丝和自固化牙科丙烯酸锚定至颅骨。在恢复之后，动物被圈养在自动取血室内个体笼中。保护性弹簧末端连接至机械旋转体，其允许动物最大的活动自由。套管用肝素化盐水每日冲洗以保持开放。
治疗：在研究的第2天09:00，大鼠将接受i.v.注射的突触融合蛋白活性化合物或媒介物。12小时输注促生长素抑制素(或类似物)将在取样开始后6小时开始(经双套管线之一施用)并将继续仅12小时。[该输注时间安排应该是良好的GH测定对照，因为我们将看到基线分泌，然后完全抑制，然后快速回复/反弹]。
取样：之前已经描述了自动化取血系统(ABS)(Clark等,1986；Windle等,1997)。外科手术三至四天后，每个动物的颈内静脉套管将被连接至自动取血系统。在第6天07:00，取样开始。血样使用自动化系统以10分钟间隔收集，持续24小时时段。将收集共计144个血样，每个含有不超过38μl全血。
结果
使用RIA测定测量生长激素水平。图9a说明媒介物治疗动物，其显示典型的生长激素脉冲释放，图9b说明用GHRH-LHD嵌合体治疗后生长激素脉冲释放的完全消除，和图9c显示生长激素脉冲释放阻断和随后在奥曲肽输注停止时恢复。
序列表
SEQ ID1 LHNA
ggatccatggagttcgttaacaaacagttcaactataaagacccagttaacggtgttgacattgcttacatcaaaatcccgaacgctggccagatgcagccggtaaaggcattcaaaatccacaacaaaatctgggttatcccggaacgtgatacctttactaacccggaagaaggtgacctgaacccgccaccggaagcgaaacaggtgccggtatcttactatgactccacctacctgtctaccgataacgaaaaggacaactacctgaaaggtgttactaaactgttcgagcgtatttactccaccgacctgggccgtatgctgctgactagcatcgttcgcggtatcccgttctggggcggttctaccatcgataccgaactgaaagtaatcgacactaactgcatcaacgttattcagccggacggttcctatcgttccgaagaactgaacctggtgatcatcggcccgtctgctgatatcatccagttcgagtgtaagagctttggtcacgaagttctgaacctcacccgtaacggctacggttccactcagtacatccgtttctctccggacttcaccttcggttttgaagaatccctggaagtagacacgaacccactgctgggcgctggtaaattcgcaactgatcctgcggttaccctggctcacgaactgattcatgcaggccaccgcctgtacggtatcgccatcaatccgaaccgtgtcttcaaagttaacaccaacgcgtattacgagatgtccggtctggaagttagcttcgaagaactgcgtacttttggcggtcacgacgctaaattcatcgactctctgcaagaaaacgagttccgtctgtactactataacaagttcaaagatatcgcatccaccctgaacaaagcgaaatccatcgtgggtaccactgcttctctccagtacatgaagaacgtttttaaagaaaaatacctgctcagcgaagacacctccggcaaattctctgtagacaagttgaaattcgataaactttacaaaatgctgactgaaatttacaccgaagacaacttcgttaagttctttaaagttctgaaccgcaaaacctatctgaacttcgacaaggcagtattcaaaatcaacatcgtgccgaaagttaactacactatctacgatggtttcaacctgcgtaacaccaacctggctgctaattttaacggccagaacacggaaatcaacaacatgaacttcacaaaactgaaaaacttcactggtctgttcgagttttacaagctgctgtgcGTCGACGGCATCATTACCTCCAAAACTAAATCTGACGATGACGATAAAAACAAAGCGCTGAACCTGCAGtgtatcaaggttaacaactgggatttattcttcagcccgagtgaagacaacttcaccaacgacctgaacaaaggtgaagaaatcacctcagatactaacatcgaagcagccgaagaaaacatctcgctggacctgatccagcagtactacctgacctttaatttcgacaacgagccggaaaacatttctatcgaaaacctgagctctgatatcatcggccagctggaactgatgccgaacatcgaacgtttcccaaacggtaaaaagtacgagctggacaaatataccatgttccactacctgcgcgcgcaggaatttgaacacggcaaatcccgtatcgcactgactaactccgttaacgaagctctgctcaacccgtcccgtgtatacaccttcttctctagcgactacgtgaaaaaggtcaacaaagcgactgaagctgcaatgttcttgggttgggttgaacagcttgtttatgattttaccgacgagacgtccgaagtatctactaccgacaaaattgcggatatcactatcatcatcccgtacatcggtccggctctgaacattggcaacatgctgtacaaagacgacttcgttggcgcactgatcttctccggtgcggtgatcctgctggagttcatcccggaaatcgccatcccggtactgggcacctttgctctggtttcttacattgcaaacaaggttctgactgtacaaaccatcgacaacgcgctgagcaaacgtaacgaaaaatgggatgaagtttacaaatatatcgtgaccaact9gctggctaaggttaatactcagatcgacctcatccgcaaaaaaatgaaagaagcactggaaaaccaggcggaagctaccaaggcaatcattaactaccagtacaaccagtacaccgaggaagaaaaaaacaacatcaacttcaacatcgacgatctgtcctctaaactgaacgaatccatcaacaaagctatgatcaacatcaacaagttcctgaaccagtgctctgtaagctatctgatgaactccatgatcccgtacggtgttaaacgtctggaggacttcgatgcgtctctgaaagacgccctgctgaaatacatttacgacaaccgtggcactctgatcggtcaggttgatcgtctgaaggacaaagtgaacaataccttatcgaccgacatcccttttcagctcagtaaatatgtcgataaccaacgccttttgtccactctagaataatgaaagctt
SEQ ID2 LHNB
ggatccatgccggttaccatcaacaacttcaactacaacgacccgatcgacaacaacaacatcattatgatggaaccgccgttcgcacgtggtaccggacgttactacaaggcttttaagatcaccgaccgtatctggatcatcccggaacgttacaccttcggttacaaacctgaggacttcaacaagagtagcgggattttcaatcgtgacgtctgcgagtactatgatccagattatctgaataccaacgataagaagaacatattccttcagactatgattaaactcttcaaccgtatcaaaagcaaaccgctcggtgaaaaactcctcgaaatgattatcaacggtatcccgtacctcggtgaccgtcgtgtcccgcttgaagagttcaacaccaacatcgcaagcgtcaccgtcaacaaactcatcagcaacccaggtgaagtcgaacgtaaaaaaggtatcttcgcaaacctcatcatcttcggtccgggtccggtcctcaacgaaaacgaaaccatcgacatcggtatccagaaccacttcgcaagccgtgaaggtttcggtggtatcatgcagatgaaattctgcccggaatacgtcagtgtcttcaacaacgtccaggaaaacaaaggtgcaagcatcttcaaccgtcgtggttacttcagcgacccggcactcatcctcatgcatgaactcatccacgtcctccacggtctctacggtatcaaagttgacgacctcccgatcgtcccgaacgagaagaaattcttcatgcagagcaccgacgcaatccaggctgaggaactctacaccttcggtggccaagacccaagtatcataaccccgtccaccgacaaaagcatctacgacaaagtcctccagaacttcaggggtatcgtggacagactcaacaaagtcctcgtctgcatcagcgacccgaacatcaatatcaacatatacaagaacaagttcaaagacaagtacaaattcgtcgaggacagcgaaggcaaatacagcatcgacgtagaaagtttcgacaagctctacaaaagcctcatgttcggtttcaccgaaaccaacatcgccgagaactacaagatcaagacaagggcaagttacttcagcgacagcctcccgcctgtcaaaatcaagaacctcttagacaacgagatttacacaattgaagagggcttcaacatcagtgacaaagacatggagaaggaatacagaggtcagaacaaggctatcaacaaacaggcatacgaggagatcagcaaagaacacctcgcagtctacaagatccagatgtgcgtcgacgaagaaaagctgtacgacgacgacgacaaagaccgttggggttcttcgctgcagtgcatcgacgttgacaacgaagacctgttcttcatcgctgacaaaaacagcttcagtgacgacctgagcaaaaacgaacgtatcgaatacaacacccagagcaactacatcgaaaacgacttcccgatcaacgaactgatcctggacaccgacctgataagtaaaatcgaactgccgagcgaaaacaccgaaagtctgaccgacttcaacgttgacgttccggtttacgaaaaacagccggctatcaagaaaatcttcaccgacgaaaacaccatcttccagtacctgtacagccagaccttcccgctggacatccgtgacatcagtctgaccagcagtttcgacgacgctctgctgttcagcaacaaagtttacagtttcttcagcatggactacatcaaaaccgctaacaaagttgttgaagcagggctgttcgctggttgggttaaacagatcgttaacgacttcgttatcgaagctaacaaaagcaacactatggacgcaatcgctgacatcagtctgatcgttccgtacatcggtctggctctgaacgttggtaacgaaaccgctaaaggtaactttgaaaacgctttcgagatcgctggtgcaagcatcctgctggagttcatcccggaactgctgatcccggttgttggtgctttcctgctggaaagttacatcgacaacaaaaacaagatcatcaaaaccatcgacaacgctctgaccaaacgtaacgaaaaatggagtgatatgtacggtctgatcgttgctcagtggctgagcaccgtcaacacccagttctacaccatcaaagaaggtatgtacaaagctctgaactaccaggctcaggctctggaagagatcatcaaataccgttacaacatctacagtgagaaggaaaagagtaacatcaacatcgacttcaacgacatcaacagcaaactgaacgaaggtatcaaccaggctatcgacaacatcaacaacttcatcaacggttgcagtgttagctacctgatgaagaagatgatcccgctggctgttgaaaaactgctggacttcgacaacaccctgaaaaagaacctgctgaactacatcgacgaaaacaagctgtacctgatcggtagtgctgaatacgaaaaaagtaaagtgaacaaatacctgaagaccatcatgccgttcgacctgagtatctacaccaacgacaccatcctgatcgaaatgttcaacaaatacaactctctagaataatgaaagctt
SEQ ID3 LHNC
ggatccatgccgatcaccatcaacaacttcaactacagcgatccggtggataacaaaaacatcctgtacctggatacccatctgaataccctggcgaacgaaccggaaaaagcgtttcgtatcaccggcaacatttgggttattccggatcgttttagccgtaacagcaacccgaatctgaataaaccgccgcgtgttaccagcccgaaaagcggttattacgatccgaactatctgagcaccgatagcgataaagataccttcctgaaagaaatcatcaaactgttcaaacgcatcaacagccgtgaaattggcgaagaactgatctatcgcctgagcaccgatattccgtttccgggcaacaacaacaccccgatcaacacctttgatttcgatgtggatttcaacagcgttgatgttaaaacccgccagggtaacaattgggtgaaaaccggcagcattaacccaagcgtgattattaccggtccgcgcgaaaacattattgatccggaaaccagcacctttaaactgaccaacaacacctttgcggcgcaggaaggttttggcgcgctgagcattattagcattagcccgcgctttatgctgacctatagcaacgcgaccaacgatgttggtgaaggccgtttcagcaaaagcgaattttgcatggacccgatcctgatcctgatgcatgaactgaaccatgcgatgcataacctgtatggcatcgcgattccgaacgatcagaccattagcagcgtgaccagcaacatcttttacagccagtacaacgtgaaactggaatatgcggaaatctatgcgtttggcggtccgaccattgatctgattccgaaaagcgcgcgcaaatacttcgaagaaaaagcgctggattactatcgcagcattgcgaaacgtctgaacagcattaccaccgcgaatccgagcagcttcaacaaatatatcggcgaatataaacagaaactgatccgcaaatatcgctttgtggtggaaagcagcggcgaagttaccgttaaccgcaataaattcgtggaactgtacaacgaactgacccagatcttcaccgaatttaactatgcgaaaatctataacgtgcagaaccgtaaaatctacctgagcaacgtgtataccccggtgaccgcgaatattctggatgataacgtgtacgatatccagaacggctttaacatcccgaaaagcaacctgaacgttctgtttatgggccagaacctgagccgtaatccggcgctgcgtaaagtgaacccggaaaacatgctgtacctgttcaccaaattttgcgtcgacgcgattgatggtcgtagcctgtacaacaaaaccctgcagtgtcgtgaactgctggtgaaaaacaccgatctgccgtttattggcgatatcagcgatgtgaaaaccgatatcttcctgcgcaaagatatcaacgaagaaaccgaagtgatctactacccggataacgtgagcgttgatcaggtgatcctgagcaaaaacaccagcgaacatggtcagctggatctgctgtatccgagcattgatagcgaaagcgaaattctgccgggcgaaaaccaggtgttttacgataaccgtacccagaacgtggattacctgaacagctattactacctggaaagccagaaactgagcgataacgtggaagattttacctttacccgcagcattgaagaagcgctggataacagcgcgaaagtttacacctattttccgaccctggcgaacaaagttaatgcgggtgttcagggcggtctgtttctgatgtgggcgaacgatgtggtggaagatttcaccaccaacatcctgcgtaaagataccctggataaaatcagcgatgttagcgcgattattccgtatattggtccggcgctgaacattagcaatagcgtgcgtcgtggcaattttaccgaagcgtttgcggttaccggtgtgaccattctgctggaagcgtttccggaatttaccattccggcgctgggtgcgtttgtgatctatagcaaagtgcaggaacgcaacgaaatcatcaaaaccatcgataactgcctggaacagcgtattaaacgctggaaagatagctatgaatggatgatgggcacctggctgagccgtattatcacccagttcaacaacatcagctaccagatgtacgatagcctgaactatcaggcgggtgcgattaaagcgaaaatcgatctggaatacaaaaaatacagcggcagcgataaagaaaacatcaaaagccaggttgaaaacctgaaaaacagcctggatgtgaaaattagcgaagcgatgaataacatcaacaaattcatccgcgaatgcagcgtgacctacctgttcaaaaacatgctgccgaaagtgatcgatgaactgaacgaatttgatcgcaacaccaaagcgaaactgatcaacctgatcgatagccacaacattattctggtgggcgaagtggataaactgaaagcgaaagttaacaacagcttccagaacaccatcccgtttaacatcttcagctataccaacaacagcctgctgaaagatatcatcaacgaatacttcaatctagactaataagctt
SEQ ID4 LHND
ggatccatgacgtggccagttaaggatttcaactactcagatcctgtaaatgacaacgatattctgtaccttcgcattccacaaaataaactgatcaccacaccagtcaaagcattcatgattactcaaaacatttgggtcattccagaacgcttttctagtgacacaaatccgagtttatctaaacctccgcgtccgacgtccaaatatcagagctattacgatccctcatatctcagtacggacgaacaaaaagatactttccttaaaggtatcattaaactgtttaagcgtattaatgagcgcgatatcgggaaaaagttgattaattatcttgttgtgggttccccgttcatgggcgatagctctacccccgaagacacttttgattttacccgtcatacgacaaacatcgcggtagagaagtttgagaacggatcgtggaaagtcacaaacatcattacacctagcgtcttaatttttggtccgctgccaaacatcttagattatacagccagcctgactttgcaggggcaacagtcgaatccgagtttcgaaggttttggtaccctgagcattctgaaagttgccccggaatttctgctcactttttcagatgtcaccagcaaccagagctcagcagtattaggaaagtcaattttttgcatggacccggttattgcactgatgcacgaactgacgcactctctgcatcaactgtatgggatcaacatccccagtgacaaacgtattcgtccccaggtgtctgaaggatttttctcacaggatgggccgaacgtccagttcgaagagttgtatactttcggaggcctggacgtagagatcattccccagattgagcgcagtcagctgcgtgagaaggcattgggccattataaggatattgcaaaacgcctgaataacattaacaaaacgattccatcttcgtggatctcgaatattgataaatataagaaaatttttagcgagaaatataattttgataaagataatacaggtaactttgtggttaacattgacaaattcaactccctttacagtgatttgacgaatgtaatgagcgaagttgtgtatagttcccaatacaacgttaagaatcgtacccattacttctctcgtcactacctgccggttttcgcgaacatccttgacgataatatttacactattcgtgacggctttaacttgaccaacaagggcttcaatattgaaaattcaggccagaacattgaacgcaacccggccttgcagaaactgtcgagtgaatccgtggttgacctgtttaccaaagtctgcgtcgacaaaagcgaagagaagctgtacgatgacgatgacaaagatcgttggggatcgtccctgcagtgtattaaagtgaaaaacaatcggctgccttatgtagcagataaagatagcattagtcaggagattttcgaaaataaaattatcactgacgaaaccaatgttcagaattattcagataaattttcactggacgaaagcatcttagatggccaagttccgattaacccggaaattgttgatccgttactgccgaacgtgaatatggaaccgttaaacctccctggcgaagagatcgtattttatgatgacattacgaaatatgtggactaccttaattcttattactatttggaaagccagaaactgtccaataacgtggaaaacattactctgaccacaagcgtggaagaggctttaggctactcaaataagatttataccttcctcccgtcgctggcggaaaaagtaaataaaggtgtgcaggctggtctgttcctcaactgggcgaatgaagttgtcgaagactttaccacgaatattatgaaaaaggataccctggataaaatctccgacgtctcggttatttatcccatatattggccctgcgttaaatatcggtaatagtgcgctgcgggggaattttaaccaggcctttgctaccgcgggcgtcgcgttcctcctggagggctttcctgaatttactatcccggcgctcggtgtttttacattttactcttccatccaggagcgtgagaaaattatcaaaaccatcgaaaactgcctggagcagcgggtgaaacgctggaaagattcttatcaatggatggtgtcaaactggttatctcgcatcacgacccaattcaaccatattaattaccagatgtatgatagtctgtcgtaccaagctgacgccattaaagccaaaattgatctggaatataaaaagtactctggtagcgataaggagaacatcaaaagccaggtggagaaccttaagaatagtctggatgtgaaaatctctgaagctatgaataacattaacaaattcattcgtgaatgttcggtgacgtacctgttcaagaatatgctgccaaaagttattgatgaactgaataaatttgatctgcgtaccaaaaccgaacttatcaacctcatcgactcccacaacattatccttgtgggcgaagtggatcgtctgaaggccaaagtaaacgagagctttgaaaatacgatgccgtttaatattttttcatataccaataactccttgctgaaagatatcatcaatgaatatttcaatctagaataataagctt
SEQ ID5 IgA-HNtet
ggatccATGGAGTCCAATCAGCCGGAAAAAAATGGAACCGCGACTAAACCCGAGAATTCGGGGAACACTACGTCGGAAAACGGCCAGACGGAACCTGAGAAGAAACTGGAACTACGAAATGTGTCCGATATCGAGCTATACTCTCAAACCAATGGAACCTATAGGCAGCATGTTTCATTGGACGGAATCCCAGAAAATACGGATACATATTTCGTCAAAGTGAAGTCTAGCGCATTCAAGGATGTATATATCCCCGTTGCGAGTATTACAGAAGAGAAGCGGAACGGTCAAAGCGTTTATAAGATTACAGCAAAGGCCGAAAAGTTACAACAGGAGTTAGAAAACAAATACGTTGACAATTTCACTTTTTATCTCGATAAAAAGGCTAAAGAGGAAAACACGAACTTCACGTCATTTAGTAATCTGGTCAAAGCCATAAATCAAAATCCATCTGGTACATACCATCTCGCGGCAAGTCTAAACGCGAATGAAGTAGAACTTGGCCCGGACGAGCGTTCATACATTAAGGATACCTTTACTGGCAGACTCATAGGGGAAAAAGACGGTAAGAACTATGCTATATACAATTTGAAAAAGCCTTTATTTGAGAACCTGTCGGGCGCCACCGTCGAGAAATTGTCCCTTAAAAACGTAGCTATAAGCGGAAAGAATGACATCGGTAGTCTTGCAAACGAGGCTACTAACGGGACAAAGATTAAACAAGTGCACGTAGATGGGtgtgtcgacggcatcattacctccaaaactaaatctgacgatgacgataaaaacaaagcgctgaacctgcagtgcattaaaataaagaatgaggatttgacattcatcgcagaaaaaaatagcttcagcgaagagccgttccaagatgagatagtaagctacaacaccaagaacaagccgcttaattttaattactcgttagataaaatcatagttgactacaaccttcaatcgaagatcacgttaccgaatgacagaacaactcctgtcacaaaaggaattccctatgcacctgagtataagtcaaatgccgcgtcaacaatagagattcataatatagatgacaacaccatctatcaatatctgtacgctcagaaaagtccaacaactcttcagcgtataacaatgaccaatagtgtcgatgacgcattgataaattctaccaagatatactcttatttcccgagcgtcatctccaaagttaatcaaggtgctcaaggcattctatttttgcaatgggtccgagacatcatagatgacttcactaatgagtcgtctcagaaaaccacgattgataaaatatcagat9tttccaccatcgtcccctacatcggacctgcgcttaacattgtgaagcaggggtatgaggggaattttatcggagcgttagaaactacgggggttgtgctattacttgaatacataccagagataacattgcccgttatagcggccctcagtatcgcagaatcaagtacacaaaaa9aaaagataatcaaaacaatcgacaacttcctagaaaagaggtacgaaaaatggatagaggtttataaactcgtgaaagcgaaatggttaggcactgttaatacgcagttccaaaagagatcctatcaaatgtatagatcactggagtaccaggtggatgccataaagaaaattatcgactatgaatataaaatatattcaggtccagataaggagcagatagctgatgaaataaacaatttaaaaaacaaacttgaagagaaggcgaataaggccatgatcaatatcaatatttttatgcgagaatcttcacgatcttttttggtaaatcagatgattaacgaagccaaaaagcagctgcttgagttcgacacacagtccaaaaacatactaatgcaatatatcaaagcaaactcaaaattcattggaattactgagctgaagaaactggaatccaaaataaataaagtattctctaccccgatcccgttctcttactctaaaaaccttgactgctgggtagataacgaagaagatattgacgttctagagtaataagctt
SEQ ID6 GHRP接头
Catatgccggttggatccatccaggtcgactttaaactgcagggtgttactctagagggcggtggcggtagcggtggcggtggcagcggcggtggcggtagcgcactagtgggcagctcatttctgtctccggaacatcaacgggtgcagcagcgtaaagagagtaaaaagccgccagcgaaattacagcctcgctaatagaagcttaagggcgaattc
SEQ ID7 GHRP-C融合体
catatgccggttggatccatgccgatcaccatcaacaacttcaactacagcgatccggtggataacaaaaacatcctgtacctggatacccatctgaataccctggcgaacgaaccggaaaaagcgtttcgtatcaccggcaacatttgggttattccggatcgttttagccgtaacagcaacccgaatctgaataaaccgccgcgtgttaccagcccgaaaagcggttattacgatccgaactatctgagcaccgatagcgataaagataccttcctgaaagaaatcatcaaactgttcaaacgcatcaacagccgtgaaattggcgaagaactgatctatcgcctgagcaccgatattccgtttccgggcaacaacaacaccccgatcaacacctttgatttcgatgtggatttcaacagcgttgatgttaaaacccgccagggtaacaattgggtgaaaaccggcagcattaacccgagcgtgattattaccggtccgcgcgaaaacattattgatccggaaaccagcacctttaaactgaccaacaacacctttgcggcgcaggaaggttttggcgcgctgagcattattagcattagcccgcgctttatgctgacctatagcaacgcgaccaacgatgttggtgaaggccgtttcagcaaaagcgaattttgcatggacccgatcctgatcctgatgcatgaactgaaccatgcgatgcataacctgtatggcatcgcgattccgaaccgatcagaccattagcagcgtgaccagcaacatcttttacagccagtacaacgtgaaactggaatatgcggaaatctatgcgtttggcggtccgaccattgatctgattccgaaaagcgcgcgcaaatacttcgaagaaaaagcgctggattactatccgcagcattgcgaaacgtctgaacagcattaccaccgcgaatccgagcagcttcaacaaatatatcggcgaatataaacagaaactgatccgcaaatatcgctttgtggtggaaagcagcggcgaagttaccgttaaccgcaataaattcgtggaactgtacaacgaactgacccagatcttcaccgaatttaactatgcgaaaatctataacgtgcagaaccgtaaaatctacctgagcaacgtgtataccccggtgaccgcgaatattctggatgataacgtgtacgatatccagaacggctttaacatcccgaaaagcaacctgaacgttctgtttatgggccagaacctgagccgtaatccggcgctgcgtaaagtgaacccggaaaacatgctgtacctgttcaccaaattttgcgtcgacgcgattgatggtcgtagcctgtacaacaaaaccctgcagtgtcgtgaactgctggtgaaaaacaccgatctgccgtttattggcgatatcagcgatgtgaaaaccgatatcttcctgcgcaaagatatcaacgaagaaaccgaagtgatctactacccggataacgtgagcgttgatcaggtgatcctgagcaaaaacaccagcgaacatggtcagctggatctgctgtatccgagcattgatagcgaaagc9aaattctgccgggcgaaaaccaggtgttttacgataaccgtacccagaacgtggattacctgaacagctattactacctggaaagccagaaactgagcgataacgtggaagattttacctttacccgcagcattgaagaagcgctggataacagcgcgaaagtttacacctattttccgaccctggcgaacaaagttaatgcgggtgttcagggcggtctgtttctgatgtgggcgaacgatgtggtggaagatttcaccaccaacatcctgcgtaaagataccctggataaaatcagcgatgttagcgcgattattccgtatattggtccggcgctgaacattagcaatagcgtgcgtcgtggcaattttaccgaagcgtttgcggttaccggtgtgaccattctgctggaagcgtttccggaatttaccattccggcgctgggtgcgtttgtgatctatagcaaagtgcaggaacgcaacgaaatcatcaaaaccatcgataactgcctggaacagcgtattaaacgctggaaagatagctatgaatggatgatgggcacctggctgagccgtattatcacccagttcaacaacatcagctaccagatgtacgatagcctgaactatcaggcgggtgcgattaaagcgaaaatcgatctggaatacaaaaaatacagcggcagcgataaagaaaacatcaaaagccaggttgaaaacctgaaaaacagcctggatgtgaaaattagcgaagcgatgaataacatcaacaaattcatccgcgaatgcagcgtgacctacctgttcaaaaacatgctgccgaaagtgatcgatgaactgaacgaatttgatcgcaacaccaaagcgaaactgatcaacctgatcgatagccacaacattattctggtgggcgaagtggataaactgaaagcgaaagttaacaacagcttccagaacaccatcccgtttaacatcttcagctataccaacaacagcctgctgaaagatatcatcaacgaatacttcaatctagagggcggtggcggtagcggtggcggtggcagcggcggtggcggtagcgcactagtgggcagctcatttctgtctccggaacatcaacgggtgcagcagcgtaaagagagtaaaaagccgccagcgaaattacagcctcgctaatagaagcttaagggcgaattc
SEQ ID8 GHRP-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVGSSFLSPEHQRVQQRKESKKPPAKLQPR
SEQ ID9 GHRH-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVYADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGA
SEQ ID10 EGF-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVNSDSECPLSHDGYCLHDGVCMYIEALDKYACNCVVGYIGERCQYRDLKWWELR
SEQ ID11 NGF-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSALVEPHSESNVPAGHTIPQAHWTKLQHSLDTALRRARSAPAAAIAARVAGQTRNITVDPRLFKKRRLRSPRVLFSTQPPREAADTQDLDFEVGGAAPFNRTHRSKRSSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDPNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA
SEQ ID12 LEP116-122-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPIRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKIRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVSCHLPWA
SEQ ID13 VIP-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVHSDAVFTDNYTRLRKQMAVKKYLNSILN
SEQ ID14 LEP116-122-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISFAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVSCHLPWA
SEQ ID15 IGF1-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVGPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA
SEQ ID16 SST-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSGGGGSALVAGCKNFFWKTFTSC
SEQ ID17 GHRP-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVGSSFLSPEHQRVQQRKESKKPPAKLQPR
SEQ ID18 IGF1-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVGPETLCGAELVDALQFVCGDRGFYFNKPTGYGSSSRRAPQTGIVDECCFRSCDLRRLEMYCAPLKPAKSA
SEQ ID19 NGF-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVEPHSESNVPAGHTIPQAHWTKLQHSLDTALRRARSAPAAAIAARVAGQTRNITVDPRLFKKRRLRSPRVLFSTQPPREAADTQDLDFEVGGAAPFNRTHRSKRSSSHPIFHRGEFSVCDSVSVWVGDKTTATDIKGKEVMVLGEVNINNSVFKQYFFETKCRDPNPVDSGCRGIDSKHWNSYCTTTHTFVKALTMDGKQAAWRFIRIDTACVCVLSRKAVRRA
SEQ ID20 SST14-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSGGGGSALVAGCKNFFWKTFTSC
SEQ ID21 VIP-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVHSDAVFTDNYTRLRKQMAVKKYLNSILN
SEQ ID22生长素释放肽-A融合体
EFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVDGIITSKTKSDDDDKNKALNLQCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTLEGGGGSGGGGSGGGGSALVGSSFLSPEHQRVQQRKESKKPPAKLQPR
SEQ ID23 CP-hGHRH29 N8A K12N M27L-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSIEGRYADAIFTASYRNVLGQLSARKLLQDILSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID24 N-末端-hGHRH29 N8A M27L-LHD融合体的蛋白序列
HVDAIFTQSYRKVLAQLSARKLLQDILNRNNNNNNNNNNTWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPAL
QKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID25 IgA-HNtet-SST14融合体
ESNQPEKNGTATKPENSGNTTSENGQTEPEKKLELRNVSDIELYSQTNGTYRQHVSLDGIPENTDTYFVKVKSSAFKDVYIPVASITEEKRNGQSVYKITAKAEKLQQELENKYVDNFTFYLDKKAKEENTNFTSFSNLVKAINQNPSGTYHLAASLNANEVELGPDERSYIKDTFTGRLIGEKDGKNYAIYNLKKPLFENLSGATVEKLSLKNVAISGKNDIGSLANEATNGTKIKQVHVDGCVDGIITSKTKSDDDDKNKALNLQCIKIKNEDLTFIAEKNSFSEEPFQDEIVSYNTKNKPLNFNYSLDKIIVDYNLQSKITLPNDRTTPVTKGIPYAPEYKSNAASTIEIHNIDDNTIYQYLYAQKSPTTLQRITMTNSVDDALINSTKIYSYFPSVISKVNQGAQGILFLQWVRDIIDDFTNESSQKTTIDKISDVSTIVPYIGPALNIVKQGYEGNFIGALETTGVVLLLEYIPEITLPVIAALSIAESSTQKEKIIKTIDNFLEKRYEKWIEVYKLVKAKWLGTVNTQFQKRSYQMYRSLEYQVDAIKKIIDYEYKIYSGPDKEQIADEINNLKNKLEEKANKAMININIFMRESSRSFLVNQMINEAKKQLLEFDTQSKNILMQYIKANSKFIGITELKKLESKINKVFSTPIPFSYSKNLDCWVDNEEDIDVLEGGGGSGGGGSGGGGSALVAGCKNFFWKTFTSC
SEQ ID26 IgA-HNtet-GHRP融合体
ESNQPEKNGTATKPENSGNTTSENGQTEPEKKLELRNVSDIELYSQTNGTYRQHVSLDGIPENTDTYFVKVKSSAFKDVYIPVASITEEKRNGQSVYKITAKAEKLQQELENKYVDNFTFYLDKKAKEENTNFTSFSNLVKAINQNPSGTYHLAASLNANEVELGPDERSYIKDTFTGRLIGEKDGKNYAIYNLKKPLFENLSGATVEKLSLKNVAISGKNDIGSLANEATNGTKIKQVHVDGCVDGIITSKTKSDDDDKNKALNLQCIKIKNEDLTFIAEKNSFSEEPFQDEIVSYNTKNKPLNFNYSLDKIIVDYNLQSKITLPNDRTTPVTKGIPYAPEYKSNAASTIEIHNIDDNTIYQYLYAQKSPTTLQRITMTNSVDDALINSTKIYSYFPSVISKVNQGAQGILFLQWVRDIIDDFTNESSQKTTIDKISDVSTIVPYIGPALNIVKQGYEGNFIGALETTGVVLLLEYIPEITLPVIAALSIAESSTQKEKIIKTIDNFLEKRYEKWIEVYKLVKAKWLGTVNTQFQKRSYQMYRSLEYQVDAIKKIIDYEYKIYSGPDKEQIADEINNLKNKLEEKANKAMININIFMRESSRSFLVNQMINEAKKQLLEFDTQSKNILMQYIKANSKFIGITELKKLESKINKVFSTPIPFSYSKNLDCWVDNEEDIDVLEGGGGSGGGGSGGGGSALVGSSFLSPEHQRVQQRKESKKPPAKLQPR
SEQ ID27生长素释放肽S3W-A融合体
EFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVDGIITSKTKSDDDDKNKALNLQCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTLEIYALVGSWFLSPEHQRVQQRKESKKPPAKLQPR
SEQ ID28 SST28-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSGGGGSGGGGSALVSANSNPAMAPRERKAGCKNFFWKTFTSC
SEQ ID29 GRP-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVGNHWAVGHLM
SEQ ID30 GRP-B融合体
PVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFNKSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLYGIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIVDRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCVDEEKLYDDDDKDRWGSSLQCIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSNYIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQYLYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDAIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMYKALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSVSYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNSLEGGGGSGGGGSGGGGSALVGNHWAVGHLM
SEQ ID31 CP-qGHRH29接头
ggatccGTCGACaacaacaataacaacaacaataacaacaacgacgatgacgataaaCATGTGGATGCGATCTTTACCCAGAGCTATCGGAAGGTTTTGGCCCAACTGTCTGCTCGTAAACTTTTACAGGACATTCTGAACAGAGCAgaagcggcagccaaagaagcagccgctaaggcgctgcagagtctagaataataagctt
SEQ ID32 CP-qGHRH29-D融合体
ggatccatgacgtggccagttaaggatttcaactactcagatcctgtaaatgacaacgatattctgtaccttcgcattccacaaaataaactgatcaccacaccagtcaaagcattcatgattactcaaaacatttgggtcattccagaacgcttttctagtgacacaaatccgagtttatctaaacctccgcgtccgacgtccaaatatcagagctattacgatccctcatatctcagtacggacgaacaaaaagatactttccttaaaggtatcattaaactgtttaagcgtattaatgagcgcgatatcgggaaaaagttgattaattatcttgttgtgggttccccgttcatgggcgatagctctacccccgaagacacttttgattttacccgtcatacgacaaacatcgcggtagagaagtttgagaacggatcgtggaaagtcacaaacatcattacacctagcgtcttaatttttggtccgctgccaaacatcttagattatacagccagcctgactttgcaggggcaacagtcgaatccgagtttcgaaggttttggtaccctgagcattctgaaagttgccccggaatttctgctcactttttcagatgtcaccagcaaccagagctcagcagtattaggaaagtcaattttttgcatggacccggttattgcactgatgcacgaactgacgcactctctgcatcaactgtatgggatcaacatccccagtgacaaacgtattcgtccccaggtgtctgaaggatttttctcacaggatgggccgaacgtccagttcgaagagttgtatactttcggaggcctggacgtagagatcattccccagattgagcgcagtcagctgcgtgagaaggcattgggccattataaggatattgcaaaacgcctgaataacattaacaaaacgattccatcttcgtggatctcgaatattgataaatataagaaaatttttagcgagaaatataattttgataaagataatacaggtaactttgtggttaacattgacaaattcaactccctttacagtgatttgacgaatgtaatgagcgaagttgtgtatagttcccaatacaacgttaagaatcgtacccattacttctctcgtcactacctgccggttttcgcgaacatccttgacgataatatttacactattcgtgacggctttaacttgaccaacaagggcttcaatattgaaaattcaggccagaacattgaacgcaacccggccttgcagaaactgtcgagtgaatccgtggttgacctgtttaccaaagtctgcGTCGACaacaacaataacaacaacaataacaacaacgacgatgacgataaaCATGTGGATGCGATCTTTACCCAGAGCTATCGGAAGGTTTTGGCCCAACTGTCTGCTCGTAAACTTTTACAGGACATTCTGAACAGAGCAgaagcggcagccaaagaagcagccgctaaggcgctgcagtgtattaaagtgaaaaacaatcggctgccttatgtagcagataaagatagcattagtcaggagattttcgaaaataaaattatcactgacgaaaccaatgttcagaattattcagataaattttcactggacgaaagcatcttagatggccaagttccgattaacccggaaattgttgatccgttactgccgaacgtgaatatggaaccgttaaacctccctggcgaagagatcgtattttatgatgacattacgaaatatgtggactaccttaattcttattactatttggaaagccagaaactgtccaataacgtggaaaacattactctgaccacaagcgtggaagaggctttaggctactcaaataagatttataccttcctcccgtcgctggcggaaaaagtaaataaaggtgtgcaggctggtctgttcctcaactgggcgaatgaagttgtcgaagactttaccacgaatattatgaaaaaggataccctggataaaatctccgacgtctcggttattatcccatatattggccctgcgttaaatatcggtaatagtgcgctgcgggggaattttaaccaggcctttgctaccgcgggcgtcgcgttcctcctggagggctttcctgaatttactatcccggcgctcggtgtttttacattttactcttccatccaggagcgtgagaaaattatcaaaaccatcgaaaactgcctggagcagcgggtgaaacgctggaaagattcttatcaatggatggtgtcaaactggttatctcgcatcacgacccaattcaaccatattaattaccagatgtatgatagtctgtcgtaccaagctgacgccattaaagccaaaattgatctggaatataaaaagtactctggtagcgataaggagaacatcaaaagccaggtggagaaccttaagaatagtctggatgtgaaaatctctgaagctatgaataacattaacaaattcattcgtgaatgttcggtgacgtacctgttcaagaatatgctgccaaaagttattgatgaactgaataaatttgatctgcgtaccaaaaccgaacttatcaacctcatcgactcccacaacattatccttgtgggcgaagtggatcgtctgaaggccaaagtaaacgaga9ctttgaaaatacgatgccgtttaatattttttcatataccaataactccttgctgaaagatatcatcaatgaatatttcaatctagaataatgaaagctt
SEQ ID33 CP-qGHRH29-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDNNNNNNNNNNDDDDKHVDAIFTQSYRKVLAQLSARKLLQDILNRAEAAAKEAAAKALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID34 CP-qGHRH-A融合体
EFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVDGIITSKTKSLIEGRHVDAIFTQSYRKVLAQLSARKLLQDILNRQQGERNQEQGALAGGGGSGGGGSGGGGSALVLQCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLST
SEQ ID35 CP-qGHRH-C融合体
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRHVDAIFTQSYRKVLAQLSARKLLQDILNRQQGERNQEQGALAGGGGSGGGGSGGGGSALVLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFN
SEQ ID36 CP-qGHRH-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKHVDAIFTQSYRKVLAQLSARKLLQDILNRQQGERNQEQGAALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID37 CP-qGHRH-D N10-PL5融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDNNNNNNNNNNDDDDKHVDAIFTQSYRKVLAQLSARKLLQDILNRQQGERNQEQGAPAPAPLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID38 CP-qGHRH-D N10-HX12融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDNNNNNNNNNNDDDDKHVDAIFTQSYRKVLAQLSARKLLQDILNRQQGERNQEQGAEAAAKEAAAKALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID39 CP-SST28-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKSANSNPAMAPRERKAGCKNFFWKTFTSCALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID40 CP-SST14-D融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKAGCKNFFWKTFTSCALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID41 IgA-CP-SSTI 4-HNtet融合体
ESNQPEKNGTATKPENSGNTTSENGQTEPEKKLELRNVSDIELYSQTNGTYRQHVSLDGIPENTDTYFVKVKSSAFKDVYIPVASITEEKRNGQSVYKITAKAEKLQQELENKYVDNFTFYLDKKAKEENTNFTSFSNLVKAINQNPSGTYHLAASLNANEVELGPDERSYIKDTFTGRLIGEKDGKNYAIYNLKKPLFENLSGATVEKLSLKNVAISGKNDIGSLANEATNGTKIKQVHVDGCVDGIITSKTKSDDDDKAGCKNFFWKTFTSCALAGGGGSGGGGSGGGGSALALQCIKIKNEDLTFIAEKNSFSEEPFQDEIVSYNTKNKPLNFNYSLDKIIVDYNLQSKITLPNDRTTPVTKGIPYAPEYKSNAASTIEIHNIDDNTIYQYLYAQKSPTTLQRITMTNSVDDALINSTKIYSYFPSVISKVNQGAQGILFLQWVRDIIDDFTNESSQKTTIDKISDVSTIVPYIGPALNIVKQGYEGNFIGALETTGVVLLLEYIPEITLPVIAALSIAESSTQKEKIIKTIDNFLEKRYEKWIEVYKLVKAKWLGTVNTQFQKRSYQMYRSLEYQVDAIKKIIDYEYKIYSGPDKEQIADEINNLKNKLEEKANKAMININIFMRESSRSFLVNQMINEAKKQLLEFDTQSKNILMQYIKANSKFIGITELKKLESKINKVFSTPIPFSYSKNLDCWVDNEEDIDV
SEQ ID42 CP-UTS-A融合体
EFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVDGGGGSADDDDKNDDPPISIDLTFHLLRNMIEMARIENEREQAGLNRKYLDEVALAGGGGSGGGGSGGGGSALVLQCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLST
SEQ ID43 CP-hTGF-B GS10-NS融合体
PVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFNKSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLYGIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIVDRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCVDGGGGSGGGGSADDDDKVVSHFNDCPDSHTQFCFHGTCRFLVQEDKPACVCHSGYVGARCEHADLLAALAKRLVLQCIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSNYIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQYLYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDAIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMYKALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSVSYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNS
SEQ ID44 CP-hTGF-B GS10-GS20融合体
PVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFNKSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLYGIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIVDRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCVDGGGGSGGGGSADDDDKVVSHFNDCPDSHTQFCFHGTCRFLVQEDKPACVCHSGYVGARCEHADLLAALAGGGGSGGGGSGGGGSALVLQCIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSNYIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQYLYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDAIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMYKALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSVSYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNS
SEQ ID45 LHN/A的蛋白序列
EFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVDGIITSKTKSDDDDKNKALNLQCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLST
SEQ ID46 LHN/B的蛋白序列
PVTINNFNYNDPIDNNNIIMMEPPFARGTGRYYKAFKITDRIWIIPERYTFGYKPEDFNKSSGIFNRDVCEYYDPDYLNTNDKKNIFLQTMIKLFNRIKSKPLGEKLLEMIINGIPYLGDRRVPLEEFNTNIASVTVNKLISNPGEVERKKGIFANLIIFGPGPVLNENETIDIGIQNHFASREGFGGIMQMKFCPEYVSVFNNVQENKGASIFNRRGYFSDPALILMHELIHVLHGLYGIKVDDLPIVPNEKKFFMQSTDAIQAEELYTFGGQDPSIITPSTDKSIYDKVLQNFRGIVDRLNKVLVCISDPNININIYKNKFKDKYKFVEDSEGKYSIDVESFDKLYKSLMFGFTETNIAENYKIKTRASYFSDSLPPVKIKNLLDNEIYTIEEGFNISDKDMEKEYRGQNKAINKQAYEEISKEHLAVYKIQMCVDEEKLYDDDDKDRWGSSLQCIDVDNEDLFFIADKNSFSDDLSKNERIEYNTQSNYIENDFPINELILDTDLISKIELPSENTESLTDFNVDVPVYEKQPAIKKIFTDENTIFQYLYSQTFPLDIRDISLTSSFDDALLFSNKVYSFFSMDYIKTANKVVEAGLFAGWVKQIVNDFVIEANKSNTMDAIADISLIVPYIGLALNVGNETAKGNFENAFEIAGASILLEFIPELLIPVVGAFLLESYIDNKNKIIKTIDNALTKRNEKWSDMYGLIVAQWLSTVNTQFYTIKEGMYKALNYQAQALEEIIKYRYNIYSEKEKSNINIDFNDINSKLNEGINQAIDNINNFINGCSVSYLMKKMIPLAVEKLLDFDNTLKKNLLNYIDENKLYLIGSAEYEKSKVNKYLKTIMPFDLSIYTNDTILIEMFNKYNS
SEQ ID47 LHN/C的蛋白序列
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDAIDGRSLYNKTLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFN
SEQ ID48 LHN/D的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID49 IgA-HNtet的蛋白序列
ESNQPEKNGTATKPENSGNTTSENGQTEPEKKLELRNVSDIELYSQTNGTYRQHVSLDGIPENTDTYFVKVKSSAFKDVYIPVASITEEKRNGQSVYKITAKAEKLQQELENKYVDNFTFYLDKKAKEENTNFTSFSNLVKAINQNPSGTYHLAASLNANEVELGPDERSYIKDTFTGRLIGEKDGKNYAIYNLKKPLFENLSGATVEKLSLKNVAISGKNDIGSLANEATNGTKIKQVHVDGCVDGIITSKTKSDDDDKNKALNLQCIKIKNEDLTFIAEKNSFSEEPFQDEIVSYNTKNKPLNFNYSLDKIIVDYNLQSKITLPNDRTTPVTKGIPYAPEYKSNAASTIEIHNIDDNTIYQYLYAQKSPTTLQRITMTNSVDDALINSTKIYSYFPSVISKVNQGAQGILFLQWVRDIIDDFTNESSQKTTIDKISDVSTIVPYIGPALNIVKQGYEGNFIGALETTGVVLLLEYIPEITLPVIAALSIAESSTQKEKIIKTIDNFLEKRYEKWIEVYKLVKAKWLGTVNTQFQKRSYQMYRSLEYQVDAIKKIIDYEYKIYSGPDKEQIADEINNLKNKLEEKANKAMININIFMRESSRSFLVNQMINEAKKQLLEFDTQSKNILMQYIKANSKFIGITELKKLESKINKVFSTPIPFSYSKNLDCWVDNEEDIDV
SEQ ID50合成的奥曲肽
Cys-Dphe-Cys-Phe-Dtrp-Lys-Thr-Cys-Thr-ol
SEQ ID51合成的GHRH激动剂肽
HIS-ALA-ASP-ALA-ILE-PHE-THR-ASN-SER-TYR-ARG-LYS-VAL-LEU-GLY-GLN-LEU-SER-ALA-ARG-LYS-LEU-LEU-GLN-ASP-ILE-NLE-SER-ARG-CYS
SEQ ID52合成的GHRH拮抗剂肽
PhAc-Tyr-D-Arg-Asp-Ala-Ile-Phe(4-Cl)-Thr-Ala-Har-Tyr(Me)-His-Lys-VaI-Leu-Abu-Gln-Leu-Ser-Ala-His-Lys-Leu-Leu-Gln-Asp-IIe-Nle-D-Arg-Har-CYS
SEQ ID53 CP-MCH-D融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKDFDMLRCMLGRVYRPCWQVALAKRLVLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID54 KISS-D融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDKSEEKLYDDDDKDRWGSSLQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFNLEGGGGSGGGGSGGGGSALVYNWNSFGLRFG
SEQ ID55 PrRP-A融合体的蛋白序列
EFVNKQFNYKDPVNGVDIAYIKIPNAGQMQPVKAFKIHNKIWVIPERDTFTNPEEGDLNPPPEAKQVPVSYYDSTYLSTDNEKDNYLKGVTKLFERIYSTDLGRMLLTSIVRGIPFWGGSTIDTELKVIDTNCINVIQPDGSYRSEELNLVIIGPSADIIQFECKSFGHEVLNLTRNGYGSTQYIRFSPDFTFGFEESLEVDTNPLLGAGKFATDPAVTLAHELIHAGHRLYGIAINPNRVFKVNTNAYYEMSGLEVSFEELRTFGGHDAKFIDSLQENEFRLYYYNKFKDIASTLNKAKSIVGTTASLQYMKNVFKEKYLLSEDTSGKFSVDKLKFDKLYKMLTEIYTEDNFVKFFKVLNRKTYLNFDKAVFKINIVPKVNYTIYDGFNLRNTNLAANFNGQNTEINNMNFTKLKNFTGLFEFYKLLCVDGIITSKTKSDDDDKNKALNLQCIKVNNWDLFFSPSEDNFTNDLNKGEEITSDTNIEAAEENISLDLIQQYYLTFNFDNEPENISIENLSSDIIGQLELMPNIERFPNGKKYELDKYTMFHYLRAQEFEHGKSRIALTNSVNEALLNPSRVYTFFSSDYVKKVNKATEAAMFLGWVEQLVYDFTDETSEVSTTDKIADITIIIPYIGPALNIGNMLYKDDFVGALIFSGAVILLEFIPEIAIPVLGTFALVSYIANKVLTVQTIDNALSKRNEKWDEVYKYIVTNWLAKVNTQIDLIRKKMKEALENQAEATKAIINYQYNQYTEEEKNNINFNIDDLSSKLNESINKAMININKFLNQCSVSYLMNSMIPYGVKRLEDFDASLKDALLKYIYDNRGTLIGQVDRLKDKVNNTLSTDIPFQLSKYVDNQRLLSTLEGGGGSGGGGSGGGGSALVTPDINPAWYASRGIRPVGRFG
SEQ ID56 CP-CRH-C融合体的蛋白序列
PITINNFNYSDPVDNKNILYLDTHLNTLANEPEKAFRITGNIWVIPDRFSRNSNPNLNKPPRVTSPKSGYYDPNYLSTDSDKDTFLKEIIKLFKRINSREIGEELIYRLSTDIPFPGNNNTPINTFDFDVDFNSVDVKTRQGNNWVKTGSINPSVIITGPRENIIDPETSTFKLTNNTFAAQEGFGALSIISISPRFMLTYSNATNDVGEGRFSKSEFCMDPILILMHELNHAMHNLYGIAIPNDQTISSVTSNIFYSQYNVKLEYAEIYAFGGPTIDLIPKSARKYFEEKALDYYRSIAKRLNSITTANPSSFNKYIGEYKQKLIRKYRFVVESSGEVTVNRNKFVELYNELTQIFTEFNYAKIYNVQNRKIYLSNVYTPVTANILDDNVYDIQNGFNIPKSNLNVLFMGQNLSRNPALRKVNPENMLYLFTKFCVDGGGGSADDDDKSEEPPISLDLTFHLLREVLEMARAEQLAQQAHSNRKLMEIIALAGGGGSGGGGSGGGGSALVLQCRELLVKNTDLPFIGDISDVKTDIFLRKDINEETEVIYYPDNVSVDQVILSKNTSEHGQLDLLYPSIDSESEILPGENQVFYDNRTQNVDYLNSYYYLESQKLSDNVEDFTFTRSIEEALDNSAKVYTYFPTLANKVNAGVQGGLFLMWANDVVEDFTTNILRKDTLDKISDVSAIIPYIGPALNISNSVRRGNFTEAFAVTGVTILLEAFPEFTIPALGAFVIYSKVQERNEIIKTIDNCLEQRIKRWKDSYEWMMGTWLSRIITQFNNISYQMYDSLNYQAGAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNEFDRNTKAKLINLIDSHNIILVGEVDKLKAKVNNSFQNTIPFNIFSYTNNSLLKDIINEYFN
SEQ ID57 CP-HS_GHRH_1-27-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLGQLSARKLLQDIMALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID58 CP-HS_GHRH_1-28-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLGQLSARKLLQDIMSALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID59 CP-HS_GHRH_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID60 CP-HS_GHRH_1-44-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGARARLALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID61 CP-HS_GHRH_1-40-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLGQLSARKLLQDIMSRQQGESNQERGALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID62 CP-HS_GHRH_Ala9-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNAYRKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID63 CP-HS_GHRH_Ala22-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLGQLSARKALQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEWEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID64 CP-HS_GHRH_Ala8_Lys11_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYKKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID65蛋白CP-HS_GHRH_Ala8_Lys11_Arg12_1-29-LHD融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYKRVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID66 CP-HS_GHRH_Ala8_Asn11_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYNKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID67 CP-HS_GHRH_Ala8_Lys20_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRKVLGQLSAKKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID68蛋白CP-HS_GHRH_Ala8_Lysl1_Lys20_1-29-LHD融合体
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYKKVLGQLSAKKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID69 CP-HS_GHRH_Ala8_Asn20_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRKVLGQLSANKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID70 CP-HS_GHRH_Ala8_Asn12_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRNVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID71 CP-HS_GHRH_Ala8_Asn21_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRKVLGQLSARNLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID72 CP-HS_GHRH_Ala8Glu_7_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFEASYRKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID73 CP-HS_GHRH_Ala8Glu_10_1-29LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASERKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID74 CP-HS_GHRH_Ala8Glu_13_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRKELGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID75 CP-HS_GHRH_Ala8-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID76 CP-HS_GHRH_Glu8_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTESYRKVLGQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID77 CP-HS_GHRH_A1a15_1-27-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLAQLSARKLLQDIMALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID78 CP-HS_GHRH_Ala15-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTNSYRKVLAQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID79 CP-HS_GHRH_Ala8_Ala15_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTASYRKVLAQLSARKLLQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID80 CP-HS_GHRH_Ala8_9_15_22_27-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTAAYRKVLAQLSARKALQDIASRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID81 CP-HS_GHRH_Ala8_9_15_22-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTAAYRKVLAQLSARKALQDIMSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID82 CP-HS_GHRH_HVQAL_1-32-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKHVDAIFTQSYRKVLAQLSARKALQDILSRQQGALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID83 CP-HS_GHRH_HVSAL_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKHVDAIFTSSYRKVLAQLSARKLLQDILSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID84 CP-HS_GHRH_HVTAL_1-29-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKHVDAIFTTSYRKVLAQLSARKLLQDILSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID85 CP-HS_GHRH_QALN-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTQSYRKVLAQLSARKALQDILNRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID86 CP-HS_GHRH_QAL-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIITSKTKSDDDDKYADAIFTQSYRKVLAQLSARKALQDILSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
SEQ ID87 CP-hGHRH29 N8A M27L-LHD融合体的蛋白序列
TWPVKDFNYSDPVNDNDILYLRIPQNKLITTPVKAFMITQNIWVIPERFSSDTNPSLSKPPRPTSKYQSYYDPSYLSTDEQKDTFLKGIIKLFKRINERDIGKKLINYLVVGSPFMGDSSTPEDTFDFTRHTTNIAVEKFENGSWKVTNIITPSVLIFGPLPNILDYTASLTLQGQQSNPSFEGFGTLSILKVAPEFLLTFSDVTSNQSSAVLGKSIFCMDPVIALMHELTHSLHQLYGINIPSDKRIRPQVSEGFFSQDGPNVQFEELYTFGGLDVEIIPQIERSQLREKALGHYKDIAKRLNNINKTIPSSWISNIDKYKKIFSEKYNFDKDNTGNFVVNIDKFNSLYSDLTNVMSEVVYSSQYNVKNRTHYFSRHYLPVFANILDDNIYTIRDGFNLTNKGFNIENSGQNIERNPALQKLSSESVVDLFTKVCVDGIlTSKTKSIEGRYADAIFTASYRKVLGQLSARKLLQDILSRALAGGGGSGGGGSGGGGSALALQCIKVKNNRLPYVADKDSISQEIFENKIITDETNVQNYSDKFSLDESILDGQVPINPEIVDPLLPNVNMEPLNLPGEEIVFYDDITKYVDYLNSYYYLESQKLSNNVENITLTTSVEEALGYSNKIYTFLPSLAEKVNKGVQAGLFLNWANEVVEDFTTNIMKKDTLDKISDVSVIIPYIGPALNIGNSALRGNFNQAFATAGVAFLLEGFPEFTIPALGVFTFYSSIQEREKIIKTIENCLEQRVKRWKDSYQWMVSNWLSRITTQFNHINYQMYDSLSYQADAIKAKIDLEYKKYSGSDKENIKSQVENLKNSLDVKISEAMNNINKFIRECSVTYLFKNMLPKVIDELNKFDLRTKTELINLIDSHNIILVGEVDRLKAKVNESFENTMPFNIFSYTNNSLLKDIINEYFN
序列表
<110> 益普生生物创新有限公司
<120> 癌症的抑制
<130> P31459WO
<140> PCT/GB2009/050666
<141> 2009-06-11
<150> GB 0820965.2
<151> 2008-11-17
<150> GB 0810782.3
<151> 2008-06-12
<160> 87
<170> PatentIn version 3.5
<210> 1
<211> 2619
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 1
ggatccatgg agttcgttaa caaacagttc aactataaag acccagttaa cggtgttgac 60
attgcttaca tcaaaatccc gaacgctggc cagatgcagc cggtaaaggc attcaaaatc 120
cacaacaaaa tctgggttat cccggaacgt gataccttta ctaacccgga agaaggtgac 180
ctgaacccgc caccggaagc gaaacaggtg ccggtatctt actatgactc cacctacctg 240
tctaccgata acgaaaagga caactacctg aaaggtgtta ctaaactgtt cgagcgtatt 300
tactccaccg acctgggccg tatgctgctg actagcatcg ttcgcggtat cccgttctgg 360
ggcggttcta ccatcgatac cgaactgaaa gtaatcgaca ctaactgcat caacgttatt 420
cagccggacg gttcctatcg ttccgaagaa ctgaacctgg tgatcatcgg cccgtctgct 480
gatatcatcc agttcgagtg taagagcttt ggtcacgaag ttctgaacct cacccgtaac 540
ggctacggtt ccactcagta catccgtttc tctccggact tcaccttcgg ttttgaagaa 600
tccctggaag tagacacgaa cccactgctg ggcgctggta aattcgcaac tgatcctgcg 660
gttaccctgg ctcacgaact gattcatgca ggccaccgcc tgtacggtat cgccatcaat 720
ccgaaccgtg tcttcaaagt taacaccaac gcgtattacg agatgtccgg tctggaagtt 780
agcttcgaag aactgcgtac ttttggcggt cacgacgcta aattcatcga ctctctgcaa 840
gaaaacgagt tccgtctgta ctactataac aagttcaaag atatcgcatc caccctgaac 900
aaagcgaaat ccatcgtggg taccactgct tctctccagt acatgaagaa cgtttttaaa 960
gaaaaatacc tgctcagcga agacacctcc ggcaaattct ctgtagacaa gttgaaattc 1020
gataaacttt acaaaatgct gactgaaatt tacaccgaag acaacttcgt taagttcttt 1080
aaagttctga accgcaaaac ctatctgaac ttcgacaagg cagtattcaa aatcaacatc 1140
gtgccgaaag ttaactacac tatctacgat ggtttcaacc tgcgtaacac caacctggct 1200
gctaatttta acggccagaa cacggaaatc aacaacatga acttcacaaa actgaaaaac 1260
ttcactggtc tgttcgagtt ttacaagctg ctgtgcgtcg acggcatcat tacctccaaa 1320
actaaatctg acgatgacga taaaaacaaa gcgctgaacc tgcagtgtat caaggttaac 1380
aactgggatt tattcttcag cccgagtgaa gacaacttca ccaacgacct gaacaaaggt 1440
gaagaaatca cctcagatac taacatcgaa gcagccgaag aaaacatctc gctggacctg 1500
atccagcagt actacctgac ctttaatttc gacaacgagc cggaaaacat ttctatcgaa 1560
aacctgagct ctgatatcat cggccagctg gaactgatgc cgaacatcga acgtttccca 1620
aacggtaaaa agtacgagct ggacaaatat accatgttcc actacctgcg cgcgcaggaa 1680
tttgaacacg gcaaatcccg tatcgcactg actaactccg ttaacgaagc tctgctcaac 1740
ccgtcccgtg tatacacctt cttctctagc gactacgtga aaaaggtcaa caaagcgact 1800
gaagctgcaa tgttcttggg ttgggttgaa cagcttgttt atgattttac cgacgagacg 1860
tccgaagtat ctactaccga caaaattgcg gatatcacta tcatcatccc gtacatcggt 1920
ccggctctga acattggcaa catgctgtac aaagacgact tcgttggcgc actgatcttc 1980
tccggtgcgg tgatcctgct ggagttcatc ccggaaatcg ccatcccggt actgggcacc 2040
tttgctctgg tttcttacat tgcaaacaag gttctgactg tacaaaccat cgacaacgcg 2100
ctgagcaaac gtaacgaaaa atgggatgaa gtttacaaat atatcgtgac caactggctg 2160
gctaaggtta atactcagat cgacctcatc cgcaaaaaaa tgaaagaagc actggaaaac 2220
caggcggaag ctaccaaggc aatcattaac taccagtaca accagtacac cgaggaagaa 2280
aaaaacaaca tcaacttcaa catcgacgat ctgtcctcta aactgaacga atccatcaac 2340
aaagctatga tcaacatcaa caagttcctg aaccagtgct ctgtaagcta tctgatgaac 2400
tccatgatcc cgtacggtgt taaacgtctg gaggacttcg atgcgtctct gaaagacgcc 2460
ctgctgaaat acatttacga caaccgtggc actctgatcg gtcaggttga tcgtctgaag 2520
gacaaagtga acaatacctt atcgaccgac atcccttttc agctcagtaa atatgtcgat 2580
aaccaacgcc ttttgtccac tctagaataa tgaaagctt 2619
<210> 2
<211> 2634
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 2
ggatccatgc cggttaccat caacaacttc aactacaacg acccgatcga caacaacaac 60
atcattatga tggaaccgcc gttcgcacgt ggtaccggac gttactacaa ggcttttaag 120
atcaccgacc gtatctggat catcccggaa cgttacacct tcggttacaa acctgaggac 180
ttcaacaaga gtagcgggat tttcaatcgt gacgtctgcg agtactatga tccagattat 240
ctgaatacca acgataagaa gaacatattc cttcagacta tgattaaact cttcaaccgt 300
atcaaaagca aaccgctcgg tgaaaaactc ctcgaaatga ttatcaacgg tatcccgtac 360
ctcggtgacc gtcgtgtccc gcttgaagag ttcaacacca acatcgcaag cgtcaccgtc 420
aacaaactca tcagcaaccc aggtgaagtc gaacgtaaaa aaggtatctt cgcaaacctc 480
atcatcttcg gtccgggtcc ggtcctcaac gaaaacgaaa ccatcgacat cggtatccag 540
aaccacttcg caagccgtga aggtttcggt ggtatcatgc agatgaaatt ctgcccggaa 600
tacgtcagtg tcttcaacaa cgtccaggaa aacaaaggtg caagcatctt caaccgtcgt 660
ggttacttca gcgacccggc actcatcctc atgcatgaac tcatccacgt cctccacggt 720
ctctacggta tcaaagttga cgacctcccg atcgtcccga acgagaagaa attcttcatg 780
cagagcaccg acgcaatcca ggctgaggaa ctctacacct tcggtggcca agacccaagt 840
atcataaccc cgtccaccga caaaagcatc tacgacaaag tcctccagaa cttcaggggt 900
atcgtggaca gactcaacaa agtcctcgtc tgcatcagcg acccgaacat caatatcaac 960
atatacaaga acaagttcaa agacaagtac aaattcgtcg aggacagcga aggcaaatac 1020
agcatcgacg tagaaagttt cgacaagctc tacaaaagcc tcatgttcgg tttcaccgaa 1080
accaacatcg ccgagaacta caagatcaag acaagggcaa gttacttcag cgacagcctc 1140
ccgcctgtca aaatcaagaa cctcttagac aacgagattt acacaattga agagggcttc 1200
aacatcagtg acaaagacat ggagaaggaa tacagaggtc agaacaaggc tatcaacaaa 1260
caggcatacg aggagatcag caaagaacac ctcgcagtct acaagatcca gatgtgcgtc 1320
gacgaagaaa agctgtacga cgacgacgac aaagaccgtt ggggttcttc gctgcagtgc 1380
atcgacgttg acaacgaaga cctgttcttc atcgctgaca aaaacagctt cagtgacgac 1440
ctgagcaaaa acgaacgtat cgaatacaac acccagagca actacatcga aaacgacttc 1500
ccgatcaacg aactgatcct ggacaccgac ctgataagta aaatcgaact gccgagcgaa 1560
aacaccgaaa gtctgaccga cttcaacgtt gacgttccgg tttacgaaaa acagccggct 1620
atcaagaaaa tcttcaccga cgaaaacacc atcttccagt acctgtacag ccagaccttc 1680
ccgctggaca tccgtgacat cagtctgacc agcagtttcg acgacgctct gctgttcagc 1740
aacaaagttt acagtttctt cagcatggac tacatcaaaa ccgctaacaa agttgttgaa 1800
gcagggctgt tcgctggttg ggttaaacag atcgttaacg acttcgttat cgaagctaac 1860
aaaagcaaca ctatggacgc aatcgctgac atcagtctga tcgttccgta catcggtctg 1920
gctctgaacg ttggtaacga aaccgctaaa ggtaactttg aaaacgcttt cgagatcgct 1980
ggtgcaagca tcctgctgga gttcatcccg gaactgctga tcccggttgt tggtgctttc 2040
ctgctggaaa gttacatcga caacaaaaac aagatcatca aaaccatcga caacgctctg 2100
accaaacgta acgaaaaatg gagtgatatg tacggtctga tcgttgctca gtggctgagc 2160
accgtcaaca cccagttcta caccatcaaa gaaggtatgt acaaagctct gaactaccag 2220
gctcaggctc tggaagagat catcaaatac cgttacaaca tctacagtga gaaggaaaag 2280
agtaacatca acatcgactt caacgacatc aacagcaaac tgaacgaagg tatcaaccag 2340
gctatcgaca acatcaacaa cttcatcaac ggttgcagtg ttagctacct gatgaagaag 2400
atgatcccgc tggctgttga aaaactgctg gacttcgaca acaccctgaa aaagaacctg 2460
ctgaactaca tcgacgaaaa caagctgtac ctgatcggta gtgctgaata cgaaaaaagt 2520
aaagtgaaca aatacctgaa gaccatcatg ccgttcgacc tgagtatcta caccaacgac 2580
accatcctga tcgaaatgtt caacaaatac aactctctag aataatgaaa gctt 2634
<210> 3
<211> 2620
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 3
ggatccatgc cgatcaccat caacaacttc aactacagcg atccggtgga taacaaaaac 60
atcctgtacc tggataccca tctgaatacc ctggcgaacg aaccggaaaa agcgtttcgt 120
atcaccggca acatttgggt tattccggat cgttttagcc gtaacagcaa cccgaatctg 180
aataaaccgc cgcgtgttac cagcccgaaa agcggttatt acgatccgaa ctatctgagc 240
accgatagcg ataaagatac cttcctgaaa gaaatcatca aactgttcaa acgcatcaac 300
agccgtgaaa ttggcgaaga actgatctat cgcctgagca ccgatattcc gtttccgggc 360
aacaacaaca ccccgatcaa cacctttgat ttcgatgtgg atttcaacag cgttgatgtt 420
aaaacccgcc agggtaacaa ttgggtgaaa accggcagca ttaacccaag cgtgattatt 480
accggtccgc gcgaaaacat tattgatccg gaaaccagca cctttaaact gaccaacaac 540
acctttgcgg cgcaggaagg ttttggcgcg ctgagcatta ttagcattag cccgcgcttt 600
atgctgacct atagcaacgc gaccaacgat gttggtgaag gccgtttcag caaaagcgaa 660
ttttgcatgg acccgatcct gatcctgatg catgaactga accatgcgat gcataacctg 720
tatggcatcg cgattccgaa cgatcagacc attagcagcg tgaccagcaa catcttttac 780
agccagtaca acgtgaaact ggaatatgcg gaaatctatg cgtttggcgg tccgaccatt 840
gatctgattc cgaaaagcgc gcgcaaatac ttcgaagaaa aagcgctgga ttactatcgc 900
agcattgcga aacgtctgaa cagcattacc accgcgaatc cgagcagctt caacaaatat 960
atcggcgaat ataaacagaa actgatccgc aaatatcgct ttgtggtgga aagcagcggc 1020
gaagttaccg ttaaccgcaa taaattcgtg gaactgtaca acgaactgac ccagatcttc 1080
accgaattta actatgcgaa aatctataac gtgcagaacc gtaaaatcta cctgagcaac 1140
gtgtataccc cggtgaccgc gaatattctg gatgataacg tgtacgatat ccagaacggc 1200
tttaacatcc cgaaaagcaa cctgaacgtt ctgtttatgg gccagaacct gagccgtaat 1260
ccggcgctgc gtaaagtgaa cccggaaaac atgctgtacc tgttcaccaa attttgcgtc 1320
gacgcgattg atggtcgtag cctgtacaac aaaaccctgc agtgtcgtga actgctggtg 1380
aaaaacaccg atctgccgtt tattggcgat atcagcgatg tgaaaaccga tatcttcctg 1440
cgcaaagata tcaacgaaga aaccgaagtg atctactacc cggataacgt gagcgttgat 1500
caggtgatcc tgagcaaaaa caccagcgaa catggtcagc tggatctgct gtatccgagc 1560
attgatagcg aaagcgaaat tctgccgggc gaaaaccagg tgttttacga taaccgtacc 1620
cagaacgtgg attacctgaa cagctattac tacctggaaa gccagaaact gagcgataac 1680
gtggaagatt ttacctttac ccgcagcatt gaagaagcgc tggataacag cgcgaaagtt 1740
tacacctatt ttccgaccct ggcgaacaaa gttaatgcgg gtgttcaggg cggtctgttt 1800
ctgatgtggg cgaacgatgt ggtggaagat ttcaccacca acatcctgcg taaagatacc 1860
ctggataaaa tcagcgatgt tagcgcgatt attccgtata ttggtccggc gctgaacatt 1920
agcaatagcg tgcgtcgtgg caattttacc gaagcgtttg cggttaccgg tgtgaccatt 1980
ctgctggaag cgtttccgga atttaccatt ccggcgctgg gtgcgtttgt gatctatagc 2040
aaagtgcagg aacgcaacga aatcatcaaa accatcgata actgcctgga acagcgtatt 2100
aaacgctgga aagatagcta tgaatggatg atgggcacct ggctgagccg tattatcacc 2160
cagttcaaca acatcagcta ccagatgtac gatagcctga actatcaggc gggtgcgatt 2220
aaagcgaaaa tcgatctgga atacaaaaaa tacagcggca gcgataaaga aaacatcaaa 2280
agccaggttg aaaacctgaa aaacagcctg gatgtgaaaa ttagcgaagc gatgaataac 2340
atcaacaaat tcatccgcga atgcagcgtg acctacctgt tcaaaaacat gctgccgaaa 2400
gtgatcgatg aactgaacga atttgatcgc aacaccaaag cgaaactgat caacctgatc 2460
gatagccaca acattattct ggtgggcgaa gtggataaac tgaaagcgaa agttaacaac 2520
agcttccaga acaccatccc gtttaacatc ttcagctata ccaacaacag cctgctgaaa 2580
gatatcatca acgaatactt caatctagac taataagctt 2620
<210> 4
<211> 2638
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 4
ggatccatga cgtggccagt taaggatttc aactactcag atcctgtaaa tgacaacgat 60
attctgtacc ttcgcattcc acaaaataaa ctgatcacca caccagtcaa agcattcatg 120
attactcaaa acatttgggt cattccagaa cgcttttcta gtgacacaaa tccgagttta 180
tctaaacctc cgcgtccgac gtccaaatat cagagctatt acgatccctc atatctcagt 240
acggacgaac aaaaagatac tttccttaaa ggtatcatta aactgtttaa gcgtattaat 300
gagcgcgata tcgggaaaaa gttgattaat tatcttgttg tgggttcccc gttcatgggc 360
gatagctcta cccccgaaga cacttttgat tttacccgtc atacgacaaa catcgcggta 420
gagaagtttg agaacggatc gtggaaagtc acaaacatca ttacacctag cgtcttaatt 480
tttggtccgc tgccaaacat cttagattat acagccagcc tgactttgca ggggcaacag 540
tcgaatccga gtttcgaagg ttttggtacc ctgagcattc tgaaagttgc cccggaattt 600
ctgctcactt tttcagatgt caccagcaac cagagctcag cagtattagg aaagtcaatt 660
ttttgcatgg acccggttat tgcactgatg cacgaactga cgcactctct gcatcaactg 720
tatgggatca acatccccag tgacaaacgt attcgtcccc aggtgtctga aggatttttc 780
tcacaggatg ggccgaacgt ccagttcgaa gagttgtata ctttcggagg cctggacgta 840
gagatcattc cccagattga gcgcagtcag ctgcgtgaga aggcattggg ccattataag 900
gatattgcaa aacgcctgaa taacattaac aaaacgattc catcttcgtg gatctcgaat 960
attgataaat ataagaaaat ttttagcgag aaatataatt ttgataaaga taatacaggt 1020
aactttgtgg ttaacattga caaattcaac tccctttaca gtgatttgac gaatgtaatg 1080
agcgaagttg tgtatagttc ccaatacaac gttaagaatc gtacccatta cttctctcgt 1140
cactacctgc cggttttcgc gaacatcctt gacgataata tttacactat tcgtgacggc 1200
tttaacttga ccaacaaggg cttcaatatt gaaaattcag gccagaacat tgaacgcaac 1260
ccggccttgc agaaactgtc gagtgaatcc gtggttgacc tgtttaccaa agtctgcgtc 1320
gacaaaagcg aagagaagct gtacgatgac gatgacaaag atcgttgggg atcgtccctg 1380
cagtgtatta aagtgaaaaa caatcggctg ccttatgtag cagataaaga tagcattagt 1440
caggagattt tcgaaaataa aattatcact gacgaaacca atgttcagaa ttattcagat 1500
aaattttcac tggacgaaag catcttagat ggccaagttc cgattaaccc ggaaattgtt 1560
gatccgttac tgccgaacgt gaatatggaa ccgttaaacc tccctggcga agagatcgta 1620
ttttatgatg acattacgaa atatgtggac taccttaatt cttattacta tttggaaagc 1680
cagaaactgt ccaataacgt ggaaaacatt actctgacca caagcgtgga agaggcttta 1740
ggctactcaa ataagattta taccttcctc ccgtcgctgg cggaaaaagt aaataaaggt 1800
gtgcaggctg gtctgttcct caactgggcg aatgaagttg tcgaagactt taccacgaat 1860
attatgaaaa aggataccct ggataaaatc tccgacgtct cggttattat cccatatatt 1920
ggccctgcgt taaatatcgg taatagtgcg ctgcggggga attttaacca ggcctttgct 1980
accgcgggcg tcgcgttcct cctggagggc tttcctgaat ttactatccc ggcgctcggt 2040
gtttttacat tttactcttc catccaggag cgtgagaaaa ttatcaaaac catcgaaaac 2100
tgcctggagc agcgggtgaa acgctggaaa gattcttatc aatggatggt gtcaaactgg 2160
ttatctcgca tcacgaccca attcaaccat attaattacc agatgtatga tagtctgtcg 2220
taccaagctg acgccattaa agccaaaatt gatctggaat ataaaaagta ctctggtagc 2280
gataaggaga acatcaaaag ccaggtggag aaccttaaga atagtctgga tgtgaaaatc 2340
tctgaagcta tgaataacat taacaaattc attcgtgaat gttcggtgac gtacctgttc 2400
aagaatatgc tgccaaaagt tattgatgaa ctgaataaat ttgatctgcg taccaaaacc 2460
gaacttatca acctcatcga ctcccacaac attatccttg tgggcgaagt ggatcgtctg 2520
aaggccaaag taaacgagag ctttgaaaat acgatgccgt ttaatatttt ttcatatacc 2580
aataactcct tgctgaaaga tatcatcaat gaatatttca atctagaata ataagctt 2638
<210> 5
<211> 2065
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 5
ggatccatgg agtccaatca gccggaaaaa aatggaaccg cgactaaacc cgagaattcg 60
gggaacacta cgtcggaaaa cggccagacg gaacctgaga agaaactgga actacgaaat 120
gtgtccgata tcgagctata ctctcaaacc aatggaacct ataggcagca tgtttcattg 180
gacggaatcc cagaaaatac ggatacatat ttcgtcaaag tgaagtctag cgcattcaag 240
gatgtatata tccccgttgc gagtattaca gaagagaagc ggaacggtca aagcgtttat 300
aagattacag caaaggccga aaagttacaa caggagttag aaaacaaata cgttgacaat 360
ttcacttttt atctcgataa aaaggctaaa gaggaaaaca cgaacttcac gtcatttagt 420
aatctggtca aagccataaa tcaaaatcca tctggtacat accatctcgc ggcaagtcta 480
aacgcgaatg aagtagaact tggcccggac gagcgttcat acattaagga tacctttact 540
ggcagactca taggggaaaa agacggtaag aactatgcta tatacaattt gaaaaagcct 600
ttatttgaga acctgtcggg cgccaccgtc gagaaattgt cccttaaaaa cgtagctata 660
agcggaaaga atgacatcgg tagtcttgca aacgaggcta ctaacgggac aaagattaaa 720
caagtgcacg tagatgggtg tgtcgacggc atcattacct ccaaaactaa atctgacgat 780
gacgataaaa acaaagcgct gaacctgcag tgcattaaaa taaagaatga ggatttgaca 840
ttcatcgcag aaaaaaatag cttcagcgaa gagccgttcc aagatgagat agtaagctac 900
aacaccaaga acaagccgct taattttaat tactcgttag ataaaatcat agttgactac 960
aaccttcaat cgaagatcac gttaccgaat gacagaacaa ctcctgtcac aaaaggaatt 1020
ccctatgcac ctgagtataa gtcaaatgcc gcgtcaacaa tagagattca taatatagat 1080
gacaacacca tctatcaata tctgtacgct cagaaaagtc caacaactct tcagcgtata 1140
acaatgacca atagtgtcga tgacgcattg ataaattcta ccaagatata ctcttatttc 1200
ccgagcgtca tctccaaagt taatcaaggt gctcaaggca ttctattttt gcaatgggtc 1260
cgagacatca tagatgactt cactaatgag tcgtctcaga aaaccacgat tgataaaata 1320
tcagatgttt ccaccatcgt cccctacatc ggacctgcgc ttaacattgt gaagcagggg 1380
tatgagggga attttatcgg agcgttagaa actacggggg ttgtgctatt acttgaatac 1440
ataccagaga taacattgcc cgttatagcg gccctcagta tcgcagaatc aagtacacaa 1500
aaagaaaaga taatcaaaac aatcgacaac ttcctagaaa agaggtacga aaaatggata 1560
gaggtttata aactcgtgaa agcgaaatgg ttaggcactg ttaatacgca gttccaaaag 1620
agatcctatc aaatgtatag atcactggag taccaggtgg atgccataaa gaaaattatc 1680
gactatgaat ataaaatata ttcaggtcca gataaggagc agatagctga tgaaataaac 1740
aatttaaaaa acaaacttga agagaaggcg aataaggcca tgatcaatat caatattttt 1800
atgcgagaat cttcacgatc ttttttggta aatcagatga ttaacgaagc caaaaagcag 1860
ctgcttgagt tcgacacaca gtccaaaaac atactaatgc aatatatcaa agcaaactca 1920
aaattcattg gaattactga gctgaagaaa ctggaatcca aaataaataa agtattctct 1980
accccgatcc cgttctctta ctctaaaaac cttgactgct gggtagataa cgaagaagat 2040
attgacgttc tagagtaata agctt 2065
<210> 6
<211> 219
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 6
catatgccgg ttggatccat ccaggtcgac tttaaactgc agggtgttac tctagagggc 60
ggtggcggta gcggtggcgg tggcagcggc ggtggcggta gcgcactagt gggcagctca 120
tttctgtctc cggaacatca acgggtgcag cagcgtaaag agagtaaaaa gccgccagcg 180
aaattacagc ctcgctaata gaagcttaag ggcgaattc 219
<210> 7
<211> 2784
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 7
catatgccgg ttggatccat gccgatcacc atcaacaact tcaactacag cgatccggtg 60
gataacaaaa acatcctgta cctggatacc catctgaata ccctggcgaa cgaaccggaa 120
aaagcgtttc gtatcaccgg caacatttgg gttattccgg atcgttttag ccgtaacagc 180
aacccgaatc tgaataaacc gccgcgtgtt accagcccga aaagcggtta ttacgatccg 240
aactatctga gcaccgatag cgataaagat accttcctga aagaaatcat caaactgttc 300
aaacgcatca acagccgtga aattggcgaa gaactgatct atcgcctgag caccgatatt 360
ccgtttccgg gcaacaacaa caccccgatc aacacctttg atttcgatgt ggatttcaac 420
agcgttgatg ttaaaacccg ccagggtaac aattgggtga aaaccggcag cattaacccg 480
agcgtgatta ttaccggtcc gcgcgaaaac attattgatc cggaaaccag cacctttaaa 540
ctgaccaaca acacctttgc ggcgcaggaa ggttttggcg cgctgagcat tattagcatt 600
agcccgcgct ttatgctgac ctatagcaac gcgaccaacg atgttggtga aggccgtttc 660
agcaaaagcg aattttgcat ggacccgatc ctgatcctga tgcatgaact gaaccatgcg 720
atgcataacc tgtatggcat cgcgattccg aacgatcaga ccattagcag cgtgaccagc 780
aacatctttt acagccagta caacgtgaaa ctggaatatg cggaaatcta tgcgtttggc 840
ggtccgacca ttgatctgat tccgaaaagc gcgcgcaaat acttcgaaga aaaagcgctg 900
gattactatc gcagcattgc gaaacgtctg aacagcatta ccaccgcgaa tccgagcagc 960
ttcaacaaat atatcggcga atataaacag aaactgatcc gcaaatatcg ctttgtggtg 1020
gaaagcagcg gcgaagttac cgttaaccgc aataaattcg tggaactgta caacgaactg 1080
acccagatct tcaccgaatt taactatgcg aaaatctata acgtgcagaa ccgtaaaatc 1140
tacctgagca acgtgtatac cccggtgacc gcgaatattc tggatgataa cgtgtacgat 1200
atccagaacg gctttaacat cccgaaaagc aacctgaacg ttctgtttat gggccagaac 1260
ctgagccgta atccggcgct gcgtaaagtg aacccggaaa acatgctgta cctgttcacc 1320
aaattttgcg tcgacgcgat tgatggtcgt agcctgtaca acaaaaccct gcagtgtcgt 1380
gaactgctgg tgaaaaacac cgatctgccg tttattggcg atatcagcga tgtgaaaacc 1440
gatatcttcc tgcgcaaaga tatcaacgaa gaaaccgaag tgatctacta cccggataac 1500
gtgagcgttg atcaggtgat cctgagcaaa aacaccagcg aacatggtca gctggatctg 1560
ctgtatccga gcattgatag cgaaagcgaa attctgccgg gcgaaaacca ggtgttttac 1620
gataaccgta cccagaacgt ggattacctg aacagctatt actacctgga aagccagaaa 1680
ctgagcgata acgtggaaga ttttaccttt acccgcagca ttgaagaagc gctggataac 1740
agcgcgaaag tttacaccta ttttccgacc ctggcgaaca aagttaatgc gggtgttcag 1800
ggcggtctgt ttctgatgtg ggcgaacgat gtggtggaag atttcaccac caacatcctg 1860
cgtaaagata ccctggataa aatcagcgat gttagcgcga ttattccgta tattggtccg 1920
gcgctgaaca ttagcaatag cgtgcgtcgt ggcaatttta ccgaagcgtt tgcggttacc 1980
ggtgtgacca ttctgctgga agcgtttccg gaatttacca ttccggcgct gggtgcgttt 2040
gtgatctata gcaaagtgca ggaacgcaac gaaatcatca aaaccatcga taactgcctg 2100
gaacagcgta ttaaacgctg gaaagatagc tatgaatgga tgatgggcac ctggctgagc 2160
cgtattatca cccagttcaa caacatcagc taccagatgt acgatagcct gaactatcag 2220
gcgggtgcga ttaaagcgaa aatcgatctg gaatacaaaa aatacagcgg cagcgataaa 2280
gaaaacatca aaagccaggt tgaaaacctg aaaaacagcc tggatgtgaa aattagcgaa 2340
gcgatgaata acatcaacaa attcatccgc gaatgcagcg tgacctacct gttcaaaaac 2400
atgctgccga aagtgatcga tgaactgaac gaatttgatc gcaacaccaa agcgaaactg 2460
atcaacctga tcgatagcca caacattatt ctggtgggcg aagtggataa actgaaagcg 2520
aaagttaaca acagcttcca gaacaccatc ccgtttaaca tcttcagcta taccaacaac 2580
agcctgctga aagatatcat caacgaatac ttcaatctag agggcggtgg cggtagcggt 2640
ggcggtggca gcggcggtgg cggtagcgca ctagtgggca gctcatttct gtctccggaa 2700
catcaacggg tgcagcagcg taaagagagt aaaaagccgc cagcgaaatt acagcctcgc 2760
taatagaagc ttaagggcga attc 2784
<210> 8
<211> 913
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 8
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
865 870 875 880
Gly Ser Ala Leu Val Gly Ser Ser Phe Leu Ser Pro Glu His Gln Arg
885 890 895
Val Gln Gln Arg Lys Glu Ser Lys Lys Pro Pro Ala Lys Leu Gln Pro
900 905 910
Arg
<210> 9
<211> 931
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 9
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Tyr Ala Asp Ala Ile
885 890 895
Phe Thr Asn Ser Tyr Arg Lys Val Leu Gly Gln Leu Ser Ala Arg Lys
900 905 910
Leu Leu Gln Asp Ile Met Ser Arg Gln Gln Gly Glu Ser Asn Gln Glu
915 920 925
Arg Gly Ala
930
<210> 10
<211> 944
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 10
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Asn Ser Asp Ser Glu
885 890 895
Cys Pro Leu Ser His Asp Gly Tyr Cys Leu His Asp Gly Val Cys Met
900 905 910
Tyr Ile Glu Ala Leu Asp Lys Tyr Ala Cys Asn Cys Val Val Gly Tyr
915 920 925
Ile Gly Glu Arg Cys Gln Tyr Arg Asp Leu Lys Trp Trp Glu Leu Arg
930 935 940
<210> 11
<211> 1134
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 11
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
885 890 895
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Glu
900 905 910
Pro His Ser Glu Ser Asn Val Pro Ala Gly His Thr Ile Pro Gln Ala
915 920 925
His Trp Thr Lys Leu Gln His Ser Leu Asp Thr Ala Leu Arg Arg Ala
930 935 940
Arg Ser Ala Pro Ala Ala Ala Ile Ala Ala Arg Val Ala Gly Gln Thr
945 950 955 960
Arg Asn Ile Thr Val Asp Pro Arg Leu Phe Lys Lys Arg Arg Leu Arg
965 970 975
Ser Pro Arg Val Leu Phe Ser Thr Gln Pro Pro Arg Glu Ala Ala Asp
980 985 990
Thr Gln Asp Leu Asp Phe Glu Val Gly Gly Ala Ala Pro Phe Asn Arg
995 1000 1005
Thr His Arg Ser Lys Arg Ser Ser Ser His Pro Ile Phe His Arg
1010 1015 1020
Gly Glu Phe Ser Val Cys Asp Ser Val Ser Val Trp Val Gly Asp
1025 1030 1035
Lys Thr Thr Ala Thr Asp Ile Lys Gly Lys Glu Val Met Val Leu
1040 1045 1050
Gly Glu Val Asn Ile Asn Asn Ser Val Phe Lys Gln Tyr Phe Phe
1055 1060 1065
Glu Thr Lys Cys Arg Asp Pro Asn Pro Val Asp Ser Gly Cys Arg
1070 1075 1080
Gly Ile Asp Ser Lys His Trp Asn Ser Tyr Cys Thr Thr Thr His
1085 1090 1095
Thr Phe Val Lys Ala Leu Thr Met Asp Gly Lys Gln Ala Ala Trp
1100 1105 1110
Arg Phe Ile Arg Ile Asp Thr Ala Cys Val Cys Val Leu Ser Arg
1115 1120 1125
Lys Ala Val Arg Arg Ala
1130
<210> 12
<211> 898
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 12
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Ser Cys His Leu Pro
885 890 895
Trp Ala
<210> 13
<211> 919
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 13
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val His Ser Asp Ala Val
885 890 895
Phe Thr Asp Asn Tyr Thr Arg Leu Arg Lys Gln Met Ala Val Lys Lys
900 905 910
Tyr Leu Asn Ser Ile Leu Asn
915
<210> 14
<211> 892
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 14
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
865 870 875 880
Gly Ser Ala Leu Val Ser Cys His Leu Pro Trp Ala
885 890
<210> 15
<211> 955
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 15
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
865 870 875 880
Gly Ser Ala Leu Val Gly Pro Glu Thr Leu Cys Gly Ala Glu Leu Val
885 890 895
Asp Ala Leu Gln Phe Val Cys Gly Asp Arg Gly Phe Tyr Phe Asn Lys
900 905 910
Pro Thr Gly Tyr Gly Ser Ser Ser Arg Arg Ala Pro Gln Thr Gly Ile
915 920 925
Val Asp Glu Cys Cys Phe Arg Ser Cys Asp Leu Arg Arg Leu Glu Met
930 935 940
Tyr Cys Ala Pro Leu Lys Pro Ala Lys Ser Ala
945 950 955
<210> 16
<211> 919
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 16
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
865 870 875 880
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
885 890 895
Ser Gly Gly Gly Gly Ser Ala Leu Val Ala Gly Cys Lys Asn Phe Phe
900 905 910
Trp Lys Thr Phe Thr Ser Cys
915
<210> 17
<211> 919
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 17
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Gly Ser Ser Phe Leu
885 890 895
Ser Pro Glu His Gln Arg Val Gln Gln Arg Lys Glu Ser Lys Lys Pro
900 905 910
Pro Ala Lys Leu Gln Pro Arg
915
<210> 18
<211> 961
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 18
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Gly Pro Glu Thr Leu
885 890 895
Cys Gly Ala Glu Leu Val Asp Ala Leu Gln Phe Val Cys Gly Asp Arg
900 905 910
Gly Phe Tyr Phe Asn Lys Pro Thr Gly Tyr Gly Ser Ser Ser Arg Arg
915 920 925
Ala Pro Gln Thr Gly Ile Val Asp Glu Cys Cys Phe Arg Ser Cys Asp
930 935 940
Leu Arg Arg Leu Glu Met Tyr Cys Ala Pro Leu Lys Pro Ala Lys Ser
945 950 955 960
Ala
<210> 19
<211> 1108
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 19
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
865 870 875 880
Gly Ser Ala Leu Val Glu Pro His Ser Glu Ser Asn Val Pro Ala Gly
885 890 895
His Thr Ile Pro Gln Ala His Trp Thr Lys Leu Gln His Ser Leu Asp
900 905 910
Thr Ala Leu Arg Arg Ala Arg Ser Ala Pro Ala Ala Ala Ile Ala Ala
915 920 925
Arg Val Ala Gly Gln Thr Arg Asn Ile Thr Val Asp Pro Arg Leu Phe
930 935 940
Lys Lys Arg Arg Leu Arg Ser Pro Arg Val Leu Phe Ser Thr Gln Pro
945 950 955 960
Pro Arg Glu Ala Ala Asp Thr Gln Asp Leu Asp Phe Glu Val Gly Gly
965 970 975
Ala Ala Pro Phe Asn Arg Thr His Arg Ser Lys Arg Ser Ser Ser His
980 985 990
Pro Ile Phe His Arg Gly Glu Phe Ser Val Cys Asp Ser Val Ser Val
995 1000 1005
Trp Val Gly Asp Lys Thr Thr Ala Thr Asp Ile Lys Gly Lys Glu
1010 1015 1020
Val Met Val Leu Gly Glu Val Asn Ile Asn Asn Ser Val Phe Lys
1025 1030 1035
Gln Tyr Phe Phe Glu Thr Lys Cys Arg Asp Pro Asn Pro Val Asp
1040 1045 1050
Ser Gly Cys Arg Gly Ile Asp Ser Lys His Trp Asn Ser Tyr Cys
1055 1060 1065
Thr Thr Thr His Thr Phe Val Lys Ala Leu Thr Met Asp Gly Lys
1070 1075 1080
Gln Ala Ala Trp Arg Phe Ile Arg Ile Asp Thr Ala Cys Val Cys
1085 1090 1095
Val Leu Ser Arg Lys Ala Val Arg Arg Ala
1100 1105
<210> 20
<211> 910
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 20
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val
885 890 895
Ala Gly Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys
900 905 910
<210> 21
<211> 913
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 21
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
865 870 875 880
Gly Ser Ala Leu Val His Ser Asp Ala Val Phe Thr Asp Asn Tyr Thr
885 890 895
Arg Leu Arg Lys Gln Met Ala Val Lys Lys Tyr Leu Asn Ser Ile Leu
900 905 910
Asn
<210> 22
<211> 912
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 22
Glu Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly Val
1 5 10 15
Asp Ile Ala Tyr Ile Lys Ile Pro Asn Ala Gly Gln Met Gln Pro Val
20 25 30
Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg Asp
35 40 45
Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu Ala
50 55 60
Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr Asp
65 70 75 80
Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu Arg
85 90 95
Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val Arg
100 105 110
Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys Val
115 120 125
Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr Arg
130 135 140
Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile Ile
145 150 155 160
Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr Arg
165 170 175
Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe Thr
180 185 190
Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu Gly
195 200 205
Ala Gly Lys Phe Ala Thr Asp Pro Ala Val Thr Leu Ala His Glu Leu
210 215 220
Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn Arg
225 230 235 240
Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu Glu
245 250 255
Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys Phe
260 265 270
Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn Lys
275 280 285
Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val Gly
290 295 300
Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys Tyr
305 310 315 320
Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu Lys
325 330 335
Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp Asn
340 345 350
Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn Phe
355 360 365
Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr Thr
370 375 380
Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn Phe
385 390 395 400
Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu Lys
405 410 415
Asn Phe Thr Gly Leu Phe Glu Phe Tyr Lys Leu Leu Cys Val Asp Gly
420 425 430
Ile Ile Thr Ser Lys Thr Lys Ser Asp Asp Asp Asp Lys Asn Lys Ala
435 440 445
Leu Asn Leu Gln Cys Ile Lys Val Asn Asn Trp Asp Leu Phe Phe Ser
450 455 460
Pro Ser Glu Asp Asn Phe Thr Asn Asp Leu Asn Lys Gly Glu Glu Ile
465 470 475 480
Thr Ser Asp Thr Asn Ile Glu Ala Ala Glu Glu Asn Ile Ser Leu Asp
485 490 495
Leu Ile Gln Gln Tyr Tyr Leu Thr Phe Asn Phe Asp Asn Glu Pro Glu
500 505 510
Asn Ile Ser Ile Glu Asn Leu Ser Ser Asp Ile Ile Gly Gln Leu Glu
515 520 525
Leu Met Pro Asn Ile Glu Arg Phe Pro Asn Gly Lys Lys Tyr Glu Leu
530 535 540
Asp Lys Tyr Thr Met Phe His Tyr Leu Arg Ala Gln Glu Phe Glu His
545 550 555 560
Gly Lys Ser Arg Ile Ala Leu Thr Asn Ser Val Asn Glu Ala Leu Leu
565 570 575
Asn Pro Ser Arg Val Tyr Thr Phe Phe Ser Ser Asp Tyr Val Lys Lys
580 585 590
Val Asn Lys Ala Thr Glu Ala Ala Met Phe Leu Gly Trp Val Glu Gln
595 600 605
Leu Val Tyr Asp Phe Thr Asp Glu Thr Ser Glu Val Ser Thr Thr Asp
610 615 620
Lys Ile Ala Asp Ile Thr Ile Ile Ile Pro Tyr Ile Gly Pro Ala Leu
625 630 635 640
Asn Ile Gly Asn Met Leu Tyr Lys Asp Asp Phe Val Gly Ala Leu Ile
645 650 655
Phe Ser Gly Ala Val Ile Leu Leu Glu Phe Ile Pro Glu Ile Ala Ile
660 665 670
Pro Val Leu Gly Thr Phe Ala Leu Val Ser Tyr Ile Ala Asn Lys Val
675 680 685
Leu Thr Val Gln Thr Ile Asp Asn Ala Leu Ser Lys Arg Asn Glu Lys
690 695 700
Trp Asp Glu Val Tyr Lys Tyr Ile Val Thr Asn Trp Leu Ala Lys Val
705 710 715 720
Asn Thr Gln Ile Asp Leu Ile Arg Lys Lys Met Lys Glu Ala Leu Glu
725 730 735
Asn Gln Ala Glu Ala Thr Lys Ala Ile Ile Asn Tyr Gln Tyr Asn Gln
740 745 750
Tyr Thr Glu Glu Glu Lys Asn Asn Ile Asn Phe Asn Ile Asp Asp Leu
755 760 765
Ser Ser Lys Leu Asn Glu Ser Ile Asn Lys Ala Met Ile Asn Ile Asn
770 775 780
Lys Phe Leu Asn Gln Cys Ser Val Ser Tyr Leu Met Asn Ser Met Ile
785 790 795 800
Pro Tyr Gly Val Lys Arg Leu Glu Asp Phe Asp Ala Ser Leu Lys Asp
805 810 815
Ala Leu Leu Lys Tyr Ile Tyr Asp Asn Arg Gly Thr Leu Ile Gly Gln
820 825 830
Val Asp Arg Leu Lys Asp Lys Val Asn Asn Thr Leu Ser Thr Asp Ile
835 840 845
Pro Phe Gln Leu Ser Lys Tyr Val Asp Asn Gln Arg Leu Leu Ser Thr
850 855 860
Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
865 870 875 880
Ser Ala Leu Val Gly Ser Ser Phe Leu Ser Pro Glu His Gln Arg Val
885 890 895
Gln Gln Arg Lys Glu Ser Lys Lys Pro Pro Ala Lys Leu Gln Pro Arg
900 905 910
<210> 23
<211> 916
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 23
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Ile
435 440 445
Glu Gly Arg Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Asn Val
450 455 460
Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Ser Arg
465 470 475 480
Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
485 490 495
Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu
500 505 510
Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn
515 520 525
Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe
530 535 540
Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu
545 550 555 560
Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu
565 570 575
Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp
580 585 590
Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn
595 600 605
Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr
610 615 620
Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn
625 630 635 640
Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val
645 650 655
Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile
660 665 670
Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile
675 680 685
Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala
690 695 700
Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala
705 710 715 720
Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile
725 730 735
Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys
740 745 750
Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr
755 760 765
Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln
770 775 780
Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser
785 790 795 800
Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn
805 810 815
Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe
820 825 830
Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys
835 840 845
Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu
850 855 860
Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp
865 870 875 880
Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe
885 890 895
Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn
900 905 910
Glu Tyr Phe Asn
915
<210> 24
<211> 910
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 24
His Val Asp Ala Ile Phe Thr Gln Ser Tyr Arg Lys Val Leu Ala Gln
1 5 10 15
Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Asn Arg Asn Asn Asn
20 25 30
Asn Asn Asn Asn Asn Asn Asn Thr Trp Pro Val Lys Asp Phe Asn Tyr
35 40 45
Ser Asp Pro Val Asn Asp Asn Asp Ile Leu Tyr Leu Arg Ile Pro Gln
50 55 60
Asn Lys Leu Ile Thr Thr Pro Val Lys Ala Phe Met Ile Thr Gln Asn
65 70 75 80
Ile Trp Val Ile Pro Glu Arg Phe Ser Ser Asp Thr Asn Pro Ser Leu
85 90 95
Ser Lys Pro Pro Arg Pro Thr Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro
100 105 110
Ser Tyr Leu Ser Thr Asp Glu Gln Lys Asp Thr Phe Leu Lys Gly Ile
115 120 125
Ile Lys Leu Phe Lys Arg Ile Asn Glu Arg Asp Ile Gly Lys Lys Leu
130 135 140
Ile Asn Tyr Leu Val Val Gly Ser Pro Phe Met Gly Asp Ser Ser Thr
145 150 155 160
Pro Glu Asp Thr Phe Asp Phe Thr Arg His Thr Thr Asn Ile Ala Val
165 170 175
Glu Lys Phe Glu Asn Gly Ser Trp Lys Val Thr Asn Ile Ile Thr Pro
180 185 190
Ser Val Leu Ile Phe Gly Pro Leu Pro Asn Ile Leu Asp Tyr Thr Ala
195 200 205
Ser Leu Thr Leu Gln Gly Gln Gln Ser Asn Pro Ser Phe Glu Gly Phe
210 215 220
Gly Thr Leu Ser Ile Leu Lys Val Ala Pro Glu Phe Leu Leu Thr Phe
225 230 235 240
Ser Asp Val Thr Ser Asn Gln Ser Ser Ala Val Leu Gly Lys Ser Ile
245 250 255
Phe Cys Met Asp Pro Val Ile Ala Leu Met His Glu Leu Thr His Ser
260 265 270
Leu His Gln Leu Tyr Gly Ile Asn Ile Pro Ser Asp Lys Arg Ile Arg
275 280 285
Pro Gln Val Ser Glu Gly Phe Phe Ser Gln Asp Gly Pro Asn Val Gln
290 295 300
Phe Glu Glu Leu Tyr Thr Phe Gly Gly Leu Asp Val Glu Ile Ile Pro
305 310 315 320
Gln Ile Glu Arg Ser Gln Leu Arg Glu Lys Ala Leu Gly His Tyr Lys
325 330 335
Asp Ile Ala Lys Arg Leu Asn Asn Ile Asn Lys Thr Ile Pro Ser Ser
340 345 350
Trp Ile Ser Asn Ile Asp Lys Tyr Lys Lys Ile Phe Ser Glu Lys Tyr
355 360 365
Asn Phe Asp Lys Asp Asn Thr Gly Asn Phe Val Val Asn Ile Asp Lys
370 375 380
Phe Asn Ser Leu Tyr Ser Asp Leu Thr Asn Val Met Ser Glu Val Val
385 390 395 400
Tyr Ser Ser Gln Tyr Asn Val Lys Asn Arg Thr His Tyr Phe Ser Arg
405 410 415
His Tyr Leu Pro Val Phe Ala Asn Ile Leu Asp Asp Asn Ile Tyr Thr
420 425 430
Ile Arg Asp Gly Phe Asn Leu Thr Asn Lys Gly Phe Asn Ile Glu Asn
435 440 445
Ser Gly Gln Asn Ile Glu Arg Asn Pro Ala Leu Gln Lys Leu Ser Ser
450 455 460
Glu Ser Val Val Asp Leu Phe Thr Lys Val Cys Val Asp Lys Ser Glu
465 470 475 480
Glu Lys Leu Tyr Asp Asp Asp Asp Lys Asp Arg Trp Gly Ser Ser Leu
485 490 495
Gln Cys Ile Lys Val Lys Asn Asn Arg Leu Pro Tyr Val Ala Asp Lys
500 505 510
Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys Ile Ile Thr Asp Glu
515 520 525
Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser Leu Asp Glu Ser Ile
530 535 540
Leu Asp Gly Gln Val Pro Ile Asn Pro Glu Ile Val Asp Pro Leu Leu
545 550 555 560
Pro Asn Val Asn Met Glu Pro Leu Asn Leu Pro Gly Glu Glu Ile Val
565 570 575
Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr
580 585 590
Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn Val Glu Asn Ile Thr Leu
595 600 605
Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser Asn Lys Ile Tyr Thr
610 615 620
Phe Leu Pro Ser Leu Ala Glu Lys Val Asn Lys Gly Val Gln Ala Gly
625 630 635 640
Leu Phe Leu Asn Trp Ala Asn Glu Val Val Glu Asp Phe Thr Thr Asn
645 650 655
Ile Met Lys Lys Asp Thr Leu Asp Lys Ile Ser Asp Val Ser Val Ile
660 665 670
Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Ser Ala Leu Arg
675 680 685
Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly Val Ala Phe Leu Leu
690 695 700
Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Val Phe Thr Phe
705 710 715 720
Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile Lys Thr Ile Glu Asn
725 730 735
Cys Leu Glu Gln Arg Val Lys Arg Trp Lys Asp Ser Tyr Gln Trp Met
740 745 750
Val Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln Phe Asn His Ile Asn
755 760 765
Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala Asp Ala Ile Lys Ala
770 775 780
Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp Lys Glu Asn
785 790 795 800
Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp Val Lys Ile
805 810 815
Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu Cys Ser Val
820 825 830
Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp Glu Leu Asn
835 840 845
Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile Asn Leu Ile Asp Ser
850 855 860
His Asn Ile Ile Leu Val Gly Glu Val Asp Arg Leu Lys Ala Lys Val
865 870 875 880
Asn Glu Ser Phe Glu Asn Thr Met Pro Phe Asn Ile Phe Ser Tyr Thr
885 890 895
Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe Asn
900 905 910
<210> 25
<211> 714
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 25
Glu Ser Asn Gln Pro Glu Lys Asn Gly Thr Ala Thr Lys Pro Glu Asn
1 5 10 15
Ser Gly Asn Thr Thr Ser Glu Asn Gly Gln Thr Glu Pro Glu Lys Lys
20 25 30
Leu Glu Leu Arg Asn Val Ser Asp Ile Glu Leu Tyr Ser Gln Thr Asn
35 40 45
Gly Thr Tyr Arg Gln His Val Ser Leu Asp Gly Ile Pro Glu Asn Thr
50 55 60
Asp Thr Tyr Phe Val Lys Val Lys Ser Ser Ala Phe Lys Asp Val Tyr
65 70 75 80
Ile Pro Val Ala Ser Ile Thr Glu Glu Lys Arg Asn Gly Gln Ser Val
85 90 95
Tyr Lys Ile Thr Ala Lys Ala Glu Lys Leu Gln Gln Glu Leu Glu Asn
100 105 110
Lys Tyr Val Asp Asn Phe Thr Phe Tyr Leu Asp Lys Lys Ala Lys Glu
115 120 125
Glu Asn Thr Asn Phe Thr Ser Phe Ser Asn Leu Val Lys Ala Ile Asn
130 135 140
Gln Asn Pro Ser Gly Thr Tyr His Leu Ala Ala Ser Leu Asn Ala Asn
145 150 155 160
Glu Val Glu Leu Gly Pro Asp Glu Arg Ser Tyr Ile Lys Asp Thr Phe
165 170 175
Thr Gly Arg Leu Ile Gly Glu Lys Asp Gly Lys Asn Tyr Ala Ile Tyr
180 185 190
Asn Leu Lys Lys Pro Leu Phe Glu Asn Leu Ser Gly Ala Thr Val Glu
195 200 205
Lys Leu Ser Leu Lys Asn Val Ala Ile Ser Gly Lys Asn Asp Ile Gly
210 215 220
Ser Leu Ala Asn Glu Ala Thr Asn Gly Thr Lys Ile Lys Gln Val His
225 230 235 240
Val Asp Gly Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
245 250 255
Asp Asp Asp Lys Asn Lys Ala Leu Asn Leu Gln Cys Ile Lys Ile Lys
260 265 270
Asn Glu Asp Leu Thr Phe Ile Ala Glu Lys Asn Ser Phe Ser Glu Glu
275 280 285
Pro Phe Gln Asp Glu Ile Val Ser Tyr Asn Thr Lys Asn Lys Pro Leu
290 295 300
Asn Phe Asn Tyr Ser Leu Asp Lys Ile Ile Val Asp Tyr Asn Leu Gln
305 310 315 320
Ser Lys Ile Thr Leu Pro Asn Asp Arg Thr Thr Pro Val Thr Lys Gly
325 330 335
Ile Pro Tyr Ala Pro Glu Tyr Lys Ser Asn Ala Ala Ser Thr Ile Glu
340 345 350
Ile His Asn Ile Asp Asp Asn Thr Ile Tyr Gln Tyr Leu Tyr Ala Gln
355 360 365
Lys Ser Pro Thr Thr Leu Gln Arg Ile Thr Met Thr Asn Ser Val Asp
370 375 380
Asp Ala Leu Ile Asn Ser Thr Lys Ile Tyr Ser Tyr Phe Pro Ser Val
385 390 395 400
Ile Ser Lys Val Asn Gln Gly Ala Gln Gly Ile Leu Phe Leu Gln Trp
405 410 415
Val Arg Asp Ile Ile Asp Asp Phe Thr Asn Glu Ser Ser Gln Lys Thr
420 425 430
Thr Ile Asp Lys Ile Ser Asp Val Ser Thr Ile Val Pro Tyr Ile Gly
435 440 445
Pro Ala Leu Asn Ile Val Lys Gln Gly Tyr Glu Gly Asn Phe Ile Gly
450 455 460
Ala Leu Glu Thr Thr Gly Val Val Leu Leu Leu Glu Tyr Ile Pro Glu
465 470 475 480
Ile Thr Leu Pro Val Ile Ala Ala Leu Ser Ile Ala Glu Ser Ser Thr
485 490 495
Gln Lys Glu Lys Ile Ile Lys Thr Ile Asp Asn Phe Leu Glu Lys Arg
500 505 510
Tyr Glu Lys Trp Ile Glu Val Tyr Lys Leu Val Lys Ala Lys Trp Leu
515 520 525
Gly Thr Val Asn Thr Gln Phe Gln Lys Arg Ser Tyr Gln Met Tyr Arg
530 535 540
Ser Leu Glu Tyr Gln Val Asp Ala Ile Lys Lys Ile Ile Asp Tyr Glu
545 550 555 560
Tyr Lys Ile Tyr Ser Gly Pro Asp Lys Glu Gln Ile Ala Asp Glu Ile
565 570 575
Asn Asn Leu Lys Asn Lys Leu Glu Glu Lys Ala Asn Lys Ala Met Ile
580 585 590
Asn Ile Asn Ile Phe Met Arg Glu Ser Ser Arg Ser Phe Leu Val Asn
595 600 605
Gln Met Ile Asn Glu Ala Lys Lys Gln Leu Leu Glu Phe Asp Thr Gln
610 615 620
Ser Lys Asn Ile Leu Met Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile
625 630 635 640
Gly Ile Thr Glu Leu Lys Lys Leu Glu Ser Lys Ile Asn Lys Val Phe
645 650 655
Ser Thr Pro Ile Pro Phe Ser Tyr Ser Lys Asn Leu Asp Cys Trp Val
660 665 670
Asp Asn Glu Glu Asp Ile Asp Val Leu Glu Gly Gly Gly Gly Ser Gly
675 680 685
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Ala Gly Cys Lys
690 695 700
Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys
705 710
<210> 26
<211> 728
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 26
Glu Ser Asn Gln Pro Glu Lys Asn Gly Thr Ala Thr Lys Pro Glu Asn
1 5 10 15
Ser Gly Asn Thr Thr Ser Glu Asn Gly Gln Thr Glu Pro Glu Lys Lys
20 25 30
Leu Glu Leu Arg Asn Val Ser Asp Ile Glu Leu Tyr Ser Gln Thr Asn
35 40 45
Gly Thr Tyr Arg Gln His Val Ser Leu Asp Gly Ile Pro Glu Asn Thr
50 55 60
Asp Thr Tyr Phe Val Lys Val Lys Ser Ser Ala Phe Lys Asp Val Tyr
65 70 75 80
Ile Pro Val Ala Ser Ile Thr Glu Glu Lys Arg Asn Gly Gln Ser Val
85 90 95
Tyr Lys Ile Thr Ala Lys Ala Glu Lys Leu Gln Gln Glu Leu Glu Asn
100 105 110
Lys Tyr Val Asp Asn Phe Thr Phe Tyr Leu Asp Lys Lys Ala Lys Glu
115 120 125
Glu Asn Thr Asn Phe Thr Ser Phe Ser Asn Leu Val Lys Ala Ile Asn
130 135 140
Gln Asn Pro Ser Gly Thr Tyr His Leu Ala Ala Ser Leu Asn Ala Asn
145 150 155 160
Glu Val Glu Leu Gly Pro Asp Glu Arg Ser Tyr Ile Lys Asp Thr Phe
165 170 175
Thr Gly Arg Leu Ile Gly Glu Lys Asp Gly Lys Asn Tyr Ala Ile Tyr
180 185 190
Asn Leu Lys Lys Pro Leu Phe Glu Asn Leu Ser Gly Ala Thr Val Glu
195 200 205
Lys Leu Ser Leu Lys Asn Val Ala Ile Ser Gly Lys Asn Asp Ile Gly
210 215 220
Ser Leu Ala Asn Glu Ala Thr Asn Gly Thr Lys Ile Lys Gln Val His
225 230 235 240
Val Asp Gly Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
245 250 255
Asp Asp Asp Lys Asn Lys Ala Leu Asn Leu Gln Cys Ile Lys Ile Lys
260 265 270
Asn Glu Asp Leu Thr Phe Ile Ala Glu Lys Asn Ser Phe Ser Glu Glu
275 280 285
Pro Phe Gln Asp Glu Ile Val Ser Tyr Asn Thr Lys Asn Lys Pro Leu
290 295 300
Asn Phe Asn Tyr Ser Leu Asp Lys Ile Ile Val Asp Tyr Asn Leu Gln
305 310 315 320
Ser Lys Ile Thr Leu Pro Asn Asp Arg Thr Thr Pro Val Thr Lys Gly
325 330 335
Ile Pro Tyr Ala Pro Glu Tyr Lys Ser Asn Ala Ala Ser Thr Ile Glu
340 345 350
Ile His Asn Ile Asp Asp Asn Thr Ile Tyr Gln Tyr Leu Tyr Ala Gln
355 360 365
Lys Ser Pro Thr Thr Leu Gln Arg Ile Thr Met Thr Asn Ser Val Asp
370 375 380
Asp Ala Leu Ile Asn Ser Thr Lys Ile Tyr Ser Tyr Phe Pro Ser Val
385 390 395 400
Ile Ser Lys Val Asn Gln Gly Ala Gln Gly Ile Leu Phe Leu Gln Trp
405 410 415
Val Arg Asp Ile Ile Asp Asp Phe Thr Asn Glu Ser Ser Gln Lys Thr
420 425 430
Thr Ile Asp Lys Ile Ser Asp Val Ser Thr Ile Val Pro Tyr Ile Gly
435 440 445
Pro Ala Leu Asn Ile Val Lys Gln Gly Tyr Glu Gly Asn Phe Ile Gly
450 455 460
Ala Leu Glu Thr Thr Gly Val Val Leu Leu Leu Glu Tyr Ile Pro Glu
465 470 475 480
Ile Thr Leu Pro Val Ile Ala Ala Leu Ser Ile Ala Glu Ser Ser Thr
485 490 495
Gln Lys Glu Lys Ile Ile Lys Thr Ile Asp Asn Phe Leu Glu Lys Arg
500 505 510
Tyr Glu Lys Trp Ile Glu Val Tyr Lys Leu Val Lys Ala Lys Trp Leu
515 520 525
Gly Thr Val Asn Thr Gln Phe Gln Lys Arg Ser Tyr Gln Met Tyr Arg
530 535 540
Ser Leu Glu Tyr Gln Val Asp Ala Ile Lys Lys Ile Ile Asp Tyr Glu
545 550 555 560
Tyr Lys Ile Tyr Ser Gly Pro Asp Lys Glu Gln Ile Ala Asp Glu Ile
565 570 575
Asn Asn Leu Lys Asn Lys Leu Glu Glu Lys Ala Asn Lys Ala Met Ile
580 585 590
Asn Ile Asn Ile Phe Met Arg Glu Ser Ser Arg Ser Phe Leu Val Asn
595 600 605
Gln Met Ile Asn Glu Ala Lys Lys Gln Leu Leu Glu Phe Asp Thr Gln
610 615 620
Ser Lys Asn Ile Leu Met Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile
625 630 635 640
Gly Ile Thr Glu Leu Lys Lys Leu Glu Ser Lys Ile Asn Lys Val Phe
645 650 655
Ser Thr Pro Ile Pro Phe Ser Tyr Ser Lys Asn Leu Asp Cys Trp Val
660 665 670
Asp Asn Glu Glu Asp Ile Asp Val Leu Glu Gly Gly Gly Gly Ser Gly
675 680 685
Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Gly Ser Ser Phe
690 695 700
Leu Ser Pro Glu His Gln Arg Val Gln Gln Arg Lys Glu Ser Lys Lys
705 710 715 720
Pro Pro Ala Lys Leu Gln Pro Arg
725
<210> 27
<211> 899
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 27
Glu Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly Val
1 5 10 15
Asp Ile Ala Tyr Ile Lys Ile Pro Asn Ala Gly Gln Met Gln Pro Val
20 25 30
Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg Asp
35 40 45
Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu Ala
50 55 60
Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr Asp
65 70 75 80
Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu Arg
85 90 95
Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val Arg
100 105 110
Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys Val
115 120 125
Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr Arg
130 135 140
Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile Ile
145 150 155 160
Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr Arg
165 170 175
Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe Thr
180 185 190
Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu Gly
195 200 205
Ala Gly Lys Phe Ala Thr Asp Pro Ala Val Thr Leu Ala His Glu Leu
210 215 220
Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn Arg
225 230 235 240
Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu Glu
245 250 255
Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys Phe
260 265 270
Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn Lys
275 280 285
Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val Gly
290 295 300
Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys Tyr
305 310 315 320
Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu Lys
325 330 335
Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp Asn
340 345 350
Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn Phe
355 360 365
Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr Thr
370 375 380
Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn Phe
385 390 395 400
Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu Lys
405 410 415
Asn Phe Thr Gly Leu Phe Glu Phe Tyr Lys Leu Leu Cys Val Asp Gly
420 425 430
Ile Ile Thr Ser Lys Thr Lys Ser Asp Asp Asp Asp Lys Asn Lys Ala
435 440 445
Leu Asn Leu Gln Cys Ile Lys Val Asn Asn Trp Asp Leu Phe Phe Ser
450 455 460
Pro Ser Glu Asp Asn Phe Thr Asn Asp Leu Asn Lys Gly Glu Glu Ile
465 470 475 480
Thr Ser Asp Thr Asn Ile Glu Ala Ala Glu Glu Asn Ile Ser Leu Asp
485 490 495
Leu Ile Gln Gln Tyr Tyr Leu Thr Phe Asn Phe Asp Asn Glu Pro Glu
500 505 510
Asn Ile Ser Ile Glu Asn Leu Ser Ser Asp Ile Ile Gly Gln Leu Glu
515 520 525
Leu Met Pro Asn Ile Glu Arg Phe Pro Asn Gly Lys Lys Tyr Glu Leu
530 535 540
Asp Lys Tyr Thr Met Phe His Tyr Leu Arg Ala Gln Glu Phe Glu His
545 550 555 560
Gly Lys Ser Arg Ile Ala Leu Thr Asn Ser Val Asn Glu Ala Leu Leu
565 570 575
Asn Pro Ser Arg Val Tyr Thr Phe Phe Ser Ser Asp Tyr Val Lys Lys
580 585 590
Val Asn Lys Ala Thr Glu Ala Ala Met Phe Leu Gly Trp Val Glu Gln
595 600 605
Leu Val Tyr Asp Phe Thr Asp Glu Thr Ser Glu Val Ser Thr Thr Asp
610 615 620
Lys Ile Ala Asp Ile Thr Ile Ile Ile Pro Tyr Ile Gly Pro Ala Leu
625 630 635 640
Asn Ile Gly Asn Met Leu Tyr Lys Asp Asp Phe Val Gly Ala Leu Ile
645 650 655
Phe Ser Gly Ala Val Ile Leu Leu Glu Phe Ile Pro Glu Ile Ala Ile
660 665 670
Pro Val Leu Gly Thr Phe Ala Leu Val Ser Tyr Ile Ala Asn Lys Val
675 680 685
Leu Thr Val Gln Thr Ile Asp Asn Ala Leu Ser Lys Arg Asn Glu Lys
690 695 700
Trp Asp Glu Val Tyr Lys Tyr Ile Val Thr Asn Trp Leu Ala Lys Val
705 710 715 720
Asn Thr Gln Ile Asp Leu Ile Arg Lys Lys Met Lys Glu Ala Leu Glu
725 730 735
Asn Gln Ala Glu Ala Thr Lys Ala Ile Ile Asn Tyr Gln Tyr Asn Gln
740 745 750
Tyr Thr Glu Glu Glu Lys Asn Asn Ile Asn Phe Asn Ile Asp Asp Leu
755 760 765
Ser Ser Lys Leu Asn Glu Ser Ile Asn Lys Ala Met Ile Asn Ile Asn
770 775 780
Lys Phe Leu Asn Gln Cys Ser Val Ser Tyr Leu Met Asn Ser Met Ile
785 790 795 800
Pro Tyr Gly Val Lys Arg Leu Glu Asp Phe Asp Ala Ser Leu Lys Asp
805 810 815
Ala Leu Leu Lys Tyr Ile Tyr Asp Asn Arg Gly Thr Leu Ile Gly Gln
820 825 830
Val Asp Arg Leu Lys Asp Lys Val Asn Asn Thr Leu Ser Thr Asp Ile
835 840 845
Pro Phe Gln Leu Ser Lys Tyr Val Asp Asn Gln Arg Leu Leu Ser Thr
850 855 860
Leu Glu Ile Tyr Ala Leu Val Gly Ser Trp Phe Leu Ser Pro Glu His
865 870 875 880
Gln Arg Val Gln Gln Arg Lys Glu Ser Lys Lys Pro Pro Ala Lys Leu
885 890 895
Gln Pro Arg
<210> 28
<211> 929
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 28
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
885 890 895
Gly Ser Ala Leu Val Ser Ala Asn Ser Asn Pro Ala Met Ala Pro Arg
900 905 910
Glu Arg Lys Ala Gly Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser
915 920 925
Cys
<210> 29
<211> 901
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 29
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Gly Asn His Trp Ala
885 890 895
Val Gly His Leu Met
900
<210> 30
<211> 899
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 30
Pro Val Thr Ile Asn Asn Phe Asn Tyr Asn Asp Pro Ile Asp Asn Asn
1 5 10 15
Asn Ile Ile Met Met Glu Pro Pro Phe Ala Arg Gly Thr Gly Arg Tyr
20 25 30
Tyr Lys Ala Phe Lys Ile Thr Asp Arg Ile Trp Ile Ile Pro Glu Arg
35 40 45
Tyr Thr Phe Gly Tyr Lys Pro Glu Asp Phe Asn Lys Ser Ser Gly Ile
50 55 60
Phe Asn Arg Asp Val Cys Glu Tyr Tyr Asp Pro Asp Tyr Leu Asn Thr
65 70 75 80
Asn Asp Lys Lys Asn Ile Phe Leu Gln Thr Met Ile Lys Leu Phe Asn
85 90 95
Arg Ile Lys Ser Lys Pro Leu Gly Glu Lys Leu Leu Glu Met Ile Ile
100 105 110
Asn Gly Ile Pro Tyr Leu Gly Asp Arg Arg Val Pro Leu Glu Glu Phe
115 120 125
Asn Thr Asn Ile Ala Ser Val Thr Val Asn Lys Leu Ile Ser Asn Pro
130 135 140
Gly Glu Val Glu Arg Lys Lys Gly Ile Phe Ala Asn Leu Ile Ile Phe
145 150 155 160
Gly Pro Gly Pro Val Leu Asn Glu Asn Glu Thr Ile Asp Ile Gly Ile
165 170 175
Gln Asn His Phe Ala Ser Arg Glu Gly Phe Gly Gly Ile Met Gln Met
180 185 190
Lys Phe Cys Pro Glu Tyr Val Ser Val Phe Asn Asn Val Gln Glu Asn
195 200 205
Lys Gly Ala Ser Ile Phe Asn Arg Arg Gly Tyr Phe Ser Asp Pro Ala
210 215 220
Leu Ile Leu Met His Glu Leu Ile His Val Leu His Gly Leu Tyr Gly
225 230 235 240
Ile Lys Val Asp Asp Leu Pro Ile Val Pro Asn Glu Lys Lys Phe Phe
245 250 255
Met Gln Ser Thr Asp Ala Ile Gln Ala Glu Glu Leu Tyr Thr Phe Gly
260 265 270
Gly Gln Asp Pro Ser Ile Ile Thr Pro Ser Thr Asp Lys Ser Ile Tyr
275 280 285
Asp Lys Val Leu Gln Asn Phe Arg Gly Ile Val Asp Arg Leu Asn Lys
290 295 300
Val Leu Val Cys Ile Ser Asp Pro Asn Ile Asn Ile Asn Ile Tyr Lys
305 310 315 320
Asn Lys Phe Lys Asp Lys Tyr Lys Phe Val Glu Asp Ser Glu Gly Lys
325 330 335
Tyr Ser Ile Asp Val Glu Ser Phe Asp Lys Leu Tyr Lys Ser Leu Met
340 345 350
Phe Gly Phe Thr Glu Thr Asn Ile Ala Glu Asn Tyr Lys Ile Lys Thr
355 360 365
Arg Ala Ser Tyr Phe Ser Asp Ser Leu Pro Pro Val Lys Ile Lys Asn
370 375 380
Leu Leu Asp Asn Glu Ile Tyr Thr Ile Glu Glu Gly Phe Asn Ile Ser
385 390 395 400
Asp Lys Asp Met Glu Lys Glu Tyr Arg Gly Gln Asn Lys Ala Ile Asn
405 410 415
Lys Gln Ala Tyr Glu Glu Ile Ser Lys Glu His Leu Ala Val Tyr Lys
420 425 430
Ile Gln Met Cys Val Asp Glu Glu Lys Leu Tyr Asp Asp Asp Asp Lys
435 440 445
Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Asp Val Asp Asn Glu Asp
450 455 460
Leu Phe Phe Ile Ala Asp Lys Asn Ser Phe Ser Asp Asp Leu Ser Lys
465 470 475 480
Asn Glu Arg Ile Glu Tyr Asn Thr Gln Ser Asn Tyr Ile Glu Asn Asp
485 490 495
Phe Pro Ile Asn Glu Leu Ile Leu Asp Thr Asp Leu Ile Ser Lys Ile
500 505 510
Glu Leu Pro Ser Glu Asn Thr Glu Ser Leu Thr Asp Phe Asn Val Asp
515 520 525
Val Pro Val Tyr Glu Lys Gln Pro Ala Ile Lys Lys Ile Phe Thr Asp
530 535 540
Glu Asn Thr Ile Phe Gln Tyr Leu Tyr Ser Gln Thr Phe Pro Leu Asp
545 550 555 560
Ile Arg Asp Ile Ser Leu Thr Ser Ser Phe Asp Asp Ala Leu Leu Phe
565 570 575
Ser Asn Lys Val Tyr Ser Phe Phe Ser Met Asp Tyr Ile Lys Thr Ala
580 585 590
Asn Lys Val Val Glu Ala Gly Leu Phe Ala Gly Trp Val Lys Gln Ile
595 600 605
Val Asn Asp Phe Val Ile Glu Ala Asn Lys Ser Asn Thr Met Asp Ala
610 615 620
Ile Ala Asp Ile Ser Leu Ile Val Pro Tyr Ile Gly Leu Ala Leu Asn
625 630 635 640
Val Gly Asn Glu Thr Ala Lys Gly Asn Phe Glu Asn Ala Phe Glu Ile
645 650 655
Ala Gly Ala Ser Ile Leu Leu Glu Phe Ile Pro Glu Leu Leu Ile Pro
660 665 670
Val Val Gly Ala Phe Leu Leu Glu Ser Tyr Ile Asp Asn Lys Asn Lys
675 680 685
Ile Ile Lys Thr Ile Asp Asn Ala Leu Thr Lys Arg Asn Glu Lys Trp
690 695 700
Ser Asp Met Tyr Gly Leu Ile Val Ala Gln Trp Leu Ser Thr Val Asn
705 710 715 720
Thr Gln Phe Tyr Thr Ile Lys Glu Gly Met Tyr Lys Ala Leu Asn Tyr
725 730 735
Gln Ala Gln Ala Leu Glu Glu Ile Ile Lys Tyr Arg Tyr Asn Ile Tyr
740 745 750
Ser Glu Lys Glu Lys Ser Asn Ile Asn Ile Asp Phe Asn Asp Ile Asn
755 760 765
Ser Lys Leu Asn Glu Gly Ile Asn Gln Ala Ile Asp Asn Ile Asn Asn
770 775 780
Phe Ile Asn Gly Cys Ser Val Ser Tyr Leu Met Lys Lys Met Ile Pro
785 790 795 800
Leu Ala Val Glu Lys Leu Leu Asp Phe Asp Asn Thr Leu Lys Lys Asn
805 810 815
Leu Leu Asn Tyr Ile Asp Glu Asn Lys Leu Tyr Leu Ile Gly Ser Ala
820 825 830
Glu Tyr Glu Lys Ser Lys Val Asn Lys Tyr Leu Lys Thr Ile Met Pro
835 840 845
Phe Asp Leu Ser Ile Tyr Thr Asn Asp Thr Ile Leu Ile Glu Met Phe
850 855 860
Asn Lys Tyr Asn Ser Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly
865 870 875 880
Ser Gly Gly Gly Gly Ser Ala Leu Val Gly Asn His Trp Ala Val Gly
885 890 895
His Leu Met
<210> 31
<211> 205
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 31
ggatccgtcg acaacaacaa taacaacaac aataacaaca acgacgatga cgataaacat 60
gtggatgcga tctttaccca gagctatcgg aaggttttgg cccaactgtc tgctcgtaaa 120
cttttacagg acattctgaa cagagcagaa gcggcagcca aagaagcagc cgctaaggcg 180
ctgcagagtc tagaataata agctt 205
<210> 32
<211> 2754
<212> DNA
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多核苷酸"
<400> 32
ggatccatga cgtggccagt taaggatttc aactactcag atcctgtaaa tgacaacgat 60
attctgtacc ttcgcattcc acaaaataaa ctgatcacca caccagtcaa agcattcatg 120
attactcaaa acatttgggt cattccagaa cgcttttcta gtgacacaaa tccgagttta 180
tctaaacctc cgcgtccgac gtccaaatat cagagctatt acgatccctc atatctcagt 240
acggacgaac aaaaagatac tttccttaaa ggtatcatta aactgtttaa gcgtattaat 300
gagcgcgata tcgggaaaaa gttgattaat tatcttgttg tgggttcccc gttcatgggc 360
gatagctcta cccccgaaga cacttttgat tttacccgtc atacgacaaa catcgcggta 420
gagaagtttg agaacggatc gtggaaagtc acaaacatca ttacacctag cgtcttaatt 480
tttggtccgc tgccaaacat cttagattat acagccagcc tgactttgca ggggcaacag 540
tcgaatccga gtttcgaagg ttttggtacc ctgagcattc tgaaagttgc cccggaattt 600
ctgctcactt tttcagatgt caccagcaac cagagctcag cagtattagg aaagtcaatt 660
ttttgcatgg acccggttat tgcactgatg cacgaactga cgcactctct gcatcaactg 720
tatgggatca acatccccag tgacaaacgt attcgtcccc aggtgtctga aggatttttc 780
tcacaggatg ggccgaacgt ccagttcgaa gagttgtata ctttcggagg cctggacgta 840
gagatcattc cccagattga gcgcagtcag ctgcgtgaga aggcattggg ccattataag 900
gatattgcaa aacgcctgaa taacattaac aaaacgattc catcttcgtg gatctcgaat 960
attgataaat ataagaaaat ttttagcgag aaatataatt ttgataaaga taatacaggt 1020
aactttgtgg ttaacattga caaattcaac tccctttaca gtgatttgac gaatgtaatg 1080
agcgaagttg tgtatagttc ccaatacaac gttaagaatc gtacccatta cttctctcgt 1140
cactacctgc cggttttcgc gaacatcctt gacgataata tttacactat tcgtgacggc 1200
tttaacttga ccaacaaggg cttcaatatt gaaaattcag gccagaacat tgaacgcaac 1260
ccggccttgc agaaactgtc gagtgaatcc gtggttgacc tgtttaccaa agtctgcgtc 1320
gacaacaaca ataacaacaa caataacaac aacgacgatg acgataaaca tgtggatgcg 1380
atctttaccc agagctatcg gaaggttttg gcccaactgt ctgctcgtaa acttttacag 1440
gacattctga acagagcaga agcggcagcc aaagaagcag ccgctaaggc gctgcagtgt 1500
attaaagtga aaaacaatcg gctgccttat gtagcagata aagatagcat tagtcaggag 1560
attttcgaaa ataaaattat cactgacgaa accaatgttc agaattattc agataaattt 1620
tcactggacg aaagcatctt agatggccaa gttccgatta acccggaaat tgttgatccg 1680
ttactgccga acgtgaatat ggaaccgtta aacctccctg gcgaagagat cgtattttat 1740
gatgacatta cgaaatatgt ggactacctt aattcttatt actatttgga aagccagaaa 1800
ctgtccaata acgtggaaaa cattactctg accacaagcg tggaagaggc tttaggctac 1860
tcaaataaga tttatacctt cctcccgtcg ctggcggaaa aagtaaataa aggtgtgcag 1920
gctggtctgt tcctcaactg ggcgaatgaa gttgtcgaag actttaccac gaatattatg 1980
aaaaaggata ccctggataa aatctccgac gtctcggtta ttatcccata tattggccct 2040
gcgttaaata tcggtaatag tgcgctgcgg gggaatttta accaggcctt tgctaccgcg 2100
ggcgtcgcgt tcctcctgga gggctttcct gaatttacta tcccggcgct cggtgttttt 2160
acattttact cttccatcca ggagcgtgag aaaattatca aaaccatcga aaactgcctg 2220
gagcagcggg tgaaacgctg gaaagattct tatcaatgga tggtgtcaaa ctggttatct 2280
cgcatcacga cccaattcaa ccatattaat taccagatgt atgatagtct gtcgtaccaa 2340
gctgacgcca ttaaagccaa aattgatctg gaatataaaa agtactctgg tagcgataag 2400
gagaacatca aaagccaggt ggagaacctt aagaatagtc tggatgtgaa aatctctgaa 2460
gctatgaata acattaacaa attcattcgt gaatgttcgg tgacgtacct gttcaagaat 2520
atgctgccaa aagttattga tgaactgaat aaatttgatc tgcgtaccaa aaccgaactt 2580
atcaacctca tcgactccca caacattatc cttgtgggcg aagtggatcg tctgaaggcc 2640
aaagtaaacg agagctttga aaatacgatg ccgtttaata ttttttcata taccaataac 2700
tccttgctga aagatatcat caatgaatat ttcaatctag aataatgaaa gctt 2754
<210> 33
<211> 909
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 33
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Asn Asn Asn Asn Asn Asn Asn Asn Asn Asn
435 440 445
Asp Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Gln Ser Tyr Arg
450 455 460
Lys Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu
465 470 475 480
Asn Arg Ala Glu Ala Ala Ala Lys Glu Ala Ala Ala Lys Ala Leu Gln
485 490 495
Cys Ile Lys Val Lys Asn Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp
500 505 510
Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr
515 520 525
Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu
530 535 540
Asp Gly Gln Val Pro Ile Asn Pro Glu Ile Val Asp Pro Leu Leu Pro
545 550 555 560
Asn Val Asn Met Glu Pro Leu Asn Leu Pro Gly Glu Glu Ile Val Phe
565 570 575
Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr
580 585 590
Leu Glu Ser Gln Lys Leu Ser Asn Asn Val Glu Asn Ile Thr Leu Thr
595 600 605
Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe
610 615 620
Leu Pro Ser Leu Ala Glu Lys Val Asn Lys Gly Val Gln Ala Gly Leu
625 630 635 640
Phe Leu Asn Trp Ala Asn Glu Val Val Glu Asp Phe Thr Thr Asn Ile
645 650 655
Met Lys Lys Asp Thr Leu Asp Lys Ile Ser Asp Val Ser Val Ile Ile
660 665 670
Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly
675 680 685
Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly Val Ala Phe Leu Leu Glu
690 695 700
Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr
705 710 715 720
Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys
725 730 735
Leu Glu Gln Arg Val Lys Arg Trp Lys Asp Ser Tyr Gln Trp Met Val
740 745 750
Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln Phe Asn His Ile Asn Tyr
755 760 765
Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys
770 775 780
Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile
785 790 795 800
Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp Val Lys Ile Ser
805 810 815
Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu Cys Ser Val Thr
820 825 830
Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp Glu Leu Asn Lys
835 840 845
Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile Asn Leu Ile Asp Ser His
850 855 860
Asn Ile Ile Leu Val Gly Glu Val Asp Arg Leu Lys Ala Lys Val Asn
865 870 875 880
Glu Ser Phe Glu Asn Thr Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn
885 890 895
Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe Asn
900 905
<210> 34
<211> 919
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 34
Glu Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly Val
1 5 10 15
Asp Ile Ala Tyr Ile Lys Ile Pro Asn Ala Gly Gln Met Gln Pro Val
20 25 30
Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg Asp
35 40 45
Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu Ala
50 55 60
Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr Asp
65 70 75 80
Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu Arg
85 90 95
Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val Arg
100 105 110
Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys Val
115 120 125
Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr Arg
130 135 140
Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile Ile
145 150 155 160
Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr Arg
165 170 175
Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe Thr
180 185 190
Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu Gly
195 200 205
Ala Gly Lys Phe Ala Thr Asp Pro Ala Val Thr Leu Ala His Glu Leu
210 215 220
Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn Arg
225 230 235 240
Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu Glu
245 250 255
Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys Phe
260 265 270
Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn Lys
275 280 285
Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val Gly
290 295 300
Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys Tyr
305 310 315 320
Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu Lys
325 330 335
Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp Asn
340 345 350
Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn Phe
355 360 365
Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr Thr
370 375 380
Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn Phe
385 390 395 400
Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu Lys
405 410 415
Asn Phe Thr Gly Leu Phe Glu Phe Tyr Lys Leu Leu Cys Val Asp Gly
420 425 430
Ile Ile Thr Ser Lys Thr Lys Ser Leu Ile Glu Gly Arg His Val Asp
435 440 445
Ala Ile Phe Thr Gln Ser Tyr Arg Lys Val Leu Ala Gln Leu Ser Ala
450 455 460
Arg Lys Leu Leu Gln Asp Ile Leu Asn Arg Gln Gln Gly Glu Arg Asn
465 470 475 480
Gln Glu Gln Gly Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
485 490 495
Ser Gly Gly Gly Gly Ser Ala Leu Val Leu Gln Cys Ile Lys Val Asn
500 505 510
Asn Trp Asp Leu Phe Phe Ser Pro Ser Glu Asp Asn Phe Thr Asn Asp
515 520 525
Leu Asn Lys Gly Glu Glu Ile Thr Ser Asp Thr Asn Ile Glu Ala Ala
530 535 540
Glu Glu Asn Ile Ser Leu Asp Leu Ile Gln Gln Tyr Tyr Leu Thr Phe
545 550 555 560
Asn Phe Asp Asn Glu Pro Glu Asn Ile Ser Ile Glu Asn Leu Ser Ser
565 570 575
Asp Ile Ile Gly Gln Leu Glu Leu Met Pro Asn Ile Glu Arg Phe Pro
580 585 590
Asn Gly Lys Lys Tyr Glu Leu Asp Lys Tyr Thr Met Phe His Tyr Leu
595 600 605
Arg Ala Gln Glu Phe Glu His Gly Lys Ser Arg Ile Ala Leu Thr Asn
610 615 620
Ser Val Asn Glu Ala Leu Leu Asn Pro Ser Arg Val Tyr Thr Phe Phe
625 630 635 640
Ser Ser Asp Tyr Val Lys Lys Val Asn Lys Ala Thr Glu Ala Ala Met
645 650 655
Phe Leu Gly Trp Val Glu Gln Leu Val Tyr Asp Phe Thr Asp Glu Thr
660 665 670
Ser Glu Val Ser Thr Thr Asp Lys Ile Ala Asp Ile Thr Ile Ile Ile
675 680 685
Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Met Leu Tyr Lys Asp
690 695 700
Asp Phe Val Gly Ala Leu Ile Phe Ser Gly Ala Val Ile Leu Leu Glu
705 710 715 720
Phe Ile Pro Glu Ile Ala Ile Pro Val Leu Gly Thr Phe Ala Leu Val
725 730 735
Ser Tyr Ile Ala Asn Lys Val Leu Thr Val Gln Thr Ile Asp Asn Ala
740 745 750
Leu Ser Lys Arg Asn Glu Lys Trp Asp Glu Val Tyr Lys Tyr Ile Val
755 760 765
Thr Asn Trp Leu Ala Lys Val Asn Thr Gln Ile Asp Leu Ile Arg Lys
770 775 780
Lys Met Lys Glu Ala Leu Glu Asn Gln Ala Glu Ala Thr Lys Ala Ile
785 790 795 800
Ile Asn Tyr Gln Tyr Asn Gln Tyr Thr Glu Glu Glu Lys Asn Asn Ile
805 810 815
Asn Phe Asn Ile Asp Asp Leu Ser Ser Lys Leu Asn Glu Ser Ile Asn
820 825 830
Lys Ala Met Ile Asn Ile Asn Lys Phe Leu Asn Gln Cys Ser Val Ser
835 840 845
Tyr Leu Met Asn Ser Met Ile Pro Tyr Gly Val Lys Arg Leu Glu Asp
850 855 860
Phe Asp Ala Ser Leu Lys Asp Ala Leu Leu Lys Tyr Ile Tyr Asp Asn
865 870 875 880
Arg Gly Thr Leu Ile Gly Gln Val Asp Arg Leu Lys Asp Lys Val Asn
885 890 895
Asn Thr Leu Ser Thr Asp Ile Pro Phe Gln Leu Ser Lys Tyr Val Asp
900 905 910
Asn Gln Arg Leu Leu Ser Thr
915
<210> 35
<211> 919
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 35
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg His Val Asp Ala Ile
435 440 445
Phe Thr Gln Ser Tyr Arg Lys Val Leu Ala Gln Leu Ser Ala Arg Lys
450 455 460
Leu Leu Gln Asp Ile Leu Asn Arg Gln Gln Gly Glu Arg Asn Gln Glu
465 470 475 480
Gln Gly Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
485 490 495
Gly Gly Gly Ser Ala Leu Val Leu Gln Cys Arg Glu Leu Leu Val Lys
500 505 510
Asn Thr Asp Leu Pro Phe Ile Gly Asp Ile Ser Asp Val Lys Thr Asp
515 520 525
Ile Phe Leu Arg Lys Asp Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr
530 535 540
Pro Asp Asn Val Ser Val Asp Gln Val Ile Leu Ser Lys Asn Thr Ser
545 550 555 560
Glu His Gly Gln Leu Asp Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser
565 570 575
Glu Ile Leu Pro Gly Glu Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln
580 585 590
Asn Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
595 600 605
Ser Asp Asn Val Glu Asp Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala
610 615 620
Leu Asp Asn Ser Ala Lys Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn
625 630 635 640
Lys Val Asn Ala Gly Val Gln Gly Gly Leu Phe Leu Met Trp Ala Asn
645 650 655
Asp Val Val Glu Asp Phe Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu
660 665 670
Asp Lys Ile Ser Asp Val Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala
675 680 685
Leu Asn Ile Ser Asn Ser Val Arg Arg Gly Asn Phe Thr Glu Ala Phe
690 695 700
Ala Val Thr Gly Val Thr Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr
705 710 715 720
Ile Pro Ala Leu Gly Ala Phe Val Ile Tyr Ser Lys Val Gln Glu Arg
725 730 735
Asn Glu Ile Ile Lys Thr Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys
740 745 750
Arg Trp Lys Asp Ser Tyr Glu Trp Met Met Gly Thr Trp Leu Ser Arg
755 760 765
Ile Ile Thr Gln Phe Asn Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu
770 775 780
Asn Tyr Gln Ala Gly Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
785 790 795 800
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
805 810 815
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
820 825 830
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
835 840 845
Leu Pro Lys Val Ile Asp Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys
850 855 860
Ala Lys Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
865 870 875 880
Glu Val Asp Lys Leu Lys Ala Lys Val Asn Asn Ser Phe Gln Asn Thr
885 890 895
Ile Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
900 905 910
Ile Ile Asn Glu Tyr Phe Asn
915
<210> 36
<211> 928
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 36
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Gln Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Asn
465 470 475 480
Arg Gln Gln Gly Glu Arg Asn Gln Glu Gln Gly Ala Ala Leu Ala Gly
485 490 495
Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu
500 505 510
Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu Pro Tyr Val Ala
515 520 525
Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys Ile Ile Thr
530 535 540
Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser Leu Asp Glu
545 550 555 560
Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu Ile Val Asp Pro
565 570 575
Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu Pro Gly Glu Glu
580 585 590
Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr Leu Asn Ser
595 600 605
Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn Val Glu Asn Ile
610 615 620
Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser Asn Lys Ile
625 630 635 640
Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn Lys Gly Val Gln
645 650 655
Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val Glu Asp Phe Thr
660 665 670
Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile Ser Asp Val Ser
675 680 685
Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Ser Ala
690 695 700
Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly Val Ala Phe
705 710 715 720
Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Val Phe
725 730 735
Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile Lys Thr Ile
740 745 750
Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys Asp Ser Tyr Gln
755 760 765
Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln Phe Asn His
770 775 780
Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala Asp Ala Ile
785 790 795 800
Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp Lys
805 810 815
Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp Val
820 825 830
Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu Cys
835 840 845
Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp Glu
850 855 860
Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile Asn Leu Ile
865 870 875 880
Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Arg Leu Lys Ala
885 890 895
Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe Asn Ile Phe Ser
900 905 910
Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe Asn
915 920 925
<210> 37
<211> 913
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 37
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Asn Asn Asn Asn Asn Asn Asn Asn Asn Asn
435 440 445
Asp Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Gln Ser Tyr Arg
450 455 460
Lys Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu
465 470 475 480
Asn Arg Gln Gln Gly Glu Arg Asn Gln Glu Gln Gly Ala Pro Ala Pro
485 490 495
Ala Pro Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu Pro Tyr Val
500 505 510
Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys Ile Ile
515 520 525
Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser Leu Asp
530 535 540
Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu Ile Val Asp
545 550 555 560
Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu Pro Gly Glu
565 570 575
Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr Leu Asn
580 585 590
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn Val Glu Asn
595 600 605
Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser Asn Lys
610 615 620
Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn Lys Gly Val
625 630 635 640
Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val Glu Asp Phe
645 650 655
Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
660 665 670
Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Ser
675 680 685
Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly Val Ala
690 695 700
Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Val
705 710 715 720
Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile Lys Thr
725 730 735
Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys Asp Ser Tyr
740 745 750
Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln Phe Asn
755 760 765
His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala Asp Ala
770 775 780
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
785 790 795 800
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
805 810 815
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
820 825 830
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
835 840 845
Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile Asn Leu
850 855 860
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Arg Leu Lys
865 870 875 880
Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe Asn Ile Phe
885 890 895
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
900 905 910
Asn
<210> 38
<211> 919
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 38
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Asn Asn Asn Asn Asn Asn Asn Asn Asn Asn
435 440 445
Asp Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Gln Ser Tyr Arg
450 455 460
Lys Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu
465 470 475 480
Asn Arg Gln Gln Gly Glu Arg Asn Gln Glu Gln Gly Ala Glu Ala Ala
485 490 495
Ala Lys Glu Ala Ala Ala Lys Ala Leu Gln Cys Ile Lys Val Lys Asn
500 505 510
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
515 520 525
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
530 535 540
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
545 550 555 560
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
565 570 575
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
580 585 590
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
595 600 605
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
610 615 620
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
625 630 635 640
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
645 650 655
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
660 665 670
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
675 680 685
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
690 695 700
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
705 710 715 720
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
725 730 735
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
740 745 750
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
755 760 765
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
770 775 780
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
785 790 795 800
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
805 810 815
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
820 825 830
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
835 840 845
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
850 855 860
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
865 870 875 880
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
885 890 895
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
900 905 910
Ile Ile Asn Glu Tyr Phe Asn
915
<210> 39
<211> 916
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 39
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Ser Ala Asn Ser Asn Pro Ala Met Ala Pro Arg Glu
450 455 460
Arg Lys Ala Gly Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr Ser Cys
465 470 475 480
Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
485 490 495
Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu
500 505 510
Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn
515 520 525
Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe
530 535 540
Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu
545 550 555 560
Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu
565 570 575
Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp
580 585 590
Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn
595 600 605
Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr
610 615 620
Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn
625 630 635 640
Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val
645 650 655
Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile
660 665 670
Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile
675 680 685
Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala
690 695 700
Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala
705 710 715 720
Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile
725 730 735
Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys
740 745 750
Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr
755 760 765
Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln
770 775 780
Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser
785 790 795 800
Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn
805 810 815
Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe
820 825 830
Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys
835 840 845
Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu
850 855 860
Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp
865 870 875 880
Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe
885 890 895
Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn
900 905 910
Glu Tyr Phe Asn
915
<210> 40
<211> 902
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 40
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Ala Gly Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr
450 455 460
Ser Cys Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
465 470 475 480
Gly Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn
485 490 495
Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe
500 505 510
Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp
515 520 525
Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn
530 535 540
Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu
545 550 555 560
Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr
565 570 575
Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser
580 585 590
Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu
595 600 605
Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys
610 615 620
Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu
625 630 635 640
Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp
645 650 655
Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu
660 665 670
Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala
675 680 685
Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile
690 695 700
Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu
705 710 715 720
Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg
725 730 735
Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile
740 745 750
Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser
755 760 765
Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys
770 775 780
Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu
785 790 795 800
Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn
805 810 815
Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu
820 825 830
Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr
835 840 845
Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu
850 855 860
Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met
865 870 875 880
Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile
885 890 895
Ile Asn Glu Tyr Phe Asn
900
<210> 41
<211> 710
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 41
Glu Ser Asn Gln Pro Glu Lys Asn Gly Thr Ala Thr Lys Pro Glu Asn
1 5 10 15
Ser Gly Asn Thr Thr Ser Glu Asn Gly Gln Thr Glu Pro Glu Lys Lys
20 25 30
Leu Glu Leu Arg Asn Val Ser Asp Ile Glu Leu Tyr Ser Gln Thr Asn
35 40 45
Gly Thr Tyr Arg Gln His Val Ser Leu Asp Gly Ile Pro Glu Asn Thr
50 55 60
Asp Thr Tyr Phe Val Lys Val Lys Ser Ser Ala Phe Lys Asp Val Tyr
65 70 75 80
Ile Pro Val Ala Ser Ile Thr Glu Glu Lys Arg Asn Gly Gln Ser Val
85 90 95
Tyr Lys Ile Thr Ala Lys Ala Glu Lys Leu Gln Gln Glu Leu Glu Asn
100 105 110
Lys Tyr Val Asp Asn Phe Thr Phe Tyr Leu Asp Lys Lys Ala Lys Glu
115 120 125
Glu Asn Thr Asn Phe Thr Ser Phe Ser Asn Leu Val Lys Ala Ile Asn
130 135 140
Gln Asn Pro Ser Gly Thr Tyr His Leu Ala Ala Ser Leu Asn Ala Asn
145 150 155 160
Glu Val Glu Leu Gly Pro Asp Glu Arg Ser Tyr Ile Lys Asp Thr Phe
165 170 175
Thr Gly Arg Leu Ile Gly Glu Lys Asp Gly Lys Asn Tyr Ala Ile Tyr
180 185 190
Asn Leu Lys Lys Pro Leu Phe Glu Asn Leu Ser Gly Ala Thr Val Glu
195 200 205
Lys Leu Ser Leu Lys Asn Val Ala Ile Ser Gly Lys Asn Asp Ile Gly
210 215 220
Ser Leu Ala Asn Glu Ala Thr Asn Gly Thr Lys Ile Lys Gln Val His
225 230 235 240
Val Asp Gly Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
245 250 255
Asp Asp Asp Lys Ala Gly Cys Lys Asn Phe Phe Trp Lys Thr Phe Thr
260 265 270
Ser Cys Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly
275 280 285
Gly Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Ile Lys Asn Glu
290 295 300
Asp Leu Thr Phe Ile Ala Glu Lys Asn Ser Phe Ser Glu Glu Pro Phe
305 310 315 320
Gln Asp Glu Ile Val Ser Tyr Asn Thr Lys Asn Lys Pro Leu Asn Phe
325 330 335
Asn Tyr Ser Leu Asp Lys Ile Ile Val Asp Tyr Asn Leu Gln Ser Lys
340 345 350
Ile Thr Leu Pro Asn Asp Arg Thr Thr Pro Val Thr Lys Gly Ile Pro
355 360 365
Tyr Ala Pro Glu Tyr Lys Ser Asn Ala Ala Ser Thr Ile Glu Ile His
370 375 380
Asn Ile Asp Asp Asn Thr Ile Tyr Gln Tyr Leu Tyr Ala Gln Lys Ser
385 390 395 400
Pro Thr Thr Leu Gln Arg Ile Thr Met Thr Asn Ser Val Asp Asp Ala
405 410 415
Leu Ile Asn Ser Thr Lys Ile Tyr Ser Tyr Phe Pro Ser Val Ile Ser
420 425 430
Lys Val Asn Gln Gly Ala Gln Gly Ile Leu Phe Leu Gln Trp Val Arg
435 440 445
Asp Ile Ile Asp Asp Phe Thr Asn Glu Ser Ser Gln Lys Thr Thr Ile
450 455 460
Asp Lys Ile Ser Asp Val Ser Thr Ile Val Pro Tyr Ile Gly Pro Ala
465 470 475 480
Leu Asn Ile Val Lys Gln Gly Tyr Glu Gly Asn Phe Ile Gly Ala Leu
485 490 495
Glu Thr Thr Gly Val Val Leu Leu Leu Glu Tyr Ile Pro Glu Ile Thr
500 505 510
Leu Pro Val Ile Ala Ala Leu Ser Ile Ala Glu Ser Ser Thr Gln Lys
515 520 525
Glu Lys Ile Ile Lys Thr Ile Asp Asn Phe Leu Glu Lys Arg Tyr Glu
530 535 540
Lys Trp Ile Glu Val Tyr Lys Leu Val Lys Ala Lys Trp Leu Gly Thr
545 550 555 560
Val Asn Thr Gln Phe Gln Lys Arg Ser Tyr Gln Met Tyr Arg Ser Leu
565 570 575
Glu Tyr Gln Val Asp Ala Ile Lys Lys Ile Ile Asp Tyr Glu Tyr Lys
580 585 590
Ile Tyr Ser Gly Pro Asp Lys Glu Gln Ile Ala Asp Glu Ile Asn Asn
595 600 605
Leu Lys Asn Lys Leu Glu Glu Lys Ala Asn Lys Ala Met Ile Asn Ile
610 615 620
Asn Ile Phe Met Arg Glu Ser Ser Arg Ser Phe Leu Val Asn Gln Met
625 630 635 640
Ile Asn Glu Ala Lys Lys Gln Leu Leu Glu Phe Asp Thr Gln Ser Lys
645 650 655
Asn Ile Leu Met Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile Gly Ile
660 665 670
Thr Glu Leu Lys Lys Leu Glu Ser Lys Ile Asn Lys Val Phe Ser Thr
675 680 685
Pro Ile Pro Phe Ser Tyr Ser Lys Asn Leu Asp Cys Trp Val Asp Asn
690 695 700
Glu Glu Asp Ile Asp Val
705 710
<210> 42
<211> 918
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 42
Glu Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly Val
1 5 10 15
Asp Ile Ala Tyr Ile Lys Ile Pro Asn Ala Gly Gln Met Gln Pro Val
20 25 30
Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg Asp
35 40 45
Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu Ala
50 55 60
Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr Asp
65 70 75 80
Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu Arg
85 90 95
Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val Arg
100 105 110
Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys Val
115 120 125
Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr Arg
130 135 140
Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile Ile
145 150 155 160
Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr Arg
165 170 175
Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe Thr
180 185 190
Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu Gly
195 200 205
Ala Gly Lys Phe Ala Thr Asp Pro Ala Val Thr Leu Ala His Glu Leu
210 215 220
Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn Arg
225 230 235 240
Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu Glu
245 250 255
Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys Phe
260 265 270
Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn Lys
275 280 285
Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val Gly
290 295 300
Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys Tyr
305 310 315 320
Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu Lys
325 330 335
Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp Asn
340 345 350
Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn Phe
355 360 365
Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr Thr
370 375 380
Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn Phe
385 390 395 400
Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu Lys
405 410 415
Asn Phe Thr Gly Leu Phe Glu Phe Tyr Lys Leu Leu Cys Val Asp Gly
420 425 430
Gly Gly Gly Ser Ala Asp Asp Asp Asp Lys Asn Asp Asp Pro Pro Ile
435 440 445
Ser Ile Asp Leu Thr Phe His Leu Leu Arg Asn Met Ile Glu Met Ala
450 455 460
Arg Ile Glu Asn Glu Arg Glu Gln Ala Gly Leu Asn Arg Lys Tyr Leu
465 470 475 480
Asp Glu Val Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
485 490 495
Gly Gly Gly Gly Ser Ala Leu Val Leu Gln Cys Ile Lys Val Asn Asn
500 505 510
Trp Asp Leu Phe Phe Ser Pro Ser Glu Asp Asn Phe Thr Asn Asp Leu
515 520 525
Asn Lys Gly Glu Glu Ile Thr Ser Asp Thr Asn Ile Glu Ala Ala Glu
530 535 540
Glu Asn Ile Ser Leu Asp Leu Ile Gln Gln Tyr Tyr Leu Thr Phe Asn
545 550 555 560
Phe Asp Asn Glu Pro Glu Asn Ile Ser Ile Glu Asn Leu Ser Ser Asp
565 570 575
Ile Ile Gly Gln Leu Glu Leu Met Pro Asn Ile Glu Arg Phe Pro Asn
580 585 590
Gly Lys Lys Tyr Glu Leu Asp Lys Tyr Thr Met Phe His Tyr Leu Arg
595 600 605
Ala Gln Glu Phe Glu His Gly Lys Ser Arg Ile Ala Leu Thr Asn Ser
610 615 620
Val Asn Glu Ala Leu Leu Asn Pro Ser Arg Val Tyr Thr Phe Phe Ser
625 630 635 640
Ser Asp Tyr Val Lys Lys Val Asn Lys Ala Thr Glu Ala Ala Met Phe
645 650 655
Leu Gly Trp Val Glu Gln Leu Val Tyr Asp Phe Thr Asp Glu Thr Ser
660 665 670
Glu Val Ser Thr Thr Asp Lys Ile Ala Asp Ile Thr Ile Ile Ile Pro
675 680 685
Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Met Leu Tyr Lys Asp Asp
690 695 700
Phe Val Gly Ala Leu Ile Phe Ser Gly Ala Val Ile Leu Leu Glu Phe
705 710 715 720
Ile Pro Glu Ile Ala Ile Pro Val Leu Gly Thr Phe Ala Leu Val Ser
725 730 735
Tyr Ile Ala Asn Lys Val Leu Thr Val Gln Thr Ile Asp Asn Ala Leu
740 745 750
Ser Lys Arg Asn Glu Lys Trp Asp Glu Val Tyr Lys Tyr Ile Val Thr
755 760 765
Asn Trp Leu Ala Lys Val Asn Thr Gln Ile Asp Leu Ile Arg Lys Lys
770 775 780
Met Lys Glu Ala Leu Glu Asn Gln Ala Glu Ala Thr Lys Ala Ile Ile
785 790 795 800
Asn Tyr Gln Tyr Asn Gln Tyr Thr Glu Glu Glu Lys Asn Asn Ile Asn
805 810 815
Phe Asn Ile Asp Asp Leu Ser Ser Lys Leu Asn Glu Ser Ile Asn Lys
820 825 830
Ala Met Ile Asn Ile Asn Lys Phe Leu Asn Gln Cys Ser Val Ser Tyr
835 840 845
Leu Met Asn Ser Met Ile Pro Tyr Gly Val Lys Arg Leu Glu Asp Phe
850 855 860
Asp Ala Ser Leu Lys Asp Ala Leu Leu Lys Tyr Ile Tyr Asp Asn Arg
865 870 875 880
Gly Thr Leu Ile Gly Gln Val Asp Arg Leu Lys Asp Lys Val Asn Asn
885 890 895
Thr Leu Ser Thr Asp Ile Pro Phe Gln Leu Ser Lys Tyr Val Asp Asn
900 905 910
Gln Arg Leu Leu Ser Thr
915
<210> 43
<211> 926
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 43
Pro Val Thr Ile Asn Asn Phe Asn Tyr Asn Asp Pro Ile Asp Asn Asn
1 5 10 15
Asn Ile Ile Met Met Glu Pro Pro Phe Ala Arg Gly Thr Gly Arg Tyr
20 25 30
Tyr Lys Ala Phe Lys Ile Thr Asp Arg Ile Trp Ile Ile Pro Glu Arg
35 40 45
Tyr Thr Phe Gly Tyr Lys Pro Glu Asp Phe Asn Lys Ser Ser Gly Ile
50 55 60
Phe Asn Arg Asp Val Cys Glu Tyr Tyr Asp Pro Asp Tyr Leu Asn Thr
65 70 75 80
Asn Asp Lys Lys Asn Ile Phe Leu Gln Thr Met Ile Lys Leu Phe Asn
85 90 95
Arg Ile Lys Ser Lys Pro Leu Gly Glu Lys Leu Leu Glu Met Ile Ile
100 105 110
Asn Gly Ile Pro Tyr Leu Gly Asp Arg Arg Val Pro Leu Glu Glu Phe
115 120 125
Asn Thr Asn Ile Ala Ser Val Thr Val Asn Lys Leu Ile Ser Asn Pro
130 135 140
Gly Glu Val Glu Arg Lys Lys Gly Ile Phe Ala Asn Leu Ile Ile Phe
145 150 155 160
Gly Pro Gly Pro Val Leu Asn Glu Asn Glu Thr Ile Asp Ile Gly Ile
165 170 175
Gln Asn His Phe Ala Ser Arg Glu Gly Phe Gly Gly Ile Met Gln Met
180 185 190
Lys Phe Cys Pro Glu Tyr Val Ser Val Phe Asn Asn Val Gln Glu Asn
195 200 205
Lys Gly Ala Ser Ile Phe Asn Arg Arg Gly Tyr Phe Ser Asp Pro Ala
210 215 220
Leu Ile Leu Met His Glu Leu Ile His Val Leu His Gly Leu Tyr Gly
225 230 235 240
Ile Lys Val Asp Asp Leu Pro Ile Val Pro Asn Glu Lys Lys Phe Phe
245 250 255
Met Gln Ser Thr Asp Ala Ile Gln Ala Glu Glu Leu Tyr Thr Phe Gly
260 265 270
Gly Gln Asp Pro Ser Ile Ile Thr Pro Ser Thr Asp Lys Ser Ile Tyr
275 280 285
Asp Lys Val Leu Gln Asn Phe Arg Gly Ile Val Asp Arg Leu Asn Lys
290 295 300
Val Leu Val Cys Ile Ser Asp Pro Asn Ile Asn Ile Asn Ile Tyr Lys
305 310 315 320
Asn Lys Phe Lys Asp Lys Tyr Lys Phe Val Glu Asp Ser Glu Gly Lys
325 330 335
Tyr Ser Ile Asp Val Glu Ser Phe Asp Lys Leu Tyr Lys Ser Leu Met
340 345 350
Phe Gly Phe Thr Glu Thr Asn Ile Ala Glu Asn Tyr Lys Ile Lys Thr
355 360 365
Arg Ala Ser Tyr Phe Ser Asp Ser Leu Pro Pro Val Lys Ile Lys Asn
370 375 380
Leu Leu Asp Asn Glu Ile Tyr Thr Ile Glu Glu Gly Phe Asn Ile Ser
385 390 395 400
Asp Lys Asp Met Glu Lys Glu Tyr Arg Gly Gln Asn Lys Ala Ile Asn
405 410 415
Lys Gln Ala Tyr Glu Glu Ile Ser Lys Glu His Leu Ala Val Tyr Lys
420 425 430
Ile Gln Met Cys Val Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
435 440 445
Ala Asp Asp Asp Asp Lys Val Val Ser His Phe Asn Asp Cys Pro Asp
450 455 460
Ser His Thr Gln Phe Cys Phe His Gly Thr Cys Arg Phe Leu Val Gln
465 470 475 480
Glu Asp Lys Pro Ala Cys Val Cys His Ser Gly Tyr Val Gly Ala Arg
485 490 495
Cys Glu His Ala Asp Leu Leu Ala Ala Leu Ala Lys Arg Leu Val Leu
500 505 510
Gln Cys Ile Asp Val Asp Asn Glu Asp Leu Phe Phe Ile Ala Asp Lys
515 520 525
Asn Ser Phe Ser Asp Asp Leu Ser Lys Asn Glu Arg Ile Glu Tyr Asn
530 535 540
Thr Gln Ser Asn Tyr Ile Glu Asn Asp Phe Pro Ile Asn Glu Leu Ile
545 550 555 560
Leu Asp Thr Asp Leu Ile Ser Lys Ile Glu Leu Pro Ser Glu Asn Thr
565 570 575
Glu Ser Leu Thr Asp Phe Asn Val Asp Val Pro Val Tyr Glu Lys Gln
580 585 590
Pro Ala Ile Lys Lys Ile Phe Thr Asp Glu Asn Thr Ile Phe Gln Tyr
595 600 605
Leu Tyr Ser Gln Thr Phe Pro Leu Asp Ile Arg Asp Ile Ser Leu Thr
610 615 620
Ser Ser Phe Asp Asp Ala Leu Leu Phe Ser Asn Lys Val Tyr Ser Phe
625 630 635 640
Phe Ser Met Asp Tyr Ile Lys Thr Ala Asn Lys Val Val Glu Ala Gly
645 650 655
Leu Phe Ala Gly Trp Val Lys Gln Ile Val Asn Asp Phe Val Ile Glu
660 665 670
Ala Asn Lys Ser Asn Thr Met Asp Ala Ile Ala Asp Ile Ser Leu Ile
675 680 685
Val Pro Tyr Ile Gly Leu Ala Leu Asn Val Gly Asn Glu Thr Ala Lys
690 695 700
Gly Asn Phe Glu Asn Ala Phe Glu Ile Ala Gly Ala Ser Ile Leu Leu
705 710 715 720
Glu Phe Ile Pro Glu Leu Leu Ile Pro Val Val Gly Ala Phe Leu Leu
725 730 735
Glu Ser Tyr Ile Asp Asn Lys Asn Lys Ile Ile Lys Thr Ile Asp Asn
740 745 750
Ala Leu Thr Lys Arg Asn Glu Lys Trp Ser Asp Met Tyr Gly Leu Ile
755 760 765
Val Ala Gln Trp Leu Ser Thr Val Asn Thr Gln Phe Tyr Thr Ile Lys
770 775 780
Glu Gly Met Tyr Lys Ala Leu Asn Tyr Gln Ala Gln Ala Leu Glu Glu
785 790 795 800
Ile Ile Lys Tyr Arg Tyr Asn Ile Tyr Ser Glu Lys Glu Lys Ser Asn
805 810 815
Ile Asn Ile Asp Phe Asn Asp Ile Asn Ser Lys Leu Asn Glu Gly Ile
820 825 830
Asn Gln Ala Ile Asp Asn Ile Asn Asn Phe Ile Asn Gly Cys Ser Val
835 840 845
Ser Tyr Leu Met Lys Lys Met Ile Pro Leu Ala Val Glu Lys Leu Leu
850 855 860
Asp Phe Asp Asn Thr Leu Lys Lys Asn Leu Leu Asn Tyr Ile Asp Glu
865 870 875 880
Asn Lys Leu Tyr Leu Ile Gly Ser Ala Glu Tyr Glu Lys Ser Lys Val
885 890 895
Asn Lys Tyr Leu Lys Thr Ile Met Pro Phe Asp Leu Ser Ile Tyr Thr
900 905 910
Asn Asp Thr Ile Leu Ile Glu Met Phe Asn Lys Tyr Asn Ser
915 920 925
<210> 44
<211> 940
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 44
Pro Val Thr Ile Asn Asn Phe Asn Tyr Asn Asp Pro Ile Asp Asn Asn
1 5 10 15
Asn Ile Ile Met Met Glu Pro Pro Phe Ala Arg Gly Thr Gly Arg Tyr
20 25 30
Tyr Lys Ala Phe Lys Ile Thr Asp Arg Ile Trp Ile Ile Pro Glu Arg
35 40 45
Tyr Thr Phe Gly Tyr Lys Pro Glu Asp Phe Asn Lys Ser Ser Gly Ile
50 55 60
Phe Asn Arg Asp Val Cys Glu Tyr Tyr Asp Pro Asp Tyr Leu Asn Thr
65 70 75 80
Asn Asp Lys Lys Asn Ile Phe Leu Gln Thr Met Ile Lys Leu Phe Asn
85 90 95
Arg Ile Lys Ser Lys Pro Leu Gly Glu Lys Leu Leu Glu Met Ile Ile
100 105 110
Asn Gly Ile Pro Tyr Leu Gly Asp Arg Arg Val Pro Leu Glu Glu Phe
115 120 125
Asn Thr Asn Ile Ala Ser Val Thr Val Asn Lys Leu Ile Ser Asn Pro
130 135 140
Gly Glu Val Glu Arg Lys Lys Gly Ile Phe Ala Asn Leu Ile Ile Phe
145 150 155 160
Gly Pro Gly Pro Val Leu Asn Glu Asn Glu Thr Ile Asp Ile Gly Ile
165 170 175
Gln Asn His Phe Ala Ser Arg Glu Gly Phe Gly Gly Ile Met Gln Met
180 185 190
Lys Phe Cys Pro Glu Tyr Val Ser Val Phe Asn Asn Val Gln Glu Asn
195 200 205
Lys Gly Ala Ser Ile Phe Asn Arg Arg Gly Tyr Phe Ser Asp Pro Ala
210 215 220
Leu Ile Leu Met His Glu Leu Ile His Val Leu His Gly Leu Tyr Gly
225 230 235 240
Ile Lys Val Asp Asp Leu Pro Ile Val Pro Asn Glu Lys Lys Phe Phe
245 250 255
Met Gln Ser Thr Asp Ala Ile Gln Ala Glu Glu Leu Tyr Thr Phe Gly
260 265 270
Gly Gln Asp Pro Ser Ile Ile Thr Pro Ser Thr Asp Lys Ser Ile Tyr
275 280 285
Asp Lys Val Leu Gln Asn Phe Arg Gly Ile Val Asp Arg Leu Asn Lys
290 295 300
Val Leu Val Cys Ile Ser Asp Pro Asn Ile Asn Ile Asn Ile Tyr Lys
305 310 315 320
Asn Lys Phe Lys Asp Lys Tyr Lys Phe Val Glu Asp Ser Glu Gly Lys
325 330 335
Tyr Ser Ile Asp Val Glu Ser Phe Asp Lys Leu Tyr Lys Ser Leu Met
340 345 350
Phe Gly Phe Thr Glu Thr Asn Ile Ala Glu Asn Tyr Lys Ile Lys Thr
355 360 365
Arg Ala Ser Tyr Phe Ser Asp Ser Leu Pro Pro Val Lys Ile Lys Asn
370 375 380
Leu Leu Asp Asn Glu Ile Tyr Thr Ile Glu Glu Gly Phe Asn Ile Ser
385 390 395 400
Asp Lys Asp Met Glu Lys Glu Tyr Arg Gly Gln Asn Lys Ala Ile Asn
405 410 415
Lys Gln Ala Tyr Glu Glu Ile Ser Lys Glu His Leu Ala Val Tyr Lys
420 425 430
Ile Gln Met Cys Val Asp Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser
435 440 445
Ala Asp Asp Asp Asp Lys Val Val Ser His Phe Asn Asp Cys Pro Asp
450 455 460
Ser His Thr Gln Phe Cys Phe His Gly Thr Cys Arg Phe Leu Val Gln
465 470 475 480
Glu Asp Lys Pro Ala Cys Val Cys His Ser Gly Tyr Val Gly Ala Arg
485 490 495
Cys Glu His Ala Asp Leu Leu Ala Ala Leu Ala Gly Gly Gly Gly Ser
500 505 510
Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Leu Gln Cys
515 520 525
Ile Asp Val Asp Asn Glu Asp Leu Phe Phe Ile Ala Asp Lys Asn Ser
530 535 540
Phe Ser Asp Asp Leu Ser Lys Asn Glu Arg Ile Glu Tyr Asn Thr Gln
545 550 555 560
Ser Asn Tyr Ile Glu Asn Asp Phe Pro Ile Asn Glu Leu Ile Leu Asp
565 570 575
Thr Asp Leu Ile Ser Lys Ile Glu Leu Pro Ser Glu Asn Thr Glu Ser
580 585 590
Leu Thr Asp Phe Asn Val Asp Val Pro Val Tyr Glu Lys Gln Pro Ala
595 600 605
Ile Lys Lys Ile Phe Thr Asp Glu Asn Thr Ile Phe Gln Tyr Leu Tyr
610 615 620
Ser Gln Thr Phe Pro Leu Asp Ile Arg Asp Ile Ser Leu Thr Ser Ser
625 630 635 640
Phe Asp Asp Ala Leu Leu Phe Ser Asn Lys Val Tyr Ser Phe Phe Ser
645 650 655
Met Asp Tyr Ile Lys Thr Ala Asn Lys Val Val Glu Ala Gly Leu Phe
660 665 670
Ala Gly Trp Val Lys Gln Ile Val Asn Asp Phe Val Ile Glu Ala Asn
675 680 685
Lys Ser Asn Thr Met Asp Ala Ile Ala Asp Ile Ser Leu Ile Val Pro
690 695 700
Tyr Ile Gly Leu Ala Leu Asn Val Gly Asn Glu Thr Ala Lys Gly Asn
705 710 715 720
Phe Glu Asn Ala Phe Glu Ile Ala Gly Ala Ser Ile Leu Leu Glu Phe
725 730 735
Ile Pro Glu Leu Leu Ile Pro Val Val Gly Ala Phe Leu Leu Glu Ser
740 745 750
Tyr Ile Asp Asn Lys Asn Lys Ile Ile Lys Thr Ile Asp Asn Ala Leu
755 760 765
Thr Lys Arg Asn Glu Lys Trp Ser Asp Met Tyr Gly Leu Ile Val Ala
770 775 780
Gln Trp Leu Ser Thr Val Asn Thr Gln Phe Tyr Thr Ile Lys Glu Gly
785 790 795 800
Met Tyr Lys Ala Leu Asn Tyr Gln Ala Gln Ala Leu Glu Glu Ile Ile
805 810 815
Lys Tyr Arg Tyr Asn Ile Tyr Ser Glu Lys Glu Lys Ser Asn Ile Asn
820 825 830
Ile Asp Phe Asn Asp Ile Asn Ser Lys Leu Asn Glu Gly Ile Asn Gln
835 840 845
Ala Ile Asp Asn Ile Asn Asn Phe Ile Asn Gly Cys Ser Val Ser Tyr
850 855 860
Leu Met Lys Lys Met Ile Pro Leu Ala Val Glu Lys Leu Leu Asp Phe
865 870 875 880
Asp Asn Thr Leu Lys Lys Asn Leu Leu Asn Tyr Ile Asp Glu Asn Lys
885 890 895
Leu Tyr Leu Ile Gly Ser Ala Glu Tyr Glu Lys Ser Lys Val Asn Lys
900 905 910
Tyr Leu Lys Thr Ile Met Pro Phe Asp Leu Ser Ile Tyr Thr Asn Asp
915 920 925
Thr Ile Leu Ile Glu Met Phe Asn Lys Tyr Asn Ser
930 935 940
<210> 45
<211> 864
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 45
Glu Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly Val
1 5 10 15
Asp Ile Ala Tyr Ile Lys Ile Pro Asn Ala Gly Gln Met Gln Pro Val
20 25 30
Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg Asp
35 40 45
Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu Ala
50 55 60
Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr Asp
65 70 75 80
Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu Arg
85 90 95
Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val Arg
100 105 110
Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys Val
115 120 125
Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr Arg
130 135 140
Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile Ile
145 150 155 160
Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr Arg
165 170 175
Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe Thr
180 185 190
Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu Gly
195 200 205
Ala Gly Lys Phe Ala Thr Asp Pro Ala Val Thr Leu Ala His Glu Leu
210 215 220
Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn Arg
225 230 235 240
Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu Glu
245 250 255
Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys Phe
260 265 270
Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn Lys
275 280 285
Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val Gly
290 295 300
Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys Tyr
305 310 315 320
Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu Lys
325 330 335
Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp Asn
340 345 350
Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn Phe
355 360 365
Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr Thr
370 375 380
Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn Phe
385 390 395 400
Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu Lys
405 410 415
Asn Phe Thr Gly Leu Phe Glu Phe Tyr Lys Leu Leu Cys Val Asp Gly
420 425 430
Ile Ile Thr Ser Lys Thr Lys Ser Asp Asp Asp Asp Lys Asn Lys Ala
435 440 445
Leu Asn Leu Gln Cys Ile Lys Val Asn Asn Trp Asp Leu Phe Phe Ser
450 455 460
Pro Ser Glu Asp Asn Phe Thr Asn Asp Leu Asn Lys Gly Glu Glu Ile
465 470 475 480
Thr Ser Asp Thr Asn Ile Glu Ala Ala Glu Glu Asn Ile Ser Leu Asp
485 490 495
Leu Ile Gln Gln Tyr Tyr Leu Thr Phe Asn Phe Asp Asn Glu Pro Glu
500 505 510
Asn Ile Ser Ile Glu Asn Leu Ser Ser Asp Ile Ile Gly Gln Leu Glu
515 520 525
Leu Met Pro Asn Ile Glu Arg Phe Pro Asn Gly Lys Lys Tyr Glu Leu
530 535 540
Asp Lys Tyr Thr Met Phe His Tyr Leu Arg Ala Gln Glu Phe Glu His
545 550 555 560
Gly Lys Ser Arg Ile Ala Leu Thr Asn Ser Val Asn Glu Ala Leu Leu
565 570 575
Asn Pro Ser Arg Val Tyr Thr Phe Phe Ser Ser Asp Tyr Val Lys Lys
580 585 590
Val Asn Lys Ala Thr Glu Ala Ala Met Phe Leu Gly Trp Val Glu Gln
595 600 605
Leu Val Tyr Asp Phe Thr Asp Glu Thr Ser Glu Val Ser Thr Thr Asp
610 615 620
Lys Ile Ala Asp Ile Thr Ile Ile Ile Pro Tyr Ile Gly Pro Ala Leu
625 630 635 640
Asn Ile Gly Asn Met Leu Tyr Lys Asp Asp Phe Val Gly Ala Leu Ile
645 650 655
Phe Ser Gly Ala Val Ile Leu Leu Glu Phe Ile Pro Glu Ile Ala Ile
660 665 670
Pro Val Leu Gly Thr Phe Ala Leu Val Ser Tyr Ile Ala Asn Lys Val
675 680 685
Leu Thr Val Gln Thr Ile Asp Asn Ala Leu Ser Lys Arg Asn Glu Lys
690 695 700
Trp Asp Glu Val Tyr Lys Tyr Ile Val Thr Asn Trp Leu Ala Lys Val
705 710 715 720
Asn Thr Gln Ile Asp Leu Ile Arg Lys Lys Met Lys Glu Ala Leu Glu
725 730 735
Asn Gln Ala Glu Ala Thr Lys Ala Ile Ile Asn Tyr Gln Tyr Asn Gln
740 745 750
Tyr Thr Glu Glu Glu Lys Asn Asn Ile Asn Phe Asn Ile Asp Asp Leu
755 760 765
Ser Ser Lys Leu Asn Glu Ser Ile Asn Lys Ala Met Ile Asn Ile Asn
770 775 780
Lys Phe Leu Asn Gln Cys Ser Val Ser Tyr Leu Met Asn Ser Met Ile
785 790 795 800
Pro Tyr Gly Val Lys Arg Leu Glu Asp Phe Asp Ala Ser Leu Lys Asp
805 810 815
Ala Leu Leu Lys Tyr Ile Tyr Asp Asn Arg Gly Thr Leu Ile Gly Gln
820 825 830
Val Asp Arg Leu Lys Asp Lys Val Asn Asn Thr Leu Ser Thr Asp Ile
835 840 845
Pro Phe Gln Leu Ser Lys Tyr Val Asp Asn Gln Arg Leu Leu Ser Thr
850 855 860
<210> 46
<211> 869
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 46
Pro Val Thr Ile Asn Asn Phe Asn Tyr Asn Asp Pro Ile Asp Asn Asn
1 5 10 15
Asn Ile Ile Met Met Glu Pro Pro Phe Ala Arg Gly Thr Gly Arg Tyr
20 25 30
Tyr Lys Ala Phe Lys Ile Thr Asp Arg Ile Trp Ile Ile Pro Glu Arg
35 40 45
Tyr Thr Phe Gly Tyr Lys Pro Glu Asp Phe Asn Lys Ser Ser Gly Ile
50 55 60
Phe Asn Arg Asp Val Cys Glu Tyr Tyr Asp Pro Asp Tyr Leu Asn Thr
65 70 75 80
Asn Asp Lys Lys Asn Ile Phe Leu Gln Thr Met Ile Lys Leu Phe Asn
85 90 95
Arg Ile Lys Ser Lys Pro Leu Gly Glu Lys Leu Leu Glu Met Ile Ile
100 105 110
Asn Gly Ile Pro Tyr Leu Gly Asp Arg Arg Val Pro Leu Glu Glu Phe
115 120 125
Asn Thr Asn Ile Ala Ser Val Thr Val Asn Lys Leu Ile Ser Asn Pro
130 135 140
Gly Glu Val Glu Arg Lys Lys Gly Ile Phe Ala Asn Leu Ile Ile Phe
145 150 155 160
Gly Pro Gly Pro Val Leu Asn Glu Asn Glu Thr Ile Asp Ile Gly Ile
165 170 175
Gln Asn His Phe Ala Ser Arg Glu Gly Phe Gly Gly Ile Met Gln Met
180 185 190
Lys Phe Cys Pro Glu Tyr Val Ser Val Phe Asn Asn Val Gln Glu Asn
195 200 205
Lys Gly Ala Ser Ile Phe Asn Arg Arg Gly Tyr Phe Ser Asp Pro Ala
210 215 220
Leu Ile Leu Met His Glu Leu Ile His Val Leu His Gly Leu Tyr Gly
225 230 235 240
Ile Lys Val Asp Asp Leu Pro Ile Val Pro Asn Glu Lys Lys Phe Phe
245 250 255
Met Gln Ser Thr Asp Ala Ile Gln Ala Glu Glu Leu Tyr Thr Phe Gly
260 265 270
Gly Gln Asp Pro Ser Ile Ile Thr Pro Ser Thr Asp Lys Ser Ile Tyr
275 280 285
Asp Lys Val Leu Gln Asn Phe Arg Gly Ile Val Asp Arg Leu Asn Lys
290 295 300
Val Leu Val Cys Ile Ser Asp Pro Asn Ile Asn Ile Asn Ile Tyr Lys
305 310 315 320
Asn Lys Phe Lys Asp Lys Tyr Lys Phe Val Glu Asp Ser Glu Gly Lys
325 330 335
Tyr Ser Ile Asp Val Glu Ser Phe Asp Lys Leu Tyr Lys Ser Leu Met
340 345 350
Phe Gly Phe Thr Glu Thr Asn Ile Ala Glu Asn Tyr Lys Ile Lys Thr
355 360 365
Arg Ala Ser Tyr Phe Ser Asp Ser Leu Pro Pro Val Lys Ile Lys Asn
370 375 380
Leu Leu Asp Asn Glu Ile Tyr Thr Ile Glu Glu Gly Phe Asn Ile Ser
385 390 395 400
Asp Lys Asp Met Glu Lys Glu Tyr Arg Gly Gln Asn Lys Ala Ile Asn
405 410 415
Lys Gln Ala Tyr Glu Glu Ile Ser Lys Glu His Leu Ala Val Tyr Lys
420 425 430
Ile Gln Met Cys Val Asp Glu Glu Lys Leu Tyr Asp Asp Asp Asp Lys
435 440 445
Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Asp Val Asp Asn Glu Asp
450 455 460
Leu Phe Phe Ile Ala Asp Lys Asn Ser Phe Ser Asp Asp Leu Ser Lys
465 470 475 480
Asn Glu Arg Ile Glu Tyr Asn Thr Gln Ser Asn Tyr Ile Glu Asn Asp
485 490 495
Phe Pro Ile Asn Glu Leu Ile Leu Asp Thr Asp Leu Ile Ser Lys Ile
500 505 510
Glu Leu Pro Ser Glu Asn Thr Glu Ser Leu Thr Asp Phe Asn Val Asp
515 520 525
Val Pro Val Tyr Glu Lys Gln Pro Ala Ile Lys Lys Ile Phe Thr Asp
530 535 540
Glu Asn Thr Ile Phe Gln Tyr Leu Tyr Ser Gln Thr Phe Pro Leu Asp
545 550 555 560
Ile Arg Asp Ile Ser Leu Thr Ser Ser Phe Asp Asp Ala Leu Leu Phe
565 570 575
Ser Asn Lys Val Tyr Ser Phe Phe Ser Met Asp Tyr Ile Lys Thr Ala
580 585 590
Asn Lys Val Val Glu Ala Gly Leu Phe Ala Gly Trp Val Lys Gln Ile
595 600 605
Val Asn Asp Phe Val Ile Glu Ala Asn Lys Ser Asn Thr Met Asp Ala
610 615 620
Ile Ala Asp Ile Ser Leu Ile Val Pro Tyr Ile Gly Leu Ala Leu Asn
625 630 635 640
Val Gly Asn Glu Thr Ala Lys Gly Asn Phe Glu Asn Ala Phe Glu Ile
645 650 655
Ala Gly Ala Ser Ile Leu Leu Glu Phe Ile Pro Glu Leu Leu Ile Pro
660 665 670
Val Val Gly Ala Phe Leu Leu Glu Ser Tyr Ile Asp Asn Lys Asn Lys
675 680 685
Ile Ile Lys Thr Ile Asp Asn Ala Leu Thr Lys Arg Asn Glu Lys Trp
690 695 700
Ser Asp Met Tyr Gly Leu Ile Val Ala Gln Trp Leu Ser Thr Val Asn
705 710 715 720
Thr Gln Phe Tyr Thr Ile Lys Glu Gly Met Tyr Lys Ala Leu Asn Tyr
725 730 735
Gln Ala Gln Ala Leu Glu Glu Ile Ile Lys Tyr Arg Tyr Asn Ile Tyr
740 745 750
Ser Glu Lys Glu Lys Ser Asn Ile Asn Ile Asp Phe Asn Asp Ile Asn
755 760 765
Ser Lys Leu Asn Glu Gly Ile Asn Gln Ala Ile Asp Asn Ile Asn Asn
770 775 780
Phe Ile Asn Gly Cys Ser Val Ser Tyr Leu Met Lys Lys Met Ile Pro
785 790 795 800
Leu Ala Val Glu Lys Leu Leu Asp Phe Asp Asn Thr Leu Lys Lys Asn
805 810 815
Leu Leu Asn Tyr Ile Asp Glu Asn Lys Leu Tyr Leu Ile Gly Ser Ala
820 825 830
Glu Tyr Glu Lys Ser Lys Val Asn Lys Tyr Leu Lys Thr Ile Met Pro
835 840 845
Phe Asp Leu Ser Ile Tyr Thr Asn Asp Thr Ile Leu Ile Glu Met Phe
850 855 860
Asn Lys Tyr Asn Ser
865
<210> 47
<211> 865
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 47
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Ala Ile Asp Gly Arg Ser Leu Tyr Asn Lys
435 440 445
Thr Leu Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe
450 455 460
Ile Gly Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp
465 470 475 480
Ile Asn Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val
485 490 495
Asp Gln Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp
500 505 510
Leu Leu Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu
515 520 525
Asn Gln Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn
530 535 540
Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp
545 550 555 560
Phe Thr Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys
565 570 575
Val Tyr Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val
580 585 590
Gln Gly Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe
595 600 605
Thr Thr Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val
610 615 620
Ser Ala Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser
625 630 635 640
Val Arg Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr
645 650 655
Ile Leu Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala
660 665 670
Phe Val Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr
675 680 685
Ile Asp Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr
690 695 700
Glu Trp Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn
705 710 715 720
Asn Ile Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala
725 730 735
Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp
740 745 750
Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp
755 760 765
Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu
770 775 780
Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp
785 790 795 800
Glu Leu Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu
805 810 815
Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys
820 825 830
Ala Lys Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe
835 840 845
Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe
850 855 860
Asn
865
<210> 48
<211> 871
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 48
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn
865 870
<210> 49
<211> 680
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 49
Glu Ser Asn Gln Pro Glu Lys Asn Gly Thr Ala Thr Lys Pro Glu Asn
1 5 10 15
Ser Gly Asn Thr Thr Ser Glu Asn Gly Gln Thr Glu Pro Glu Lys Lys
20 25 30
Leu Glu Leu Arg Asn Val Ser Asp Ile Glu Leu Tyr Ser Gln Thr Asn
35 40 45
Gly Thr Tyr Arg Gln His Val Ser Leu Asp Gly Ile Pro Glu Asn Thr
50 55 60
Asp Thr Tyr Phe Val Lys Val Lys Ser Ser Ala Phe Lys Asp Val Tyr
65 70 75 80
Ile Pro Val Ala Ser Ile Thr Glu Glu Lys Arg Asn Gly Gln Ser Val
85 90 95
Tyr Lys Ile Thr Ala Lys Ala Glu Lys Leu Gln Gln Glu Leu Glu Asn
100 105 110
Lys Tyr Val Asp Asn Phe Thr Phe Tyr Leu Asp Lys Lys Ala Lys Glu
115 120 125
Glu Asn Thr Asn Phe Thr Ser Phe Ser Asn Leu Val Lys Ala Ile Asn
130 135 140
Gln Asn Pro Ser Gly Thr Tyr His Leu Ala Ala Ser Leu Asn Ala Asn
145 150 155 160
Glu Val Glu Leu Gly Pro Asp Glu Arg Ser Tyr Ile Lys Asp Thr Phe
165 170 175
Thr Gly Arg Leu Ile Gly Glu Lys Asp Gly Lys Asn Tyr Ala Ile Tyr
180 185 190
Asn Leu Lys Lys Pro Leu Phe Glu Asn Leu Ser Gly Ala Thr Val Glu
195 200 205
Lys Leu Ser Leu Lys Asn Val Ala Ile Ser Gly Lys Asn Asp Ile Gly
210 215 220
Ser Leu Ala Asn Glu Ala Thr Asn Gly Thr Lys Ile Lys Gln Val His
225 230 235 240
Val Asp Gly Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
245 250 255
Asp Asp Asp Lys Asn Lys Ala Leu Asn Leu Gln Cys Ile Lys Ile Lys
260 265 270
Asn Glu Asp Leu Thr Phe Ile Ala Glu Lys Asn Ser Phe Ser Glu Glu
275 280 285
Pro Phe Gln Asp Glu Ile Val Ser Tyr Asn Thr Lys Asn Lys Pro Leu
290 295 300
Asn Phe Asn Tyr Ser Leu Asp Lys Ile Ile Val Asp Tyr Asn Leu Gln
305 310 315 320
Ser Lys Ile Thr Leu Pro Asn Asp Arg Thr Thr Pro Val Thr Lys Gly
325 330 335
Ile Pro Tyr Ala Pro Glu Tyr Lys Ser Asn Ala Ala Ser Thr Ile Glu
340 345 350
Ile His Asn Ile Asp Asp Asn Thr Ile Tyr Gln Tyr Leu Tyr Ala Gln
355 360 365
Lys Ser Pro Thr Thr Leu Gln Arg Ile Thr Met Thr Asn Ser Val Asp
370 375 380
Asp Ala Leu Ile Asn Ser Thr Lys Ile Tyr Ser Tyr Phe Pro Ser Val
385 390 395 400
Ile Ser Lys Val Asn Gln Gly Ala Gln Gly Ile Leu Phe Leu Gln Trp
405 410 415
Val Arg Asp Ile Ile Asp Asp Phe Thr Asn Glu Ser Ser Gln Lys Thr
420 425 430
Thr Ile Asp Lys Ile Ser Asp Val Ser Thr Ile Val Pro Tyr Ile Gly
435 440 445
Pro Ala Leu Asn Ile Val Lys Gln Gly Tyr Glu Gly Asn Phe Ile Gly
450 455 460
Ala Leu Glu Thr Thr Gly Val Val Leu Leu Leu Glu Tyr Ile Pro Glu
465 470 475 480
Ile Thr Leu Pro Val Ile Ala Ala Leu Ser Ile Ala Glu Ser Ser Thr
485 490 495
Gln Lys Glu Lys Ile Ile Lys Thr Ile Asp Asn Phe Leu Glu Lys Arg
500 505 510
Tyr Glu Lys Trp Ile Glu Val Tyr Lys Leu Val Lys Ala Lys Trp Leu
515 520 525
Gly Thr Val Asn Thr Gln Phe Gln Lys Arg Ser Tyr Gln Met Tyr Arg
530 535 540
Ser Leu Glu Tyr Gln Val Asp Ala Ile Lys Lys Ile Ile Asp Tyr Glu
545 550 555 560
Tyr Lys Ile Tyr Ser Gly Pro Asp Lys Glu Gln Ile Ala Asp Glu Ile
565 570 575
Asn Asn Leu Lys Asn Lys Leu Glu Glu Lys Ala Asn Lys Ala Met Ile
580 585 590
Asn Ile Asn Ile Phe Met Arg Glu Ser Ser Arg Ser Phe Leu Val Asn
595 600 605
Gln Met Ile Asn Glu Ala Lys Lys Gln Leu Leu Glu Phe Asp Thr Gln
610 615 620
Ser Lys Asn Ile Leu Met Gln Tyr Ile Lys Ala Asn Ser Lys Phe Ile
625 630 635 640
Gly Ile Thr Glu Leu Lys Lys Leu Glu Ser Lys Ile Asn Lys Val Phe
645 650 655
Ser Thr Pro Ile Pro Phe Ser Tyr Ser Lys Asn Leu Asp Cys Trp Val
660 665 670
Asp Asn Glu Glu Asp Ile Asp Val
675 680
<210> 50
<211> 9
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
肽"
<220>
<221> MOD_RES
<222> (2)..(2)
<223> D-Phe
<220>
<221> MOD_RES
<222> (5)..(5)
<223> D-Trp
<220>
<221> misc_feature
<222> (9)..(9)
<223> /注释="C-端-醇"
<400> 50
Cys Phe Cys Phe Trp Lys Thr Cys Thr
1 5
<210> 51
<211> 30
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<220>
<221> MOD_RES
<222> (27)..(27)
<223> 正亮氨酸
<400> 51
His Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys Val Leu Gly Gln
1 5 10 15
Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Ser Arg Cys
20 25 30
<210> 52
<211> 30
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<220>
<221> MOD_RES
<222> (1)..(1)
<223> PhAc-Tyr
<220>
<221> MOD_RES
<222> (2)..(2)
<223> D-Arg
<220>
<221> MOD_RES
<222> (6)..(6)
<223> Phe(4-Cl)
<220>
<221> MOD_RES
<222> (9)..(9)
<223> 高精氨酸
<220>
<221> MOD_RES
<222> (10)..(10)
<223> Tyr(Me)
<220>
<221> MOD_RES
<222> (15)..(15)
<223> α-氨基丁酸
<220>
<221> MOD_RES
<222> (27)..(27)
<223> 正亮氨酸
<220>
<221> MOD_RES
<222> (28)..(28)
<223> D-Arg
<220>
<221> MOD_RES
<222> (29)..(29)
<223> 高精氨酸
<400> 52
Tyr Arg Asp Ala Ile Phe Thr Ala Arg Tyr His Lys Val Leu Xaa Gln
1 5 10 15
Leu Ser Ala His Lys Leu Leu Gln Asp Ile Leu Arg Arg Cys
20 25 30
<210> 53
<211> 893
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 53
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Asp Phe Asp Met Leu Arg Cys Met Leu Gly Arg Val
450 455 460
Tyr Arg Pro Cys Trp Gln Val Ala Leu Ala Lys Arg Leu Val Leu Gln
465 470 475 480
Cys Ile Lys Val Lys Asn Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp
485 490 495
Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr
500 505 510
Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu
515 520 525
Asp Gly Gln Val Pro Ile Asn Pro Glu Ile Val Asp Pro Leu Leu Pro
530 535 540
Asn Val Asn Met Glu Pro Leu Asn Leu Pro Gly Glu Glu Ile Val Phe
545 550 555 560
Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr
565 570 575
Leu Glu Ser Gln Lys Leu Ser Asn Asn Val Glu Asn Ile Thr Leu Thr
580 585 590
Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe
595 600 605
Leu Pro Ser Leu Ala Glu Lys Val Asn Lys Gly Val Gln Ala Gly Leu
610 615 620
Phe Leu Asn Trp Ala Asn Glu Val Val Glu Asp Phe Thr Thr Asn Ile
625 630 635 640
Met Lys Lys Asp Thr Leu Asp Lys Ile Ser Asp Val Ser Val Ile Ile
645 650 655
Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly
660 665 670
Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly Val Ala Phe Leu Leu Glu
675 680 685
Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr
690 695 700
Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys
705 710 715 720
Leu Glu Gln Arg Val Lys Arg Trp Lys Asp Ser Tyr Gln Trp Met Val
725 730 735
Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln Phe Asn His Ile Asn Tyr
740 745 750
Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys
755 760 765
Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile
770 775 780
Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp Val Lys Ile Ser
785 790 795 800
Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu Cys Ser Val Thr
805 810 815
Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp Glu Leu Asn Lys
820 825 830
Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile Asn Leu Ile Asp Ser His
835 840 845
Asn Ile Ile Leu Val Gly Glu Val Asp Arg Leu Lys Ala Lys Val Asn
850 855 860
Glu Ser Phe Glu Asn Thr Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn
865 870 875 880
Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe Asn
885 890
<210> 54
<211> 902
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 54
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Lys Ser Glu Glu Lys Leu Tyr Asp Asp Asp
435 440 445
Asp Lys Asp Arg Trp Gly Ser Ser Leu Gln Cys Ile Lys Val Lys Asn
450 455 460
Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile
465 470 475 480
Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser
485 490 495
Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile
500 505 510
Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro
515 520 525
Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys
530 535 540
Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu
545 550 555 560
Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala
565 570 575
Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu
580 585 590
Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn
595 600 605
Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu
610 615 620
Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala
625 630 635 640
Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe
645 650 655
Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr
660 665 670
Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg
675 680 685
Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys
690 695 700
Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg
705 710 715 720
Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu
725 730 735
Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys
740 745 750
Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn
755 760 765
Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile
770 775 780
Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met
785 790 795 800
Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys
805 810 815
Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly
820 825 830
Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr
835 840 845
Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp
850 855 860
Ile Ile Asn Glu Tyr Phe Asn Leu Glu Gly Gly Gly Gly Ser Gly Gly
865 870 875 880
Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Tyr Asn Trp Asn Ser
885 890 895
Phe Gly Leu Arg Phe Gly
900
<210> 55
<211> 905
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 55
Glu Phe Val Asn Lys Gln Phe Asn Tyr Lys Asp Pro Val Asn Gly Val
1 5 10 15
Asp Ile Ala Tyr Ile Lys Ile Pro Asn Ala Gly Gln Met Gln Pro Val
20 25 30
Lys Ala Phe Lys Ile His Asn Lys Ile Trp Val Ile Pro Glu Arg Asp
35 40 45
Thr Phe Thr Asn Pro Glu Glu Gly Asp Leu Asn Pro Pro Pro Glu Ala
50 55 60
Lys Gln Val Pro Val Ser Tyr Tyr Asp Ser Thr Tyr Leu Ser Thr Asp
65 70 75 80
Asn Glu Lys Asp Asn Tyr Leu Lys Gly Val Thr Lys Leu Phe Glu Arg
85 90 95
Ile Tyr Ser Thr Asp Leu Gly Arg Met Leu Leu Thr Ser Ile Val Arg
100 105 110
Gly Ile Pro Phe Trp Gly Gly Ser Thr Ile Asp Thr Glu Leu Lys Val
115 120 125
Ile Asp Thr Asn Cys Ile Asn Val Ile Gln Pro Asp Gly Ser Tyr Arg
130 135 140
Ser Glu Glu Leu Asn Leu Val Ile Ile Gly Pro Ser Ala Asp Ile Ile
145 150 155 160
Gln Phe Glu Cys Lys Ser Phe Gly His Glu Val Leu Asn Leu Thr Arg
165 170 175
Asn Gly Tyr Gly Ser Thr Gln Tyr Ile Arg Phe Ser Pro Asp Phe Thr
180 185 190
Phe Gly Phe Glu Glu Ser Leu Glu Val Asp Thr Asn Pro Leu Leu Gly
195 200 205
Ala Gly Lys Phe Ala Thr Asp Pro Ala Val Thr Leu Ala His Glu Leu
210 215 220
Ile His Ala Gly His Arg Leu Tyr Gly Ile Ala Ile Asn Pro Asn Arg
225 230 235 240
Val Phe Lys Val Asn Thr Asn Ala Tyr Tyr Glu Met Ser Gly Leu Glu
245 250 255
Val Ser Phe Glu Glu Leu Arg Thr Phe Gly Gly His Asp Ala Lys Phe
260 265 270
Ile Asp Ser Leu Gln Glu Asn Glu Phe Arg Leu Tyr Tyr Tyr Asn Lys
275 280 285
Phe Lys Asp Ile Ala Ser Thr Leu Asn Lys Ala Lys Ser Ile Val Gly
290 295 300
Thr Thr Ala Ser Leu Gln Tyr Met Lys Asn Val Phe Lys Glu Lys Tyr
305 310 315 320
Leu Leu Ser Glu Asp Thr Ser Gly Lys Phe Ser Val Asp Lys Leu Lys
325 330 335
Phe Asp Lys Leu Tyr Lys Met Leu Thr Glu Ile Tyr Thr Glu Asp Asn
340 345 350
Phe Val Lys Phe Phe Lys Val Leu Asn Arg Lys Thr Tyr Leu Asn Phe
355 360 365
Asp Lys Ala Val Phe Lys Ile Asn Ile Val Pro Lys Val Asn Tyr Thr
370 375 380
Ile Tyr Asp Gly Phe Asn Leu Arg Asn Thr Asn Leu Ala Ala Asn Phe
385 390 395 400
Asn Gly Gln Asn Thr Glu Ile Asn Asn Met Asn Phe Thr Lys Leu Lys
405 410 415
Asn Phe Thr Gly Leu Phe Glu Phe Tyr Lys Leu Leu Cys Val Asp Gly
420 425 430
Ile Ile Thr Ser Lys Thr Lys Ser Asp Asp Asp Asp Lys Asn Lys Ala
435 440 445
Leu Asn Leu Gln Cys Ile Lys Val Asn Asn Trp Asp Leu Phe Phe Ser
450 455 460
Pro Ser Glu Asp Asn Phe Thr Asn Asp Leu Asn Lys Gly Glu Glu Ile
465 470 475 480
Thr Ser Asp Thr Asn Ile Glu Ala Ala Glu Glu Asn Ile Ser Leu Asp
485 490 495
Leu Ile Gln Gln Tyr Tyr Leu Thr Phe Asn Phe Asp Asn Glu Pro Glu
500 505 510
Asn Ile Ser Ile Glu Asn Leu Ser Ser Asp Ile Ile Gly Gln Leu Glu
515 520 525
Leu Met Pro Asn Ile Glu Arg Phe Pro Asn Gly Lys Lys Tyr Glu Leu
530 535 540
Asp Lys Tyr Thr Met Phe His Tyr Leu Arg Ala Gln Glu Phe Glu His
545 550 555 560
Gly Lys Ser Arg Ile Ala Leu Thr Asn Ser Val Asn Glu Ala Leu Leu
565 570 575
Asn Pro Ser Arg Val Tyr Thr Phe Phe Ser Ser Asp Tyr Val Lys Lys
580 585 590
Val Asn Lys Ala Thr Glu Ala Ala Met Phe Leu Gly Trp Val Glu Gln
595 600 605
Leu Val Tyr Asp Phe Thr Asp Glu Thr Ser Glu Val Ser Thr Thr Asp
610 615 620
Lys Ile Ala Asp Ile Thr Ile Ile Ile Pro Tyr Ile Gly Pro Ala Leu
625 630 635 640
Asn Ile Gly Asn Met Leu Tyr Lys Asp Asp Phe Val Gly Ala Leu Ile
645 650 655
Phe Ser Gly Ala Val Ile Leu Leu Glu Phe Ile Pro Glu Ile Ala Ile
660 665 670
Pro Val Leu Gly Thr Phe Ala Leu Val Ser Tyr Ile Ala Asn Lys Val
675 680 685
Leu Thr Val Gln Thr Ile Asp Asn Ala Leu Ser Lys Arg Asn Glu Lys
690 695 700
Trp Asp Glu Val Tyr Lys Tyr Ile Val Thr Asn Trp Leu Ala Lys Val
705 710 715 720
Asn Thr Gln Ile Asp Leu Ile Arg Lys Lys Met Lys Glu Ala Leu Glu
725 730 735
Asn Gln Ala Glu Ala Thr Lys Ala Ile Ile Asn Tyr Gln Tyr Asn Gln
740 745 750
Tyr Thr Glu Glu Glu Lys Asn Asn Ile Asn Phe Asn Ile Asp Asp Leu
755 760 765
Ser Ser Lys Leu Asn Glu Ser Ile Asn Lys Ala Met Ile Asn Ile Asn
770 775 780
Lys Phe Leu Asn Gln Cys Ser Val Ser Tyr Leu Met Asn Ser Met Ile
785 790 795 800
Pro Tyr Gly Val Lys Arg Leu Glu Asp Phe Asp Ala Ser Leu Lys Asp
805 810 815
Ala Leu Leu Lys Tyr Ile Tyr Asp Asn Arg Gly Thr Leu Ile Gly Gln
820 825 830
Val Asp Arg Leu Lys Asp Lys Val Asn Asn Thr Leu Ser Thr Asp Ile
835 840 845
Pro Phe Gln Leu Ser Lys Tyr Val Asp Asn Gln Arg Leu Leu Ser Thr
850 855 860
Leu Glu Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
865 870 875 880
Ser Ala Leu Val Thr Pro Asp Ile Asn Pro Ala Trp Tyr Ala Ser Arg
885 890 895
Gly Ile Arg Pro Val Gly Arg Phe Gly
900 905
<210> 56
<211> 927
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 56
Pro Ile Thr Ile Asn Asn Phe Asn Tyr Ser Asp Pro Val Asp Asn Lys
1 5 10 15
Asn Ile Leu Tyr Leu Asp Thr His Leu Asn Thr Leu Ala Asn Glu Pro
20 25 30
Glu Lys Ala Phe Arg Ile Thr Gly Asn Ile Trp Val Ile Pro Asp Arg
35 40 45
Phe Ser Arg Asn Ser Asn Pro Asn Leu Asn Lys Pro Pro Arg Val Thr
50 55 60
Ser Pro Lys Ser Gly Tyr Tyr Asp Pro Asn Tyr Leu Ser Thr Asp Ser
65 70 75 80
Asp Lys Asp Thr Phe Leu Lys Glu Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Ser Arg Glu Ile Gly Glu Glu Leu Ile Tyr Arg Leu Ser Thr Asp
100 105 110
Ile Pro Phe Pro Gly Asn Asn Asn Thr Pro Ile Asn Thr Phe Asp Phe
115 120 125
Asp Val Asp Phe Asn Ser Val Asp Val Lys Thr Arg Gln Gly Asn Asn
130 135 140
Trp Val Lys Thr Gly Ser Ile Asn Pro Ser Val Ile Ile Thr Gly Pro
145 150 155 160
Arg Glu Asn Ile Ile Asp Pro Glu Thr Ser Thr Phe Lys Leu Thr Asn
165 170 175
Asn Thr Phe Ala Ala Gln Glu Gly Phe Gly Ala Leu Ser Ile Ile Ser
180 185 190
Ile Ser Pro Arg Phe Met Leu Thr Tyr Ser Asn Ala Thr Asn Asp Val
195 200 205
Gly Glu Gly Arg Phe Ser Lys Ser Glu Phe Cys Met Asp Pro Ile Leu
210 215 220
Ile Leu Met His Glu Leu Asn His Ala Met His Asn Leu Tyr Gly Ile
225 230 235 240
Ala Ile Pro Asn Asp Gln Thr Ile Ser Ser Val Thr Ser Asn Ile Phe
245 250 255
Tyr Ser Gln Tyr Asn Val Lys Leu Glu Tyr Ala Glu Ile Tyr Ala Phe
260 265 270
Gly Gly Pro Thr Ile Asp Leu Ile Pro Lys Ser Ala Arg Lys Tyr Phe
275 280 285
Glu Glu Lys Ala Leu Asp Tyr Tyr Arg Ser Ile Ala Lys Arg Leu Asn
290 295 300
Ser Ile Thr Thr Ala Asn Pro Ser Ser Phe Asn Lys Tyr Ile Gly Glu
305 310 315 320
Tyr Lys Gln Lys Leu Ile Arg Lys Tyr Arg Phe Val Val Glu Ser Ser
325 330 335
Gly Glu Val Thr Val Asn Arg Asn Lys Phe Val Glu Leu Tyr Asn Glu
340 345 350
Leu Thr Gln Ile Phe Thr Glu Phe Asn Tyr Ala Lys Ile Tyr Asn Val
355 360 365
Gln Asn Arg Lys Ile Tyr Leu Ser Asn Val Tyr Thr Pro Val Thr Ala
370 375 380
Asn Ile Leu Asp Asp Asn Val Tyr Asp Ile Gln Asn Gly Phe Asn Ile
385 390 395 400
Pro Lys Ser Asn Leu Asn Val Leu Phe Met Gly Gln Asn Leu Ser Arg
405 410 415
Asn Pro Ala Leu Arg Lys Val Asn Pro Glu Asn Met Leu Tyr Leu Phe
420 425 430
Thr Lys Phe Cys Val Asp Gly Gly Gly Gly Ser Ala Asp Asp Asp Asp
435 440 445
Lys Ser Glu Glu Pro Pro Ile Ser Leu Asp Leu Thr Phe His Leu Leu
450 455 460
Arg Glu Val Leu Glu Met Ala Arg Ala Glu Gln Leu Ala Gln Gln Ala
465 470 475 480
His Ser Asn Arg Lys Leu Met Glu Ile Ile Ala Leu Ala Gly Gly Gly
485 490 495
Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Val Leu
500 505 510
Gln Cys Arg Glu Leu Leu Val Lys Asn Thr Asp Leu Pro Phe Ile Gly
515 520 525
Asp Ile Ser Asp Val Lys Thr Asp Ile Phe Leu Arg Lys Asp Ile Asn
530 535 540
Glu Glu Thr Glu Val Ile Tyr Tyr Pro Asp Asn Val Ser Val Asp Gln
545 550 555 560
Val Ile Leu Ser Lys Asn Thr Ser Glu His Gly Gln Leu Asp Leu Leu
565 570 575
Tyr Pro Ser Ile Asp Ser Glu Ser Glu Ile Leu Pro Gly Glu Asn Gln
580 585 590
Val Phe Tyr Asp Asn Arg Thr Gln Asn Val Asp Tyr Leu Asn Ser Tyr
595 600 605
Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asp Asn Val Glu Asp Phe Thr
610 615 620
Phe Thr Arg Ser Ile Glu Glu Ala Leu Asp Asn Ser Ala Lys Val Tyr
625 630 635 640
Thr Tyr Phe Pro Thr Leu Ala Asn Lys Val Asn Ala Gly Val Gln Gly
645 650 655
Gly Leu Phe Leu Met Trp Ala Asn Asp Val Val Glu Asp Phe Thr Thr
660 665 670
Asn Ile Leu Arg Lys Asp Thr Leu Asp Lys Ile Ser Asp Val Ser Ala
675 680 685
Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Ser Asn Ser Val Arg
690 695 700
Arg Gly Asn Phe Thr Glu Ala Phe Ala Val Thr Gly Val Thr Ile Leu
705 710 715 720
Leu Glu Ala Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Ala Phe Val
725 730 735
Ile Tyr Ser Lys Val Gln Glu Arg Asn Glu Ile Ile Lys Thr Ile Asp
740 745 750
Asn Cys Leu Glu Gln Arg Ile Lys Arg Trp Lys Asp Ser Tyr Glu Trp
755 760 765
Met Met Gly Thr Trp Leu Ser Arg Ile Ile Thr Gln Phe Asn Asn Ile
770 775 780
Ser Tyr Gln Met Tyr Asp Ser Leu Asn Tyr Gln Ala Gly Ala Ile Lys
785 790 795 800
Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp Lys Glu
805 810 815
Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp Val Lys
820 825 830
Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu Cys Ser
835 840 845
Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp Glu Leu
850 855 860
Asn Glu Phe Asp Arg Asn Thr Lys Ala Lys Leu Ile Asn Leu Ile Asp
865 870 875 880
Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Lys Leu Lys Ala Lys
885 890 895
Val Asn Asn Ser Phe Gln Asn Thr Ile Pro Phe Asn Ile Phe Ser Tyr
900 905 910
Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe Asn
915 920 925
<210> 57
<211> 915
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 57
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ala
465 470 475 480
Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
485 490 495
Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu Pro
500 505 510
Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys
515 520 525
Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser
530 535 540
Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu Ile
545 550 555 560
Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu Pro
565 570 575
Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr
580 585 590
Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn Val
595 600 605
Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser
610 615 620
Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn Lys
625 630 635 640
Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val Glu
645 650 655
Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile Ser
660 665 670
Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly
675 680 685
Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly
690 695 700
Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu
705 710 715 720
Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile
725 730 735
Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys Asp
740 745 750
Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln
755 760 765
Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala
770 775 780
Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly
785 790 795 800
Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser
805 810 815
Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile
820 825 830
Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val
835 840 845
Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile
850 855 860
Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Arg
865 870 875 880
Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe Asn
885 890 895
Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu
900 905 910
Tyr Phe Asn
915
<210> 58
<211> 916
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 58
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
485 490 495
Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu
500 505 510
Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn
515 520 525
Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe
530 535 540
Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu
545 550 555 560
Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu
565 570 575
Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp
580 585 590
Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn
595 600 605
Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr
610 615 620
Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn
625 630 635 640
Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val
645 650 655
Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile
660 665 670
Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile
675 680 685
Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala
690 695 700
Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala
705 710 715 720
Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile
725 730 735
Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys
740 745 750
Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr
755 760 765
Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln
770 775 780
Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser
785 790 795 800
Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn
805 810 815
Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe
820 825 830
Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys
835 840 845
Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu
850 855 860
Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp
865 870 875 880
Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe
885 890 895
Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn
900 905 910
Glu Tyr Phe Asn
915
<210> 59
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 59
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 60
<211> 932
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 60
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Gln Gln Gly Glu Ser Asn Gln Glu Arg Gly Ala Arg Ala Arg Leu
485 490 495
Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
500 505 510
Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu
515 520 525
Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn
530 535 540
Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe
545 550 555 560
Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu
565 570 575
Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu
580 585 590
Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp
595 600 605
Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn
610 615 620
Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr
625 630 635 640
Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn
645 650 655
Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val
660 665 670
Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile
675 680 685
Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile
690 695 700
Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala
705 710 715 720
Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala
725 730 735
Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile
740 745 750
Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys
755 760 765
Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr
770 775 780
Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln
785 790 795 800
Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser
805 810 815
Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn
820 825 830
Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe
835 840 845
Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys
850 855 860
Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu
865 870 875 880
Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp
885 890 895
Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe
900 905 910
Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn
915 920 925
Glu Tyr Phe Asn
930
<210> 61
<211> 927
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 61
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Gln Gln Gly Glu Ser Asn Gln Glu Arg Gly Ala Leu Ala Gly Gly
485 490 495
Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Ala Leu Ala
500 505 510
Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu Pro Tyr Val Ala Asp
515 520 525
Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys Ile Ile Thr Asp
530 535 540
Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser Leu Asp Glu Ser
545 550 555 560
Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu Ile Val Asp Pro Leu
565 570 575
Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu Pro Gly Glu Glu Ile
580 585 590
Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr Leu Asn Ser Tyr
595 600 605
Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn Val Glu Asn Ile Thr
610 615 620
Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser Asn Lys Ile Tyr
625 630 635 640
Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn Lys Gly Val Gln Ala
645 650 655
Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val Glu Asp Phe Thr Thr
660 665 670
Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile Ser Asp Val Ser Val
675 680 685
Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly Asn Ser Ala Leu
690 695 700
Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly Val Ala Phe Leu
705 710 715 720
Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu Gly Val Phe Thr
725 730 735
Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile Lys Thr Ile Glu
740 745 750
Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys Asp Ser Tyr Gln Trp
755 760 765
Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln Phe Asn His Ile
770 775 780
Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala Asp Ala Ile Lys
785 790 795 800
Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly Ser Asp Lys Glu
805 810 815
Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser Leu Asp Val Lys
820 825 830
Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile Arg Glu Cys Ser
835 840 845
Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val Ile Asp Glu Leu
850 855 860
Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile Asn Leu Ile Asp
865 870 875 880
Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Arg Leu Lys Ala Lys
885 890 895
Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe Asn Ile Phe Ser Tyr
900 905 910
Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu Tyr Phe Asn
915 920 925
<210> 62
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 62
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ala Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 63
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 63
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Ala Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 64
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 64
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Lys Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 65
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 65
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Lys Arg
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 66
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 66
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Asn Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 67
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 67
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Lys Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 68
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 68
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Lys Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Lys Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 69
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 69
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Asn Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 70
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 70
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Asn
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 71
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 71
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Asn Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 72
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 72
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Glu Ala Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 73
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 73
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Glu Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 74
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 74
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys
450 455 460
Glu Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 75
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 75
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 76
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 76
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Glu Ser Tyr Arg Lys
450 455 460
Val Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 77
<211> 915
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 77
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ala
465 470 475 480
Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly Gly
485 490 495
Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu Pro
500 505 510
Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn Lys
515 520 525
Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe Ser
530 535 540
Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu Ile
545 550 555 560
Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu Pro
565 570 575
Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp Tyr
580 585 590
Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn Val
595 600 605
Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr Ser
610 615 620
Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn Lys
625 630 635 640
Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val Glu
645 650 655
Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile Ser
660 665 670
Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile Gly
675 680 685
Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala Gly
690 695 700
Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala Leu
705 710 715 720
Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile Ile
725 730 735
Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys Asp
740 745 750
Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr Gln
755 760 765
Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln Ala
770 775 780
Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser Gly
785 790 795 800
Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn Ser
805 810 815
Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe Ile
820 825 830
Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys Val
835 840 845
Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu Ile
850 855 860
Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp Arg
865 870 875 880
Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe Asn
885 890 895
Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn Glu
900 905 910
Tyr Phe Asn
915
<210> 78
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 78
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Asn Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 79
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 79
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 80
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 80
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ala Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Ala Leu Gln Asp Ile Ala Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 81
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 81
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Ala Ala Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Ala Leu Gln Asp Ile Met Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 82
<211> 920
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 82
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Gln Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Ala Leu Gln Asp Ile Leu Ser
465 470 475 480
Arg Gln Gln Gly Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly
485 490 495
Ser Gly Gly Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys
500 505 510
Asn Asn Arg Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu
515 520 525
Ile Phe Glu Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr
530 535 540
Ser Asp Lys Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro
545 550 555 560
Ile Asn Pro Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu
565 570 575
Pro Leu Asn Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr
580 585 590
Lys Tyr Val Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys
595 600 605
Leu Ser Asn Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu
610 615 620
Ala Leu Gly Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala
625 630 635 640
Glu Lys Val Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala
645 650 655
Asn Glu Val Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr
660 665 670
Leu Asp Lys Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro
675 680 685
Ala Leu Asn Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala
690 695 700
Phe Ala Thr Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe
705 710 715 720
Thr Ile Pro Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu
725 730 735
Arg Glu Lys Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val
740 745 750
Lys Arg Trp Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser
755 760 765
Arg Ile Thr Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser
770 775 780
Leu Ser Tyr Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr
785 790 795 800
Lys Lys Tyr Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu
805 810 815
Asn Leu Lys Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn
820 825 830
Ile Asn Lys Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn
835 840 845
Met Leu Pro Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr
850 855 860
Lys Thr Glu Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val
865 870 875 880
Gly Glu Val Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn
885 890 895
Thr Met Pro Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys
900 905 910
Asp Ile Ile Asn Glu Tyr Phe Asn
915 920
<210> 83
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 83
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Ser Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 84
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 84
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys His Val Asp Ala Ile Phe Thr Thr Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 85
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 85
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Gln Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Ala Leu Gln Asp Ile Leu Asn
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 86
<211> 917
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 86
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Asp
435 440 445
Asp Asp Asp Lys Tyr Ala Asp Ala Ile Phe Thr Gln Ser Tyr Arg Lys
450 455 460
Val Leu Ala Gln Leu Ser Ala Arg Lys Ala Leu Gln Asp Ile Leu Ser
465 470 475 480
Arg Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly
485 490 495
Gly Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg
500 505 510
Leu Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu
515 520 525
Asn Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys
530 535 540
Phe Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro
545 550 555 560
Glu Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn
565 570 575
Leu Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val
580 585 590
Asp Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn
595 600 605
Asn Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly
610 615 620
Tyr Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val
625 630 635 640
Asn Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val
645 650 655
Val Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys
660 665 670
Ile Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn
675 680 685
Ile Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr
690 695 700
Ala Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro
705 710 715 720
Ala Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys
725 730 735
Ile Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp
740 745 750
Lys Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr
755 760 765
Thr Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr
770 775 780
Gln Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr
785 790 795 800
Ser Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys
805 810 815
Asn Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys
820 825 830
Phe Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro
835 840 845
Lys Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu
850 855 860
Leu Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val
865 870 875 880
Asp Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro
885 890 895
Phe Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile
900 905 910
Asn Glu Tyr Phe Asn
915
<210> 87
<211> 916
<212> PRT
<213> 人工序列
<220>
<221> 来源
<223> /注释="人工序列的描述: 合成的
多肽"
<400> 87
Thr Trp Pro Val Lys Asp Phe Asn Tyr Ser Asp Pro Val Asn Asp Asn
1 5 10 15
Asp Ile Leu Tyr Leu Arg Ile Pro Gln Asn Lys Leu Ile Thr Thr Pro
20 25 30
Val Lys Ala Phe Met Ile Thr Gln Asn Ile Trp Val Ile Pro Glu Arg
35 40 45
Phe Ser Ser Asp Thr Asn Pro Ser Leu Ser Lys Pro Pro Arg Pro Thr
50 55 60
Ser Lys Tyr Gln Ser Tyr Tyr Asp Pro Ser Tyr Leu Ser Thr Asp Glu
65 70 75 80
Gln Lys Asp Thr Phe Leu Lys Gly Ile Ile Lys Leu Phe Lys Arg Ile
85 90 95
Asn Glu Arg Asp Ile Gly Lys Lys Leu Ile Asn Tyr Leu Val Val Gly
100 105 110
Ser Pro Phe Met Gly Asp Ser Ser Thr Pro Glu Asp Thr Phe Asp Phe
115 120 125
Thr Arg His Thr Thr Asn Ile Ala Val Glu Lys Phe Glu Asn Gly Ser
130 135 140
Trp Lys Val Thr Asn Ile Ile Thr Pro Ser Val Leu Ile Phe Gly Pro
145 150 155 160
Leu Pro Asn Ile Leu Asp Tyr Thr Ala Ser Leu Thr Leu Gln Gly Gln
165 170 175
Gln Ser Asn Pro Ser Phe Glu Gly Phe Gly Thr Leu Ser Ile Leu Lys
180 185 190
Val Ala Pro Glu Phe Leu Leu Thr Phe Ser Asp Val Thr Ser Asn Gln
195 200 205
Ser Ser Ala Val Leu Gly Lys Ser Ile Phe Cys Met Asp Pro Val Ile
210 215 220
Ala Leu Met His Glu Leu Thr His Ser Leu His Gln Leu Tyr Gly Ile
225 230 235 240
Asn Ile Pro Ser Asp Lys Arg Ile Arg Pro Gln Val Ser Glu Gly Phe
245 250 255
Phe Ser Gln Asp Gly Pro Asn Val Gln Phe Glu Glu Leu Tyr Thr Phe
260 265 270
Gly Gly Leu Asp Val Glu Ile Ile Pro Gln Ile Glu Arg Ser Gln Leu
275 280 285
Arg Glu Lys Ala Leu Gly His Tyr Lys Asp Ile Ala Lys Arg Leu Asn
290 295 300
Asn Ile Asn Lys Thr Ile Pro Ser Ser Trp Ile Ser Asn Ile Asp Lys
305 310 315 320
Tyr Lys Lys Ile Phe Ser Glu Lys Tyr Asn Phe Asp Lys Asp Asn Thr
325 330 335
Gly Asn Phe Val Val Asn Ile Asp Lys Phe Asn Ser Leu Tyr Ser Asp
340 345 350
Leu Thr Asn Val Met Ser Glu Val Val Tyr Ser Ser Gln Tyr Asn Val
355 360 365
Lys Asn Arg Thr His Tyr Phe Ser Arg His Tyr Leu Pro Val Phe Ala
370 375 380
Asn Ile Leu Asp Asp Asn Ile Tyr Thr Ile Arg Asp Gly Phe Asn Leu
385 390 395 400
Thr Asn Lys Gly Phe Asn Ile Glu Asn Ser Gly Gln Asn Ile Glu Arg
405 410 415
Asn Pro Ala Leu Gln Lys Leu Ser Ser Glu Ser Val Val Asp Leu Phe
420 425 430
Thr Lys Val Cys Val Asp Gly Ile Ile Thr Ser Lys Thr Lys Ser Ile
435 440 445
Glu Gly Arg Tyr Ala Asp Ala Ile Phe Thr Ala Ser Tyr Arg Lys Val
450 455 460
Leu Gly Gln Leu Ser Ala Arg Lys Leu Leu Gln Asp Ile Leu Ser Arg
465 470 475 480
Ala Leu Ala Gly Gly Gly Gly Ser Gly Gly Gly Gly Ser Gly Gly Gly
485 490 495
Gly Ser Ala Leu Ala Leu Gln Cys Ile Lys Val Lys Asn Asn Arg Leu
500 505 510
Pro Tyr Val Ala Asp Lys Asp Ser Ile Ser Gln Glu Ile Phe Glu Asn
515 520 525
Lys Ile Ile Thr Asp Glu Thr Asn Val Gln Asn Tyr Ser Asp Lys Phe
530 535 540
Ser Leu Asp Glu Ser Ile Leu Asp Gly Gln Val Pro Ile Asn Pro Glu
545 550 555 560
Ile Val Asp Pro Leu Leu Pro Asn Val Asn Met Glu Pro Leu Asn Leu
565 570 575
Pro Gly Glu Glu Ile Val Phe Tyr Asp Asp Ile Thr Lys Tyr Val Asp
580 585 590
Tyr Leu Asn Ser Tyr Tyr Tyr Leu Glu Ser Gln Lys Leu Ser Asn Asn
595 600 605
Val Glu Asn Ile Thr Leu Thr Thr Ser Val Glu Glu Ala Leu Gly Tyr
610 615 620
Ser Asn Lys Ile Tyr Thr Phe Leu Pro Ser Leu Ala Glu Lys Val Asn
625 630 635 640
Lys Gly Val Gln Ala Gly Leu Phe Leu Asn Trp Ala Asn Glu Val Val
645 650 655
Glu Asp Phe Thr Thr Asn Ile Met Lys Lys Asp Thr Leu Asp Lys Ile
660 665 670
Ser Asp Val Ser Val Ile Ile Pro Tyr Ile Gly Pro Ala Leu Asn Ile
675 680 685
Gly Asn Ser Ala Leu Arg Gly Asn Phe Asn Gln Ala Phe Ala Thr Ala
690 695 700
Gly Val Ala Phe Leu Leu Glu Gly Phe Pro Glu Phe Thr Ile Pro Ala
705 710 715 720
Leu Gly Val Phe Thr Phe Tyr Ser Ser Ile Gln Glu Arg Glu Lys Ile
725 730 735
Ile Lys Thr Ile Glu Asn Cys Leu Glu Gln Arg Val Lys Arg Trp Lys
740 745 750
Asp Ser Tyr Gln Trp Met Val Ser Asn Trp Leu Ser Arg Ile Thr Thr
755 760 765
Gln Phe Asn His Ile Asn Tyr Gln Met Tyr Asp Ser Leu Ser Tyr Gln
770 775 780
Ala Asp Ala Ile Lys Ala Lys Ile Asp Leu Glu Tyr Lys Lys Tyr Ser
785 790 795 800
Gly Ser Asp Lys Glu Asn Ile Lys Ser Gln Val Glu Asn Leu Lys Asn
805 810 815
Ser Leu Asp Val Lys Ile Ser Glu Ala Met Asn Asn Ile Asn Lys Phe
820 825 830
Ile Arg Glu Cys Ser Val Thr Tyr Leu Phe Lys Asn Met Leu Pro Lys
835 840 845
Val Ile Asp Glu Leu Asn Lys Phe Asp Leu Arg Thr Lys Thr Glu Leu
850 855 860
Ile Asn Leu Ile Asp Ser His Asn Ile Ile Leu Val Gly Glu Val Asp
865 870 875 880
Arg Leu Lys Ala Lys Val Asn Glu Ser Phe Glu Asn Thr Met Pro Phe
885 890 895
Asn Ile Phe Ser Tyr Thr Asn Asn Ser Leu Leu Lys Asp Ile Ile Asn
900 905 910
Glu Tyr Phe Asn
915

Claims (19)

1.一种多肽，所述多肽应用于抑制癌症，所述多肽包括：
a.非细胞毒性蛋白酶，所述蛋白酶能够在生长激素分泌细胞中切割细胞外融合器的蛋白；
b.靶向部分(TM)，其与生长激素分泌细胞上的结合位点结合，所述结合位点能够经历胞吞作用以被并入所述生长激素分泌细胞的内体；和
c.易位结构域，其从所述内体内、跨内体膜和进入所述生长激素分泌细胞的胞质溶胶中易位所述蛋白酶。
2.根据权利要求1应用的多肽，其中所述生长激素分泌细胞是垂体细胞。
3.根据权利要求1或权利要求2应用的多肽，其中所述TM结合选自由以下组成的组的受体：生长激素释放激素(GHRH)受体、瘦蛋白(OB)受体、生长素释放肽受体、促生长素抑制素(sst)受体、胰岛素生长因子(IGF)受体、ErbB受体、VIP-胰高血糖素-GRF-促胰液素超家族受体、食欲肽(OX)受体、白介素(IL)受体、神经生长因子(NTR)受体、血管内皮生长因子(VEGF)受体、铃蟾肽受体、硬骨鱼紧张肽受体、黑色素浓缩激素受体1、促乳素释放激素受体、KiSS-1受体或促肾上腺皮质素释放因子受体1。
4.根据任一前述权利要求应用的多肽，其中所述TM选自由以下组成的组：生长激素释放激素(GHRH)肽、瘦蛋白肽、生长素释放肽、促生长素抑制素(SST)肽、皮质抑素肽、胰岛素样生长因子(IGF)肽、转化生长因子(TGF)肽、VIP-胰高血糖素-GRF-促胰液素超家族肽、PACAP肽、血管活性肠肽(VIP)、食欲肽、白介素肽、神经生长因子(NGF)肽、血管内皮生长因子(VEGF)肽、甲状腺激素肽、雌激素肽、ErbB肽、表皮生长因子(EGF)肽、EGF和TGF-α嵌合肽、双调蛋白肽、β细胞调节素肽、epigen肽、表皮调节素肽、肝素结合EGF(HB-EGF)肽、铃蟾肽、硬骨鱼紧张肽、黑色素浓缩激素(MCH)肽、促乳素释放肽、Kisspeptin-10肽、Kisspeptin-54肽、促肾上腺皮质素释放激素肽、尿皮质素1肽或尿皮质素2肽。
5.根据任一前述权利要求应用的多肽，其中所述非细胞毒性蛋白酶包括梭菌神经毒素内肽酶。
6.根据权利要求1-4任一项应用的多肽，其中所述非细胞毒性蛋白酶包括IgA蛋白酶。
7.根据任一前述权利要求应用的多肽，其中所述易位结构域包括梭菌神经毒素易位结构域。
8.一种多肽，包括：
a.非细胞毒性蛋白酶，所述蛋白酶能够在生长激素分泌细胞中切割细胞外融合器的蛋白；
b.靶向部分(TM)，其与生长激素分泌细胞上的结合位点结合，所述结合位点能够经历胞吞作用以被并入所述生长激素分泌细胞的内体；和
c.易位结构域，其从所述内体内、跨内体膜和进入所述生长激素分泌细胞的胞质溶胶中易位所述蛋白酶。
9.根据权利要求8所述的多肽，其中所述生长激素分泌细胞是垂体细胞。
10.根据权利要求8或权利要求9所述的多肽，其中所述TM结合选自由以下组成的组的受体：生长激素释放激素(GHRH)受体、瘦蛋白(OB)受体、生长素释放肽受体、促生长素抑制素(sst)受体、胰岛素生长因子(IGF)受体、ErbB受体、VIP-胰高血糖素-GRF-促胰液素超家族受体、食欲肽(OX)受体、白介素(IL)受体、神经生长因子(NTR)受体、血管内皮生长因子(VEGF)受体、铃蟾肽受体、硬骨鱼紧张肽受体、黑色素浓缩激素受体1、促乳素释放激素受体、KiSS-1受体或促肾上腺皮质素释放因子受体1。
11.根据权利要求8-10任一项所述的多肽，其中所述TM选自由以下组成的组：生长激素释放激素(GHRH)肽、瘦蛋白肽、生长素释放肽、促生长素抑制素(SST)肽、皮质抑素肽、胰岛素样生长因子(IGF)肽、转化生长因子(TGF)肽、VIP-胰高血糖素-GRF-促胰液素超家族肽、PACAP肽、血管活性肠肽(VIP)、食欲肽、白介素肽、神经生长因子(NGF)肽、血管内皮生长因子(VEGF)肽、甲状腺激素肽、雌激素肽、ErbB肽、表皮生长因子(EGF)肽、EGF和TGF-α嵌合肽、双调蛋白肽、β细胞调节素肽、epigen肽、表皮调节素肽、肝素结合EGF(HB-EGF)肽、铃蟾肽、硬骨鱼紧张肽、黑色素浓缩激素(MCH)肽、促乳素释放肽、Kisspeptin-10肽、Kisspeptin-54肽、促肾上腺皮质素释放激素肽、尿皮质素1肽或尿皮质素2肽。
12.根据权利要求8-11任一项所述的多肽，其中所述非细胞毒性蛋白酶包括梭菌神经毒素内肽酶。
13.根据权利要求8-11任一项所述的多肽，其中所述非细胞毒性蛋白酶包括IgA蛋白酶。
14.根据权利要求8-13任一项所述的多肽，其中所述易位结构域包括梭菌神经毒素易位结构域。
15.根据权利要求8所述的多肽，其中所述多肽包括与SEQ ID NO:8、9、10、11、12、13、14、15、16、17、18、19、20、21、22、23、24、25、26、27、28、29、30、33、34、35、36、37、38、39、40、41、42、43、44、53、54、55、56、57、58、59、60、61、62、63、64、65、66、67、68、69、70、71、72、73、74、75、76、77、78、79、80、81、82、83、84、85、86、87的任一个具有至少90-92％、或至少95-97％、或至少98-99％序列同一性的氨基酸序列。
16.一种核酸序列，所述核酸序列编码根据权利要求8-15任一项的多肽。
17.一种核酸，所述核酸编码根据权利要求8的多肽，其中所述核酸包括与SEQ ID NO:7和32的任一个具有至少90-94％、或至少95-97％、或至少98-99％序列同一性的核酸序列。
18.一种抑制患者癌症的方法，包括向患者施用有效量的根据权利要求8-15任一项的多肽或根据权利要求16或17的核酸。
19.根据权利要求1-7任一项的应用或者根据权利要求18的方法，用于抑制选自由以下组成的组的一种或多种癌症：前列腺癌、肺癌、乳腺癌或结肠直肠癌。
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AU2009259034B2 (en) 2013-10-31
US20140219983A1 (en) 2014-08-07
KR101731655B1 (ko) 2017-05-11
BRPI0915142A8 (pt) 2018-01-02
EP2310029B1 (en) 2019-04-03
CA2726092A1 (en) 2009-12-17
JP5799397B2 (ja) 2015-10-28
ES2732205T3 (es) 2019-11-21
IL209854A0 (en) 2011-02-28
WO2009150470A3 (en) 2010-07-15
US10240138B2 (en) 2019-03-26
US10550377B2 (en) 2020-02-04
US20110165137A1 (en) 2011-07-07
HK1246809A1 (zh) 2018-09-14
CN102083451A (zh) 2011-06-01
ZA201008425B (en) 2012-04-25
JP2011523859A (ja) 2011-08-25
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EP3473643A1 (en) 2019-04-24
IL209854A (en) 2013-09-30

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