CN116003529A - 多肽及其在修复黏膜损伤或皮肤损伤上的应用 - Google Patents
多肽及其在修复黏膜损伤或皮肤损伤上的应用 Download PDFInfo
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Abstract
本发明涉及多肽及其在修复黏膜损伤或皮肤损伤上的应用，本发明的多肽与已知多肽无同源性，而且能够在体内和体外均稳定存在，具有调控干细胞增殖和分化修复黏膜损伤或皮肤损伤的效果；以及涉及所述新型多肽通过调控干细胞增殖和分化修复黏膜损伤或皮肤损伤的用途，以及用于预防、减轻或治疗胃肠疾病的用途。
Description
技术领域
本发明涉及多肽及其在修复黏膜损伤或皮肤损伤上的应用，本发明的多肽与已知多肽无同源性，而且能够在体内和体外均稳定存在，具有调控干细胞增殖和分化，修复黏膜损伤或皮肤损伤的效果，以及涉及所述新型多肽通过调控干细胞增殖和分化修复黏膜损伤或皮肤损伤的用途，以及用于预防、减轻或治疗胃肠疾病的用途。
背景技术
皮肤损伤和/或黏膜损伤是很多疾病的共同病理特征。皮肤损伤是指正常皮肤(组织)在外界致伤因子如外科手术、外力、热、电流、化学物质、低温以及机体内在因素如局部血液供应障碍等作用下所导致的损害。皮肤损伤常伴有皮肤完整性的破坏以及一定量正常组织的丢失，同时，皮肤的正常功能受损。也称为伤口或者创伤。目前有包括碱性成纤维生长因子、表皮生长因子、血小板生长因子、粒-巨噬细胞集落刺激因子及生长激素等蛋白质/多肽药物具有明显的修复创面、护肤、抗皱和防衰老作用，但这些蛋白质/多肽药物的氨基酸序列较长导致制备成本高、稳定性较差等缺点，因而其应用受到了一定的限制。
人体黏膜是指呼吸系统、消化系统、生殖泌尿系统等腔道或囊状肌性器官的内层，是仅次于皮肤的人体第二大屏障，包括口腔、咽、气管、食道、胃、肠道、阴道、膀胱等，这些器官的管壁或囊壁均有共同的分层规律，又具有与其功能相适应的特点，其胚胎起源、组织结构、病理过程、临床表现、愈后等均有共同特点。
慢性胃炎是一种胃黏膜慢性炎症，是消化内科的常见病和多发病，临床上将不同原因引起的胃黏膜慢性炎症(即在病理上表现为单核细胞和淋巴细胞浸润)和(或)腺体萎缩性病变称为慢性胃炎。以胃黏膜上皮和腺体萎缩为特征的慢性萎缩性胃炎(chronicatrophic gastrifis,CAG)，其起病隐匿、病程长、症状无特异性、难以治愈，在慢性胃炎中占11％～31％，好发于中老年人群，发病和年龄有一定的关联但与性别没有关系，发病缓慢且病势缠绵，迁延难愈，治疗棘手。慢性萎缩性胃炎是胃癌发生发展重要阶段被视为胃癌前病变，1978年世界卫生组织WHO)已将CAG列为癌前状态，其常伴假幽门腺化生和肠上皮化生，或不典型增生阶段等癌前病变。尤其是伴有弥漫的肠上皮化生或不典型增生者，癌变可能性更大，业界大多数专业人士都赞同通过慢性浅表性胃炎、萎缩性胃炎、肠上皮化生、异型增生、肠型胃癌这样的发展模式。故早期准确的诊断和治疗对慢性萎缩性胃炎患者有着重要的意义。目前现代医学治疗本病主要以改善症状、手术介入为主，在腺体萎缩、肠化生方面尚无良策。CAG为慢性胃炎转变为胃癌的重要阶段，积极治疗CAG对预防其癌变、降低胃癌发病率有着深远意义。寻求萎缩性胃炎的有效治疗方法，是更好地开展胃癌预防的重要措施之一。
黏膜组织的损伤临床上会导致慢性胃炎和消化道溃疡等胃肠道疾病。黏膜上皮的修复有修复(restitution)和再生(regeneration或renewal)两种不同的机制(Cur.Med.Chem.,2008,15,3133-3144)：修复或恢复一般在损伤后几分钟内就开始，通过细胞迁移快速修复浅表病变；再生是通过干细胞和祖细胞的分化和增殖持续再生，持续数天至数月。
因此，需要一种体内外稳定、能够治疗皮肤和/或黏膜损伤，特别是胃肠道黏膜损伤的肽类物质。
发明内容
为了克服现有技术的不足和缺陷，本发明的目的在于提供一类新型多肽。
第一方面，本发明提供式(I)的化合物或其生理学上相容的盐，其中所述式(I)的化合物如下：
H-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Ala-Ala-Glu-Pro-Val-Pro-Leu
-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21-Xaa22-
Xaa23-Xaa24-Xaa25-OH(I)
其中
Xaa1为Ala或缺失；
Xaa2为Ala或缺失；
Xaa3为Ala、Arg、Glu或缺失；
Xaa4为Pro、Lys、Ala或缺失；
Xaa5为Glu、Val、Asp、Gln、Lys、Ala、Pro或缺失；
Xaa6为Pro、Gln、Lys、Val、Ala或缺失；
Xaa7为Ala、Leu、Gly、Lys、Gln、Glu、Val、Asp、Pro、Tyr或缺失；
Xaa8为Pro、Leu、Lys、Glu、Gly、Ile、Leu、Val、Gly、Ala或缺失；
Xaa9-Xaa10-Xaa11为Val-Lys-Gln、Ala-Gly-Leu、Ala-Ala-Val、Val-Pro-Ala；
Xaa12为Asp、Ala、Gln、Lys、Glu、Ala或缺失；
Xaa13为Ala、Leu、Gly、Lys、Gln、Asp、Cys、Glu或缺失；
Xaa14为Ala、Leu、Val、Pro、Gly、Glu或缺失；
Xaa15-Xaa16为Gly-Leu、Pro-Leu、Val-Pro、Pro-Leu、Ala-Glu、Ala-Ala、Val-Pro、Cys-Gly或缺失；
Xaa17为Asp、Leu、Pro、Glu或缺失；
Xaa18-Xaa19-Xaa20-Xaa21为Val-Lys-Gln-Asp、Pro-Val-Pro-Leu、Val-Pro-Leu-Val或缺失；Xaa22-Xaa23-Xaa24为Lys-Gln-Asp、Val-Lys-Gln或缺失；
以及Xaa25为Asp或缺失；
化合物至少为10肽。
在一实施方案中，化合物选自：
化合物1：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物2：Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物3：Gly-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物4：Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物5：Gln-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物6：Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物7：Glu-Pro-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物8：Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物9：Val-Pro-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物10：Asp-Gln-Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物11：Gln-Lys-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物12：Lys-Val-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物13：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Ala、
化合物14：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu、
化合物15：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gly、
化合物16：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Lys、
化合物17：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gln、
化合物18：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Asp、
化合物19：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Ala、
化合物20：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Gln、
化合物21：Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物22：Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物23：Glu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物24：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Lys、化合物25：Ala-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物26：Ala-Ile-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物27：Ala-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物28：Ala-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物29：Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物30：Leu-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物31：Lys-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物32：Glu-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物33：Lys-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物34：Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物35：Val-Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物36：Ala-Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物37：Val-Pro-Leu-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物38：Pro-Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物39：Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物40：Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物41：
Ala-Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物42：
Ala-Ala-Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物43：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Ala-Gly-Leu-Asp、化合物44：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Ala-Ala-Val-Asp、化合物45：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、化合物46：Asp-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物47：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Ala、化合物48：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Ala-Leu、化合物49：Ala-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物50：Leu-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物51：Lys-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物52：Glu-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物53：Lys-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物54：Glu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物55：Val-Pro-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物56：Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu、
化合物57：Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物58：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu、
化合物59：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Ala-Gly-Leu-Asp、化合物60：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Val-Pro-Leu、
化合物61：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Pro-Val-Pro-Leu、化合物62：
Val-Pro-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Val-Pro-Leu、
化合物63：
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物64：
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物65：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Leu、
化合物66：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Ala、
化合物67：Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物68：Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物69：Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln、
化合物70：Arg-Lys-Asp-Val-Tyr-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物71：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Cys-Gly、
化合物72：
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物73：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Glu-Cys-Gly、
化合物74：Ala-Ala-Ala-Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物75：Ala-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物76：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp。
为方便起见，在本申请中描述本发明的化合物时，省略左侧的H和右侧的OH。
在一实施方案中，Xaa9-Xaa10-Xaa11为Val-Lys-Gln。
在一实施方案中，Xaa12为Asp。
在一实施方案中，Xaa12为Glu。
在一实施方案中，Xaa8为Pro、Val或Leu。
在一实施方案中，化合物选自：
化合物1：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物34：Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物36：Ala-Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物39：Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物37：Val-Pro-Leu-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp或
化合物38：Pro-Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp。
第二方面，本发明提供一种修复黏膜损伤的方法，该方法包括对受试者给予本发明的化合物或其生理学上相容的盐或使黏膜损伤与本发明的化合物或其生理学上相容的盐接触。
在一实施方案中，修复是通过调控干细胞增殖和分化进行的。
在一实施方案中，黏膜损伤是消化系统、呼吸系统等腔道内黏膜损伤。
消化系统黏膜损伤与口腔、食道、胃肠疾病相关，口腔疾病包括口腔溃疡、口腔炎、牙龈炎、牙周炎等；食道疾病包括食管炎、食管溃疡等；胃肠疾病包括慢性胃炎、慢性萎缩性胃炎、急性胃炎、胃十二指肠溃疡、功能性胃肠道疾病、消化不良、癌前病变、消化系统肿瘤、胃肠道出血、胃食管返流疾病、急慢性肠炎、溃疡性结肠炎、克罗恩病和放化疗引起的黏膜损伤，但不限于此。
在优选的实施方案中，消化道黏膜包括胃黏膜和肠黏膜。
在优选的实施方案中，慢性胃炎包括慢性萎缩性胃炎。
在优选的实施方案中，黏膜损伤是由刺激性物质或药物、应激状态引起的胃黏膜损伤。其中，刺激性物质如盐酸、乙醇或酒精等，药物例如非类固醇类抗炎药阿司匹林或吲哚美辛，致癌剂或抑酸剂等。
本发明提供一种预防、减轻或治疗消化道疾病或消除炎症水肿的方法，该方法包括对受试者给予本发明的化合物或其生理学上相容的盐。
消化道疾病包括口腔、食道、胃肠疾病相关，口腔疾病包括口腔溃疡、口腔炎、牙龈炎、牙周炎等；食道疾病包括食管炎、食管溃疡等；胃肠疾病包括慢性胃炎、慢性萎缩性胃炎、急性胃炎、胃十二指肠溃疡、功能性胃肠道疾病、消化不良、癌前病变、消化系统肿瘤、胃肠道出血、胃食管返流疾病、急慢性肠炎、溃疡性结肠炎、克罗恩病和放化疗引起的黏膜损伤；但不限于此。
在一实施方案中，消化道疾病的预防、减轻或治疗是通过调控干细胞增殖和分化进行的。方法通过本发明的化合物或其生理学上相容的盐对胃黏膜或肠黏膜等消化道黏膜起到保护作用或修复胃黏膜或肠黏膜等消化道黏膜的损伤，从而起到预防、减轻或治疗胃肠疾病的作用。
本发明提供一种修复黏膜或皮肤创面的方法，该方法包括对受试者给予本发明的化合物或其生理学上相容的盐。在一实施方案中，黏膜或皮肤创面的修复包括调控干细胞增殖和分化。
在上述本发明的方法中，本发明的化合物或其生理学上相容的盐是通过口服、注射、皮下等方式给药的。
第三方面，本发明提供一种修复皮肤损伤的方法，该方法包括使皮肤损伤与本发明的化合物或其生理学上相容的盐接触。
在优选的实施方案中，皮肤损伤与表皮炎症、机械及手术创面、烧伤及烫伤、溃疡、瘘管、褥疮、放化疗引起的皮肤损伤相关，但不限于此。
在一实施方案中，皮肤损伤是指正常皮肤在外界致伤因子如外科手术、外力、热、电流、化学物质、低温以及机体内在因素如局部血液供应障碍等作用下所导致的损害。
在一实施方案中，皮肤损伤常伴有皮肤完整性的破坏以及一定量正常组织的丢失。
在另一实施方案中，皮肤损伤包括皮肤的正常功能受损。
在一实施方案中，皮肤损伤的恢复是通过调控干细胞增殖和分化进行的。
本发明提供一种促进HaCAT细胞增殖的方法，该方法包括使细胞与本发明的化合物或其生理学上相容的盐接触。
第四方面，本发明提供一种使损伤的血管再生的方法，该方法包括使损伤的血管与本发明的化合物或其生理学上相容的盐接触。
在优选的实施方案中，损伤的血管包括消化道黏膜损伤和皮肤损伤导致的血管损伤。
第五方面，本发明提供一种药物、食品、保健品或化妆品、日用品组合物，该组合物包括本至少一种发明的化合物或其生理学上相容的盐以及生理学上可接受的载体。
在一实施方案中，生理学上可接受的载体包括药学上可接受的载体或化妆品可接受的载体。药物食品、保健品或化妆品、日用品组合物可以按照制剂学或化妆品常规技术制备，包括将作为活性成分的本发明的化合物与载体混合，按照常规技术制成所需要的剂型。可以根据需要，将本发明的组合物配制成口服施用制剂、黏膜施用制剂、注射制剂、吸入制剂和外用制剂。
本发明的多肽与已知多肽无同源性，便于人工多肽合成以获得高纯度多肽，与表皮生长因子多肽相比本发明的多肽至多仅由25个氨基酸残基组成在体内稳定，而且本发明的多肽能促进干细胞增殖分化，特别是能促进胃类器官的增殖和分化，参与并调控胃上皮干细胞的增殖和分化，从而可对胃肠干细胞，表皮干细胞损伤进行修复，具有显著的减轻诸如慢性胃炎及消化道溃疡的胃肠疾病病理发展、消除炎症水肿、促进消化道黏膜损伤修复和皮肤损伤修复、缩短创面愈合时间、调解免疫功能等作用。此外，本发明的多肽用于体表皮肤创面时即使经碘制剂或双氧水消毒之后也能够起作用或者在人工胃液、人工肠液等中也能稳定存在，而表皮生长因子用于体表皮肤时，经碘制剂或双氧水消毒之后结构会破坏，不能发挥作用。
附图说明
图1示出了多肽固相合成步骤的示意图；
图2示出了化合物34对小鼠胃类器官活率的影响；
图3示出了化合物36对小鼠胃类器官活率的影响；
图4示出了化合物38对小鼠胃类器官活率的影响；
图5示出了化合物39对小鼠胃类器官活率的影响。
具体实施方式
术语“生理学上相容的盐”是指生理学上相容的(即药理学上可接受的)并且对将被施用本发明化合物的个体基本上无毒的盐形式。本发明化合物的生理学上相容的盐包括由适宜的、无毒的有机或无机酸或无机碱形成的常规的和化学计量的酸加成盐或碱加成盐。
术语“受试者”是指动物，优选为哺乳动物，最优选为人。具体地讲，术语“受试者”涉及具有皮肤损伤和/或黏膜损伤的哺乳动物或人。本领域技术人员应理解，本发明的皮肤损伤和/或黏膜损伤的修复可出于美容目的(即非治疗性目的)和治疗性目的施用。为此，本申请的术语“皮肤损伤”还包括出于美容目的修复的皮肤损伤例如，皱纹(例如紫外线照射导致的皱纹)、皮肤纹、裂缝、肿块、大毛孔(例如与附件结构如汗腺管、皮脂腺或毛囊相关的)，或不平或粗糙，皮肤失去弹性(功能性皮肤弹性蛋白丧失和/或失活)、下垂(包括眼部和下颌浮肿)、皮肤硬度丧失、皮肤紧实度丧失、皮肤变形后的回复能力丧失、变色(包括黑眼圈)、斑疱、肤色灰黄、色素过量皮肤区域例如老年斑和雀斑、角质物、异常的分化、过度角质化、弹性组织变性、胶原蛋白的破坏，以及皮肤角质，真皮，表皮层，皮肤血管系统(例如毛细血管扩张或多叉血管)，以及皮下组织，特别是靠近皮肤的皮下组织中的其它组织变化。
以下是结合具体试验对本发明的说明，并不是对本发明保护范围的限制。
表1.溶剂及试剂等的英文、缩写与相应的中文名称
| 英文、缩写 | 中文名称 |
| 2-Chlorotrityl Chloride Resin | 2-氯三苯甲基氯树脂 |
| DMF | N,N-二甲基甲酰胺 |
| DCM | 二氯甲烷 |
| PIP | 哌啶 |
| HOBt | 1-羟基苯并三唑 |
| DIPEA | N,N-二异丙基乙胺 |
| Methanol | 甲醇 |
| tert-Butyl methyl ether | 甲基叔丁基醚 |
| TFA | 三氟乙酸 |
| TIS | 三异丙基硅烷 |
| DIC | N,N'-二异丙基碳二亚胺 |
| Ethanol | 乙醇 |
| Aa | 氨基酸 |
实施例1：多肽的化学合成
多肽化合物的合成采用常规固相合成方法，经过树脂溶胀、氨基酸取代、脱保护、洗涤，以及氨基酸活化、缩合、洗涤、脱保护的多个循环过程，最后裂解和侧链脱保护。
多肽固相合成步骤示意图参见图1。图1中，Cl-2-Cl-Resin表示2-氯三苯甲基氯树脂(2-Chlorotrityl Chloride Resin)；Fmoc-Aa(n)等表示9-芴基甲氧基羰基的氨基酸；TIPS为三异丙基硅烷。
以下以化合物14(Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu)为例，采用CS BIO公司的型号为CS 136M的多肽自动合成仪，示出化合物14的合成和纯化的方法。
该方法包括步骤1、全保护肽树脂的制备；2、切割、脱保护；3、纯化(换盐)冻干。
步骤1、全保护肽树脂的制备
(1)Fmoc-Leu-Resin树脂的制备：称取2.67g的2-Chlorotrityl Chloride Resin(SD＝0.75mmol/g)，加入自动多肽合成仪CS 136M的合成管中，利用多肽合成仪设定好的程序，进行第一个氨基酸的取代反应和脱除保护基Fmoc。具体反应过程如下：将树脂用DCM溶胀20分钟后排干。将Fmoc-Leu-OH(3eq，6mmol)溶于DMF(40mL)中，然后加入DIPEA(7eq，14mmol)。将Fmoc-Leu-OH/DIPEA的DMF混合溶液加入含有树脂的反应瓶中反应1小时，排干。加入40mL的20％ MeOH/DMF反应30分钟进行封端，排干后用DMF洗3次，然后用20％ PIP/DMF(v/v)脱除保护基Fmoc后，再用DMF溶液洗5次。
(2)全保护肽树脂的制备：将循环水浴温度调节至35℃，利用多肽合成仪设定好的偶联程序，按照多肽序列从第(n-1)个氨基酸开始逐一偶联氨基酸。具体反应过程如下：在活化瓶中将Fmoc-Asp(OtBu)-OH(3eq，6mmol)和HOBt(3eq，6mmol)溶于DMF(40mL)，然后加入DIC(4eq，8mmol)活化氨基酸。将Fmoc-Asp(OtBu)-OH/HOBt/DIC的DMF混合溶液加入上步的氨基酸树脂在反应瓶中偶联，反应1小时后，排出溶剂，固体树脂用DMF溶液洗3次，然后用20％ PIP/DMF(v/v)脱除保护基Fmoc后用DMF溶液洗5次。重复上述步骤，直至整个氨基酸序列偶联完成。
步骤2、切割
(1)将多肽合成仪中的树脂转移至带有筛板的手动合成管中，并用DCM洗5次。在合成管中加入200mL的切割剂(TFA:TIS:H2O＝95:2.5:2.5，v/v)，氮气(N2)鼓泡反应1.5～3小时。
(2)切割反应完成后，将切割剂抽滤至250mL的圆底烧瓶中。真空浓缩至原切割剂体积的四分之一后，加入10倍现有体积的甲基叔丁基醚，沉降得白色固体。将所得混合溶剂过滤，并用20mL的甲基叔丁基醚分别清洗3次后，将所得粗肽产品置于真空干燥箱中除去多余溶剂至粗肽为粉末状。得到粗肽1.70g，粗产率61.7％。
步骤3、纯化、换盐和冻干
色谱参数
色谱柱：YMC-Actus Triart C18 30*250mm(L.D S-5um,12nm)
洗脱液A1：0.1M乙酸
洗脱液A2：0.025M乙酸—0.1M乙酸铵
洗脱液B：乙腈
流速：25mL/min
紫外检测波长：220nm
操作步骤
a)95％ A1+5％ B平衡色谱柱
b)进样，0.464g样品用8mL纯化水溶解并经孔径0.45um滤器过滤。
c)95％ A2+5％ B平衡色谱柱
d)A1和B梯度洗脱，梯度如下
| 时间min | A1％(0.1M乙酸) | 乙腈 |
| 0 | 95 | 5 |
| 15 | 70 | 30 |
| 17 | 5 | 95 |
| 20 | 5 | 95 |
e)收集目的肽洗脱液
f)旋蒸浓缩:水浴温度40℃
g)冷冻干燥
纯化粗品0.464g，得纯品0.371g，纯度：100％，收率：79.95％。
以与合成化合物14类似的方式，合成其他化合物。结果参见表2和说明书其他部分。
表2合成的化合物
注释：双电荷峰表示目标分子结合2个质子，三电荷峰表示目标分子结合3个质子；N/A代表粗品没有称量，未计算纯化收率。
化合物1:Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp
高分辨质谱(TOF-HRMS)，分子式：C60H99N15O19；m/z：667.86710([M+2H]2+)，1334.72627([M+H]+).
化合物2:Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp
高分辨质谱(TOF-HRMS)，分子式：C63H105N15O19；m/z：688.89313([M+2H]2+).1H NMR(600MHz,D2O)δ4.59–4.53(m,1H),4.45–4.36(m,3H),4.35–4.29(m,3H),4.29–4.18(m,5H),4.04(d,J＝8.2Hz,1H),3.84–3.59(m,4H),3.57–3.50(m,1H),2.94(t,J＝7.4Hz,2H),2.74–2.61(m,2H),2.45–1.47(m,31H),1.42–1.35(m,2H),1.35–1.28(m,6H),0.97–0.81(m,24H).
化合物3:Gly-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.56–4.52(m,1H),4.41–4.31(m,3H),4.31–4.13(m,7H),3.99(d,J＝8.2Hz,1H),3.88(s,2H),3.85–3.73(m,1H),3.73–3.66(m,1H),3.62–3.54(m,2H),3.54–3.42(m,2H),2.89(t,J＝7.4Hz,2H),2.76–2.62(m,2H),2.39–2.13(m,7H),2.08–
1.42(m,29H,AcOH),1.39–1.30(m,2H),1.30–1.24(m,6H),0.92–0.76(m,18H).
化合物4:Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp
高分辨质谱(TOF-HRMS)，分子式：C63H106N16O19；m/z：696.40099([M+2H]2+，1391.78631([M+H]+).
1H NMR(600MHz,D2O)δ4.53–4.48(m,1H),4.43(t,J＝7.8Hz,1H),4.40–4.23(m,9H),4.23–4.17(m,1H),4.04(d,J＝8.2Hz,1H),3.84–3.59(m,4H),3.58–3.51(m,1H),2.99–2.92(m,4H),2.63–2.57(m,1H),2.55–2.48(m,1H),2.34–1.36(m,36H),1.35(d,J＝7.2Hz,3H),1.32–1.27(m,3H),0.98–0.81(m,18H).
化合物5:Gln-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C62H102N16O20；m/z：696.38223([M+2H]2+).1H NMR(600MHz,D2O)δ4.49(dd,J＝9.4,4.8Hz,1H),4.38(dd,J＝8.2,6.7Hz,1H),4.36–4.26(m,6H),4.25–4.14(m,4H),3.99(d,J＝8.2Hz,1H),3.81–3.47(m,5H),2.90(t,J＝7.3Hz,2H),2.64–2.58(m,1H),2.57–2.50(m,1H),2.45–2.38(m,2H),2.29–2.13(m,7H),2.12–1.69(m,18H,AcOH),1.68–1.43(m,6H),1.38–1.31(m,2H),1.31–1.24(m,6H),0.91–0.77(m,18H).
化合物6:Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C62H101N15O21；m/z：696.87068([M+2H]2+)，1392.73264([M+H]+).
1H NMR(600MHz,D2O)δ4.56(dd,J＝9.5,4.8Hz,1H),4.43–4.14(m,10H),3.99(d,J＝8.2Hz,1H),3.83–3.74(m,1H),3.73–3.45(m,4H),2.89(t,J＝7.5Hz,2H),2.76–2.65(m,2H),2.44–2.21(m,7H),2.20–1.43(m,31H,AcOH),1.39–1.30(m,2H),1.30–1.24(m,6H),0.92–0.76(m,18H).
化合物7:Glu-Pro-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.62–4.56(m,2H),4.50–4.46(m,1H),4.45–4.41(m,1H),4.41–4.36(m,1H),4.35–4.29(m,5H),4.28–4.13(m,4H),4.03(d,J＝8.2Hz,1H),3.85–3.78(m,2H),3.77–3.71(m,1H),3.70–3.54(m,4H),2.94(t,J＝7.5Hz,2H),2.80–2.68(m,2H),2.45(t,J＝7.2Hz,2H),2.43–2.35(m,2H),2.31(t,J＝7.6Hz,2H),2.28–1.73(m,31H,AcOH),1.72–1.47(m,6H),1.43–1.34(m,2H),1.34–1.27(m,6H),0.97–0.80(m,24H).化合物8:Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)高分辨质谱(TOF-HRMS)，分子式：C73H121N17O21；m/z：786.95519([M+2H]2+).1H NMR(600MHz,D2O)δ4.56–4.48(m,2H),4.42–4.31(m,3H),4.31–4.25(m,4H),4.24–4.14(m,4H),4.08(d,J＝5.5Hz,1H),3.99(d,J＝8.3Hz,1H),3.79–3.35(m,7H),2.90(t,J＝7.4Hz,2H),2.72–2.58(m,2H),2.38–2.23(m,4H),2.23–2.12(m,4H),2.08–1.43(m,33H,AcOH),1.38–1.29(m,2H),1.29–1.24(m,6H),1.01(d,J＝7.0Hz,3H),0.92–0.78(m,27H).
化合物9:Val-Pro-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C72H119N17O21；m/z：779.94770([M+2H]2+).1H NMR(600MHz,D2O)δ4.60–4.54(m,2H),4.49–4.44(m,1H),4.43–4.36(m,2H),4.36–4.29(m,4H),4.29–4.19(m,4H),4.12(d,J＝5.5Hz,1H),4.03(d,J＝8.2Hz,1H),3.84–3.79(m,1H),3.77–3.67(m,2H),3.66–3.51(m,4H),2.94(t,J＝7.4Hz,2H),2.76–2.64(m,2H),2.40–2.17(m,8H),2.12–1.73(m,26H,AcOH),1.72–1.48(m,5H),1.43–1.34(m,2H),1.34–1.27(m,6H),1.05(d,J＝7.0Hz,3H),0.96–0.82(m,27H).
化合物10:Asp-Gln-Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.61–4.50(m,3H),4.42–4.29(m,7H),4.28–4.17(m,5H),4.03(d,J＝8.2Hz,1H),3.83–3.71(m,2H),3.66–3.54(m,2H),2.94(q,J＝7.0Hz,4H),2.80–2.62(m,4H),2.40–2.16(m,9H),2.11–1.72(m,25H,AcOH),1.70–1.47(m,9H),1.46–1.33(m,4H),1.33–1.26(m,6H),0.96–0.80(m,18H).
化合物11:Gln-Lys-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.55(dd,J＝9.5,4.5Hz,2H),4.40–4.19(m,11H),4.06–4.00(m,2H),3.83–3.79(m,1H),3.74(q,J＝7.4Hz,1H),3.66–3.60(m,2H),2.93(q,J＝8.6,8.1Hz,4H),2.71–2.58(m,2H),2.39–2.16(m,8H),2.12–1.48(m,35H,AcOH),1.44–1.33(m,4H),1.33–1.27(m,6H),0.97–0.81(m,24H).
化合物12:Lys-Val-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.62–4.54(m,3H),4.47–4.17(m,10H),4.11–3.97(m,3H),3.84–3.70(m,2H),3.67–3.58(m,2H),2.93(td,J＝7.6,4.8Hz,4H),2.74–2.62(m,2H),2.39–2.28(m,4H),2.26–2.18(m,2H),2.11–1.47(m,40H,AcOH),1.42–1.33(m,4H),1.33–1.26(m,6H),0.97–0.81(m,30H).
化合物13:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Ala(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dt,J＝8.5,4.6Hz,2H),4.38–4.31(m,1H),4.31–4.13(m,8H),4.06(q,J＝7.2Hz,1H),3.99(d,J＝8.1Hz,1H),3.77(q,J＝6.9,5.6Hz,1H),3.73–3.65(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.5Hz,2H),2.75–2.69(m,1H),2.64–2.56(m,1H),2.40–2.24(m,5H),2.22–2.12(m,2H),2.06–1.83(m,17H,AcOH),1.82–1.43(m,10H),1.39–1.30(m,2H),1.30–1.23(m,9H),0.92–0.77(m,18H).
化合物14:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C63H105N15O19；m/z：688.89126([M+2H]2+)，1376.77455([M+H]+).
1H NMR(600MHz,D2O)δ4.61–4.52(m,2H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.27(m,3H),4.26–4.16(m,5H),4.15–4.10(m,1H),3.99(d,J＝8.1Hz,1H),3.77(q,J＝7.0,5.8Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.5Hz,2H),2.77–2.70(m,1H),2.63–2.56(m,1H),2.40–2.22(m,5H),2.21–2.12(m,2H),2.03–1.68(m,23H,AcOH),1.67–1.42(m,9H),1.42–1.30(m,2H),1.30–1.23(m,6H),0.93–0.74(m,24H).
化合物15:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gly(醋酸盐)
1H NMR(600MHz,D2O)δ4.61(dd,J＝8.1,5.3Hz,1H),4.55(dd,J＝9.5,4.7Hz,1H),4.34(dd,J＝8.4,5.9Hz,1H),4.29(dd,J＝8.3,5.9Hz,3H),4.26–4.17(m,5H),3.99(d,J＝8.1Hz,1H),3.82–3.73(m,1H),3.72–3.67(m,3H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.5Hz,2H),2.77–2.70(m,1H),2.66–2.60(m,1H),2.40–2.29(m,3H),2.26(t,J＝7.6Hz,2H),2.22–2.12(m,2H),2.06–1.83(m,21H,AcOH),1.82–1.67(m,4H),1.67–1.42(m,6H),1.39–1.30(m,2H),1.30–1.24(m,6H),0.94–0.73(m,18H).
化合物16:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Lys(醋酸盐)
1H NMR(600MHz,D2O)δ4.56–4.50(m,2H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.16(m,8H),4.07(dd,J＝7.9,5.1Hz,1H),3.99(d,J＝8.2Hz,1H),3.77(q,J＝6.6,6.0Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.92–2.86(m,4H),2.70–2.63(m,1H),2.60–2.53(m,1H),2.40–2.24(m,5H),2.23–2.12(m,2H),2.06–1.84(m,21H,AcOH),1.82–1.67(m,5H),1.66–1.50(m,8H),1.50–1.42(m,1H),1.37–1.22(m,10H),0.93–0.77(m,18H).
化合物17:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gln(醋酸盐)
1H NMR(600MHz,D2O)δ4.58–4.52(m,2H),4.34(dd,J＝8.3,5.8Hz,1H),4.31–4.14(m,8H),4.10(dd,J＝8.6,4.9Hz,1H),3.99(d,J＝8.1Hz,1H),3.82–3.74(m,1H),3.73–3.65(m,1H),3.64–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.6Hz,2H),2.77–2.70(m,1H),2.66–2.59(m,1H),2.40–2.23(m,5H),2.23–2.13(m,4H),2.05–1.81(m,20H,AcOH),1.80–1.67(m,4H),1.66–1.42(m,6H),1.38–1.24(m,8H),0.92–0.77(m,18H).
化合物18:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.60(dd,J＝8.1,5.2Hz,1H),4.58–4.54(m,1H),4.42(t,J＝5.9Hz,1H),4.34(dd,J＝8.4,5.9Hz,1H),4.31–4.13(m,8H),3.99(d,J＝8.1Hz,1H),3.80–3.73(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.90(t,J＝7.5Hz,2H),2.80–2.73(m,1H),2.73–2.66(m,2H),2.66–2.59(m,1H),2.41–2.29(m,3H),2.26(t,J＝7.6Hz,2H),2.20–2.13(m,2H),2.05–1.83(m,20H,AcOH),1.82–1.67(m,4H),1.67–1.42(m,6H),1.37–1.24(m,8H),0.92–0.76(m,18H).
化合物19:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Ala(醋酸盐)
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.5,4.7Hz,1H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.27(m,3H),4.27–4.18(m,5H),4.07–4.01(m,1H),3.99(d,J＝8.2Hz,1H),3.80–3.74(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.6Hz,2H),2.40–2.24(m,5H),2.22–2.12(m,2H),2.06–1.83(m,19H,AcOH),1.82–1.42(m,9H),1.36–1.22(m,11H),0.92–0.77(m,18H).
化合物20:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Gln(醋酸盐)
1H NMR(600MHz,D2O)δ4.52(dd,J＝9.5,4.7Hz,1H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.26(m,3H),4.25–4.14(m,5H),4.07(dd,J＝8.4,4.9Hz,1H),3.99(d,J＝8.2Hz,1H),3.81–3.74(m,1H),3.74–3.67(m,1H),3.64–3.54(m,2H),3.37-3.24(m,2H),2.89(t,J＝7.6Hz,2H),2.40–2.23(m,5H),2.23–2.12(m,4H),2.07–1.43(m,28H,AcOH),1.38–1.24(m,8H),0.93–0.77(m,18H).
化合物21:Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.38(dd,J＝7.0,5.1Hz,1H),4.34(dd,J＝8.3,5.9Hz,1H),4.31–4.14(m,7H),3.99(d,J＝8.2Hz,1H),3.90(t,J＝7.1Hz,1H),3.80–3.66(m,2H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.74–2.62(m,2H),2.39–2.23(m,4H),2.22–2.12(m,2H),2.08–1.43(m,28H,AcOH),1.37–1.23(m,8H),0.93–0.76(m,24H).
化合物22:Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C58H99N15O18；m/z：647.87059([M+2H]2+)，1294.73375([M+H]+).
1H NMR(600MHz,D2O)δ4.51(dd,J＝9.7,4.6Hz,1H),4.38–4.31(m,2H),4.31–4.10(m,7H),3.99(d,J＝8.3Hz,1H),3.90(t,J＝6.6Hz,1H),3.80–3.73(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.94–2.87(m,4H),2.70–2.58(m,2H),2.31–2.22(m,4H),2.22–2.12(m,2H),2.08–2.01(m,1H),2.00–1.68(m,22H,AcOH),1.66–1.24(m,18H),0.91–0.76(m,18H).
化合物23:Glu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.56(dd,J＝9.5,4.8Hz,1H),4.40(dd,J＝6.8,5.2Hz,1H),4.37–4.09(m,8H),4.03–3.92(m,2H),3.76(q,J＝6.7,5.6Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.76–2.65(m,2H),2.42–2.31(m,4H),2.27(t,J＝7.6Hz,2H),2.21–2.12(m,2H),2.09–1.82(m,16H,AcOH),1.82–1.42(m,10H),1.38–1.24(m,8H),0.92–0.76(m,18H).
化合物24:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Lys(醋酸盐)
1H NMR(600MHz,D2O)δ4.53–4.48(m,1H),4.33(dd,J＝8.4,5.8Hz,1H),4.31–4.27(m,3H),4.27–4.16(m,5H),4.03(dd,J＝7.9,5.4Hz,1H),3.98(d,J＝8.2Hz,1H),3.83–3.74(m,1H),3.74–3.67(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.6Hz,4H),2.40–2.31(m,1H),2.31–2.22(m,4H),2.21–2.12(m,2H),2.07–1.84(m,22H,AcOH),1.82–1.68(m,5H),1.66–1.43(m,9H),1.37–1.24(m,10H),0.93–0.76(m,18H).
化合物25:Ala-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.5,4.8Hz,1H),4.37(dd,J＝7.1,5.1Hz,1H),4.34(dd,J＝8.3,5.9Hz,1H),4.32–4.24(m,3H),4.24–4.16(m,4H),4.04(q,J＝7.1Hz,1H),3.99(d,J＝8.2Hz,1H),3.90(s,2H),3.76(q,J＝6.9,5.5Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.73–2.58(m,2H),2.37–2.24(m,4H),2.22–2.12(m,2H),2.08–1.43(m,26H,AcOH),1.39–1.23(m,8H),0.91–0.76(m,18H).
化合物26:Ala-Ile-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.40–4.31(m,2H),4.31–4.24(m,3H),4.24–4.13(m,4H),4.08(d,J＝7.8Hz,1H),4.05–3.97(m,2H),3.80–3.74(m,1H),3.74–3.67(m,1H),3.64–3.53(m,2H),2.89(t,J＝7.4Hz,2H),2.73–2.59(m,2H),2.39–2.22(m,4H),2.22–2.12(m,2H),2.08–1.23(m,36H,AcOH),1.14–1.04(m,1H),0.92–0.75(m,24H).
化合物27:Ala-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.41–4.36(m,1H),4.36–4.31(m,1H),4.31–4.15(m,8H),4.02–3.95(m,2H),3.76(q,J＝7.0,5.5Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.74–2.63(m,2H),2.40–2.23(m,4H),2.22–2.12(m,2H),2.08–1.43(m,30H,AcOH),1.42(d,J＝7.1Hz,3H),1.38–1.23(m,8H),0.92–0.77(m,24H).
化合物28:Ala-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.4,4.8Hz,1H),4.39–4.32(m,2H),4.31–4.25(m,3H),4.24–4.17(m,4H),4.07–3.97(m,3H),3.76(q,J＝7.0,5.4Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.90(t,J＝7.4Hz,2H),2.72–2.59(m,2H),2.38–2.23(m,4H),2.22–2.12(m,2H),2.08–1.43(m,24H,AcOH),1.41(d,J＝7.1Hz,3H),1.38–1.23(m,8H),0.91–0.77(m,24H).
化合物29:Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.38(dd,J＝7.0,5.1Hz,1H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.24(m,3H),4.24–4.17(m,4H),4.03–3.92(m,2H),3.90(d,J＝2.3Hz,2H),3.76(q,J＝6.9,5.7Hz,1H),3.72–3.66(m,1H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.74–2.63(m,2H),2.39–2.23(m,4H),2.22–2.12(m,2H),2.07–1.43(m,29H,AcOH),1.37–1.23(m,8H),0.92–0.76(m,24H).
化合物30:Leu-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.40–4.31(m,2H),4.31–4.14(m,8H),3.99(d,J＝8.2Hz,1H),3.90(t,J＝7.1Hz,1H),3.77(q,J＝6.8,5.7Hz,1H),3.73–3.67(m,1H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.73–2.61(m,2H),2.39–2.23(m,4H),2.21–2.12(m,2H),2.07–1.43(m,27H,AcOH),1.40–1.23(m,11H),0.92–0.76(m,24H).化合物31:Lys-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.49(dd,J＝9.4,4.8Hz,1H),4.36–4.25(m,5H),4.24–4.15(m,4H),4.05(d,J＝7.5Hz,1H),4.03–3.94(m,2H),3.80–3.67(m,2H),3.63–3.54(m,2H),2.90(t,J＝7.8Hz,4H),2.66–2.60(m,1H),2.59–2.53(m,1H),2.30–2.21(m,4H),2.20–2.12(m,2H),2.08–1.68(m,20H,AcOH),1.68–1.42(m,8H),1.40–1.29(m,4H),1.29–1.24(m,6H),0.92–0.77(m,24H).
化合物32:Glu-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.66–4.59(m,1H),4.55(dd,J＝9.5,4.8Hz,1H),4.39(dd,J＝6.9,5.1Hz,1H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.13(m,8H),3.99(d,J＝8.2Hz,1H),3.95(t,J＝6.5Hz,1H),3.84–3.73(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.74–2.63(m,2H),2.41–2.29(m,4H),2.27(t,J＝7.6Hz,2H),2.22–2.12(m,2H),2.10–1.42(m,23H,AcOH),1.40–1.30(m,2H),1.30–1.24(m,9H),0.90–0.77(m,18H).化合物33:Lys-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C61H104N16O19；m/z：683.39009([M+2H]2+)，1365.77275([M+H]+).
1H NMR(600MHz,DMSO-d6)δ8.44(s,1H),8.34–8.22(m,2H),8.12–7.85(m,5H),7.64–7.56(m,2H),7.21(s,1H),6.72(s,1H),4.43–4.04(m,13H),3.67–3.47(m,4H),3.23(s,1H),2.79–2.70(m,4H),2.46–2.35(m,2H),2.13–2.05(m,4H),2.03–1.26(m,35H,AcOH),1.24–1.12(m,9H),0.90–0.76(m,18H).
化合物34:Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C63H104N16O20；m/z：703.38943([M+2H]2+).
1H NMR(600MHz,D2O)δ4.56–4.49(m,2H),4.39–4.24(m,6H),4.24–4.13(m,4H),4.03–3.95(m,2H),3.80–3.74(m,1H),3.74–3.67(m,2H),3.62–3.52(m,3H),2.90(t,J＝7.4Hz,2H),2.71–2.58(m,2H),2.37–2.13(m,7H),2.08–1.68(m,18H,AcOH),1.68–1.43(m,6H),1.41(d,J＝7.1Hz,3H),1.38–1.29(m,2H),1.29–1.21(m,9H),0.93–0.77(m,18H).
化合物35:Val-Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C68H115N17O20；m/z：745.93036([M+2H]2+)，1490.85402([M+H]+).
1H NMR(600MHz,D2O)δ4.59–4.54(m,1H),4.49(dd,J＝9.4,4.9Hz,1H),4.36–4.24(m,6H),4.24–4.19(m,3H),4.19–4.11(m,1H),3.99(d,J＝8.2Hz,1H),3.81–3.73(m,2H),3.73–3.67(m,2H),3.63–3.52(m,3H),2.93–2.84(m,4H),2.67–2.61(m,1H),2.61–2.54(m,1H),2.32–1.43(m,38H,AcOH),1.42–1.34(m,2H),1.33–1.30(m,1H),1.28(d,J＝7.2Hz,3H),1.25(d,J＝7.2Hz,3H),0.94–0.77(m,24H).
化合物36:Ala-Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C65H106N16O22；m/z：732.38868([M+2H]2+)，1463.76896([M+H]+).
1H NMR(600MHz,D2O)δ4.61–4.52(m,2H),4.39(t,J＝6.0Hz,1H),4.34(dd,J＝8.4,5.9Hz,1H),4.31–4.24(m,4H),4.24–4.14(m,4H),4.04–3.96(m,2H),3.80–3.74(m,1H),3.74–3.66(m,2H),3.64–3.54(m,3H),2.89(t,J＝7.4Hz,2H),2.75–2.63(m,2H),2.41–2.29(m,4H),2.27(t,J＝7.6Hz,2H),2.24–2.13(m,3H),2.08–1.68(m,21H,AcOH),1.68–1.42(m,6H),1.41(d,J＝7.2Hz,3H),1.38–1.29(m,2H),1.29–1.22(m,6H),0.92–0.76(m,18H).
化合物37:Val-Pro-Leu-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.57–4.51(m,1H),4.40–4.31(m,3H),4.31–4.14(m,8H),4.08(d,J＝5.4Hz,1H),3.99(dd,J＝8.2,4.2Hz,2H),3.80–3.73(m,1H),3.73–3.63(m,2H),3.62–3.48(m,3H),2.89(t,J＝7.4Hz,2H),2.73–2.62(m,2H),2.40–2.29(m,2H),2.29–2.12(m,6H),2.08–1.82(m,19H,AcOH),1.81–1.68(m,5H),1.67–1.42(m,9H),1.38–1.28(m,2H),1.26(dd,J＝7.2,1.7Hz,6H),1.00(d,J＝6.9Hz,3H),0.92–0.76(m,33H).
化合物38:Pro-Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)高分辨质谱(TOF-HRMS)，分子式：C73H121N17O21；m/z：786.95783([M+2H]2+).
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.41–4.15(m,12H),4.01–3.96(m,1H),3.85–3.75(m,2H),3.73–3.65(m,1H),3.65–3.37(m,3H),3.36–3.25(m,2H),2.89(t,J＝7.4Hz,2H),2.74–2.62(m,2H),2.40–2.24(m,5H),2.24–2.09(m,3H),2.08–1.83(m,23H,AcOH),1.82–1.68(m,5H),1.68–1.42(m,9H),1.39–1.28(m,2H),1.28–1.23(m,6H),0.93–0.77(m,30H).
化合物39:Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)高分辨质谱(TOF-HRMS)，分子式：C78H128N18O22；m/z：835.48070([M+2H]2+).
1H NMR(600MHz,D2O)δ4.55(dd,J＝9.4,4.8Hz,1H),4.49(dd,J＝9.6,5.0Hz,1H),4.40–4.12(m,12H),3.99(d,J＝8.2Hz,1H),3.80–3.73(m,3H),3.72–3.67(m,1H),3.62–3.51(m,3H),3.37–3.25(m,2H),2.89(t,J＝7.4Hz,2H),2.74–2.62(m,2H),2.41–2.29(m,3H),2.27(t,J＝7.6Hz,2H),2.22–2.13(m,3H),2.07–1.67(m,31H,AcOH),1.67–1.44(m,8H),1.38–1.29(m,2H),1.29–1.23(m,6H),0.93–0.77(m,30H).
化合物40:Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C83H135N19O25；m/z：899.99976([M+2H]2+)，1798.99118([M+H]+).
1H NMR(600MHz,D2O)δ4.56(dd,J＝9.3,4.8Hz,1H),4.49(dd,J＝9.7,4.8Hz,1H),4.46–4.38(m,2H),4.38–4.10(m,11H),3.99(d,J＝8.2Hz,1H),3.80–3.45(m,9H),2.89(t,J＝7.4Hz,2H),2.76–2.65(m,2H),2.45–2.30(m,4H),2.27(t,J＝7.6Hz,2H),2.24–1.84(m,30H,AcOH),1.83–1.44(m,15H),1.38–1.29(m,2H),1.27(t,J＝7.2Hz,6H),0.92–0.76(m,30H).
化合物41:Ala-Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.64–4.53(m,2H),4.49(dd,J＝9.7,4.8Hz,1H),4.40(dd,J＝6.9,5.2Hz,1H),4.37–4.32(m,2H),4.32–4.25(m,5H),4.25–4.10(m,4H),4.04–3.95(m,2H),3.80–3.66(m,4H),3.64–3.44(m,5H),2.89(t,J＝7.4Hz,2H),2.76–2.64(m,2H),2.43–2.29(m,4H),2.27(t,J＝7.6Hz,2H),2.22–2.10(m,4H),2.07–1.68(m,32H,AcOH),1.67–1.43(m,9H),1.43–1.39(m,3H),1.37–1.29(m,2H),1.29–1.23(m,6H),0.93–0.76(m,30H).
化合物42:
Ala-Ala-Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)1H NMR(600MHz,D2O)δ4.56(dd,J＝9.7,4.7Hz,2H),4.49(dd,J＝9.7,4.8Hz,1H),4.43–4.38(m,1H),4.37–4.10(m,12H),4.03–3.95(m,2H),3.79–3.66(m,4H),3.64–3.45(m,5H),2.89(t,J＝7.4Hz,2H),2.76–2.65(m,2H),2.43–2.29(m,4H),2.27(t,J＝7.6Hz,2H),2.22–2.11(m,4H),2.06–1.83(m,28H,AcOH),1.83–1.68(m,8H),1.68–1.45(m,9H),1.43(d,J＝7.1Hz,3H),1.39–1.29(m,2H),1.29–1.23(m,9H),0.93–0.76(m,30H).
化合物43:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Ala-Gly-Leu-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.58(dd,J＝9.5,4.7Hz,1H),4.48–4.43(m,1H),4.34(dd,J＝8.4,5.9Hz,1H),4.32–4.27(m,4H),4.27–4.12(m,4H),3.86–3.82(m,2H),3.80–3.73(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.38–3.24(m,2H),2.81–2.74(m,1H),2.74–2.67(m,1H),2.43–2.31(m,3H),2.21–2.12(m,2H),2.03–1.84(m,12H,AcOH),1.83–1.74(m,3H),1.62–1.44(m,6H),1.33–1.24(m,9H),0.92–0.75(m,18H).
化合物44:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Ala-Ala-Val-Asp(醋酸盐)
1H NMR(600MHz,D2O)δ4.56(dd,J＝9.6,4.7Hz,1H),4.43(t,J＝6.1Hz,1H),4.34(dd,J＝8.5,5.9Hz,1H),4.31–4.27(m,3H),4.26–4.11(m,5H),4.04(d,J＝7.2Hz,1H),3.79–3.73(m,1H),3.72–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.78–2.66(m,2H),2.40–2.29(m,3H),2.22–2.12(m,2H),2.05–1.83(m,15H,AcOH),1.82–1.72(m,3H),1.61–1.43(m,3H),1.33–1.23(m,12H),0.93–0.77(m,18H).
化合物45:Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu(醋酸盐)
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.8Hz,1H),4.39–4.31(m,2H),4.31–4.18(m,7H),4.18–4.14(m,1H),4.11(dd,J＝8.6,4.9Hz,1H),3.99(d,J＝8.2Hz,1H),3.80–3.74(m,1H),3.73–3.66(m,1H),3.65–3.54(m,3H),3.53–3.46(m,1H),2.88(t,J＝7.6Hz,2H),2.39–2.13(m,9H),2.06–1.44(m,30H,AcOH),1.42(d,J＝7.0Hz,3H),1.35–1.31(m,1H),1.29(d,J＝7.2Hz,3H),1.25(d,J＝7.1Hz,3H),0.92–0.77(m,18H).
化合物46:Asp-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C61H99N15O21；m/z：689.86298([M+H]+),1378.71780([M+H]+).
1H NMR(600MHz,D2O)δ4.47(dd,J＝9.4,4.7Hz,1H),4.36–4.31(m,2H),4.29–4.21(m,2H),4.21–4.03(m,7H),3.91–3.86(m,1H),3.71–3.64(m,1H),3.63–3.52(m,2H),3.52–3.42(m,3H),2.79(t,J＝7.5Hz,2H),2.73–2.67(m,1H),2.65–2.61(m,2H),2.51–2.43(m,1H),2.35–2.22(m,2H),2.20–2.15(m,2H),2.15–2.10(m,1H),2.10–2.02(m,2H),1.97–1.70(m,20H,AcOH),1.70–1.33(m,10H),1.30–1.19(m,2H),1.19–1.13(m,6H),0.81–0.66(m,18H).
化合物47:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Ala(醋酸盐)
1H NMR(600MHz,D2O)δ4.58–4.52(m,2H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.27(m,3H),4.27–4.15(m,6H),4.08(q,J＝7.3Hz,1H),4.02–3.97(m,1H),3.77(q,J＝6.9,5.9Hz,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.5Hz,2H),2.75–2.68(m,1H),2.63–2.56(m,1H),2.39–2.13(m,6H),2.03–1.82(m,18H,AcOH),1.82–1.68(m,4H),1.67–1.50(m,8H),1.50–1.42(m,1H),1.38–1.31(m,1H),1.30(d,J＝7.3Hz,3H),1.28–1.23(m,6H),0.92–0.75(m,24H).
化合物48:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Ala-Leu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C66H110N16O20；m/z：724.41274([M+2H]2+).
1H NMR(600MHz,D2O)δ4.56–4.49(m,2H),4.34(dd,J＝8.3,5.8Hz,1H),4.32–4.27(m,3H),4.27–4.16(m,6H),4.15–4.10(m,1H),4.01–3.97(m,1H),3.81–3.74(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.5Hz,2H),2.73–2.66(m,1H),2.64–2.57(m,1H),2.40–2.29(m,3H),2.26(t,J＝7.6Hz,2H),2.22–2.12(m,2H),2.04–1.83(m,19H,AcOH),1.82–1.68(m,4H),1.67–1.43(m,9H),1.41–1.31(m,2H),1.31–1.24(m,9H),0.91–0.75(m,24H).
化合物49:Ala-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C61H104N16O19；m/z：683.38997([M+2H]2+)，1365.77292([M+H]+).
1H NMR(600MHz,DMSO-d6)δ8.52–8.41(m,1H),8.34(s,1H),8.28–8.15(m,2H),8.14–8.06(m,1H),8.06–7.93(m,2H),7.83–7.74(m,1H),7.69–7.56(m,2H),7.30–7.18(m,1H),6.76(s,1H),4.59–4.50(m,1H),4.42–4.36(m,1H),4.36–4.08(m,10H),3.79–3.48(m,4H),3.43(d,J＝6.8Hz,1H),2.81–2.67(m,4H),2.48–2.34(m,2H),2.16–2.04(m,4H),2.04–1.40(m,29H,AcOH),1.39–1.25(m,4H),1.22(d,J＝7.1Hz,3H),1.17(d,J＝6.7Hz,6H),0.92–0.70(m,18H).
化合物50:Leu-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C64H110N16O19；m/z：704.41729([M+2H]2+)，1407.82000([M+H]+).
1H NMR(600MHz,D2O)δ4.50(dd,J＝9.5,4.7Hz,1H),4.33(dd,J＝7.9,5.2Hz,2H),4.31–4.14(m,8H),3.99(d,J＝8.3Hz,1H),3.92(t,J＝7.3Hz,1H),3.82–3.73(m,1H),3.73–3.67(m,1H),3.64–3.54(m,2H),2.90(t,J＝7.5Hz,4H),2.68–2.55(m,2H),2.32–2.22(m,4H),2.22–2.12(m,2H),2.08–2.00(m,1H),2.00–1.82(m,13H,AcOH),1.81–1.42(m,17H),1.40–1.29(m,4H),1.29–1.24(m,6H),0.91–0.77(m,24H).
化合物51:Lys-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C64H111N17O19；m/z：711.92148([M+2H]2+)，1422.82606([M+H]+).
1H NMR(600MHz,D2O)δ4.48(dd,J＝9.6,4.6Hz,1H),4.36–4.25(m,5H),4.25–4.14(m,5H),3.99(d,J＝8.2Hz,1H),3.92(t,J＝6.6Hz,1H),3.77(q,J＝7.6Hz,1H),3.73–3.66(m,1H),3.64–3.54(m,2H),2.93–2.87(m,6H),2.65–2.52(m,2H),2.29–2.21(m,4H),2.21–2.13(m,2H),2.08–2.00(m,1H),2.00–1.83(m,16H,AcOH),1.83–1.68(m,7H),1.68–1.50(m,10H),1.49–1.43(m,1H),1.41–1.30(m,6H),1.29(d,J＝7.2Hz,3H),1.26(d,J＝7.2Hz,3H),0.91–0.77(m,18H).
化合物52:Glu-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C63H106N16O21；m/z：712.39490([M+2H]2+)，1423.77335([M+H]+).
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.5,4.7Hz,1H),4.39–4.14(m,10H),4.03–3.93(m,2H),3.83–3.74(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.92–2.86(m,4H),2.72–2.60(m,2H),2.36–2.24(m,6H),2.21–2.12(m,2H),2.08–1.79(m,19H,AcOH),1.79–1.43(m,14H),1.39–1.29(m,4H),1.29–1.24(m,6H),0.90–0.77(m,18H).
化合物53:Lys-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C60H102N16O19；m/z：676.38574([M+2H]2+)，1351.75361([M+H]+).
1H NMR(600MHz,D2O)δ4.50(dd,J＝9.5,4.7Hz,1H),4.36–4.24(m,5H),4.24–4.13(m,4H),4.00–3.94(m,2H),3.93–3.89(m,2H),3.80–3.74(m,1H),3.73–3.66(m,1H),3.63–3.54(m,2H),2.93–2.87(m,4H),2.68–2.55(m,2H),2.29–2.23(m,4H),2.20–2.13(m,2H),2.07–1.69(m,21H,AcOH),1.67–1.42(m,8H),1.42–1.29(m,4H),1.29–1.24(m,6H),0.90–0.77(m,18H).
化合物54:Glu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C59H97N15O21；m/z：676.85849([M+2H]2+)，1352.70235([M+H]+).
1H NMR(600MHz,D2O)δ4.55(dd,J＝9.5,4.7Hz,1H),4.42–4.37(m,1H),4.36–4.13(m,8H),4.03–3.96(m,2H),3.96–3.85(m,2H),3.82–3.73(m,1H),3.73–3.66(m,1H),3.62–3.54(m,2H),2.89(t,J＝7.4Hz,2H),2.76–2.64(m,2H),2.41–2.29(m,4H),2.27(t,J＝7.6Hz,2H),2.21–2.12(m,2H),2.10–1.83(m,15H,AcOH),1.83–1.68(m,4H),1.67–1.43(m,6H),1.39–1.28(m,2H),1.28–1.24(m,6H),0.90–0.77(m,18H).
化合物55:Val-Pro-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)高分辨质谱(TOF-HRMS)，分子式：C70H117N17O21；m/z：766.94110([M+2H]2+)，1532.86012([M+H]+).
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.4,4.9Hz,1H),4.42–4.36(m,2H),4.34(dd,J＝8.3,5.9Hz,1H),4.31–4.24(m,3H),4.24–4.15(m,5H),4.08(d,J＝5.5Hz,1H),3.99(d,J＝8.1Hz,1H),3.83–3.80(m,2H),3.80–3.74(m,1H),3.73–3.63(m,2H),3.63–3.54(m,2H),3.54–3.47(m,1H),2.89(t,J＝7.4Hz,2H),2.74–2.62(m,2H),2.40–2.12(m,8H),2.08–1.83(m,19H,AcOH),1.82–1.68(m,5H),1.67–1.42(m,9H),1.38–1.28(m,2H),1.28–1.23(m,6H),1.00(d,J＝6.9Hz,3H),0.91–0.77(m,27H).
化合物56:Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu(醋酸盐)高分辨质谱(TOF-HRMS)，分子式：C79H132N18O22；m/z：843.49445([M+2H]2+)，1685.97986([M+H]+).
1H NMR(600MHz,D2O)δ4.61–4.57(m,1H),4.57–4.53(m,1H),4.52–4.48(m,1H),4.40(t,J＝7.4Hz,1H),4.37–4.32(m,1H),4.31–4.23(m,4H),4.23–4.10(m,5H),4.08(d,J＝5.4Hz,1H),4.00(d,J＝8.1Hz,1H),3.81–3.73(m,2H),3.73–3.63(m,2H),3.63–3.37(m,4H),2.90(t,J＝7.5Hz,2H),2.76–2.67(m,1H),2.63–2.53(m,1H),2.40–2.28(m,2H),2.28–2.10(m,7H),2.02–1.85(m,18H，AcOH),1.83–1.70(m,6H),1.67–1.46(m,12H),1.40–1.30(m,2H),1.27(t,J＝7.4Hz,6H),1.01(d,J＝6.9Hz,3H),0.90–0.75(m,33H).
化合物57:Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C55H92N14O18；m/z：619.34296([M+2H]2+)，1237.67627([M+H]+).
1H NMR(600MHz,D2O)δ4.57–4.49(m,1H),4.37–4.31(m,1H),4.29(d,J＝7.6Hz,2H),4.25–4.18(m,5H),4.15–4.08(m,1H),3.99(d,J＝8.1Hz,1H),3.81–3.73(m,3H),3.72–3.66(m,1H),3.64–3.54(m,2H),2.88(t,J＝7.5Hz,2H),2.35–2.29(m,2H),2.29–2.22(m,4H),2.20–2.12(m,2H),2.05–1.86(m,15H,AcOH),1.84–1.74(m,4H),1.73–1.68(m,1H),1.67–1.61(m,1H),1.60–1.50(m,4H),1.50–1.42(m,1H),1.36–1.29(m,2H),1.29–1.24(m,6H),0.89–0.85(m,5H),0.84–0.77(m,13H).
化合物58:Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C66H110N16O20；m/z：724.41187([M+2H]2+)，1447.81372([M+H]+).
1H NMR(600MHz,D2O)δ4.60–4.56(m,1H),4.56–4.52(m,1H),4.39–4.32(m,2H),4.31–4.27(m,2H),4.27–4.23(m,2H),4.23–4.15(m,4H),4.12(t,J＝6.7Hz,1H),4.00(d,J＝8.1Hz,1H),3.81–3.75(m,1H),3.70(t,J＝8.3Hz,1H),3.65–3.54(m,3H),3.53–3.47(m,1H),2.93–2.86(m,2H),2.73(d,J＝5.1Hz,1H),2.71(d,J＝5.0Hz,1H),2.61–2.54(m,1H),2.38–2.28(m,2H),2.28–2.23(m,3H),2.22–2.13(m,2H),2.03–1.85(m,16H，AcOH)),1.84–1.68(m,5H),1.67–1.61(m,1H),1.60–1.54(m,3H),1.54–1.45(m,5H),1.42(d,J＝7.0Hz,3H),1.39–1.30(m,2H),1.29(d,J＝7.2Hz,3H),1.26(d,J＝7.1Hz,3H),0.90–0.86(m,5H),0.84–0.78(m,16H),0.77(d,J＝5.3Hz,3H).
化合物59:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Ala-Gly-Leu-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C78H129N19O25；m/z：866.97784([M+2H]2+)，1732.94507([M+H]+).
1H NMR(600MHz,D2O)δ4.58–4.53(m,2H),4.44–4.41(m,1H),4.36–4.33(m,1H),4.32–4.27(m,4H),4.26–4.17(m,7H),4.00(d,J＝8.0Hz,1H),3.85–3.82(m,2H),3.80–3.75(m,1H),3.73–3.67(m,1H),3.64–3.54(m,2H),3.36–3.25(m,2H),2.94–2.85(m,2H),2.78–2.71(m,2H),2.71–2.65(m,1H),2.65–2.58(m,1H),2.40–2.29(m,3H),2.27–2.22(m,2H),2.21–2.13(m,2H),2.02–1.85(m,18H,AcOH)),1.81–1.75(m,3H),1.74–1.68(m,1H),1.68–1.62(m,1H),1.62–1.43(m,12H),1.39–1.31(m,2H),1.30(d,J＝7.0Hz,6H),1.27(d,J＝7.2Hz,3H),0.90–0.86(m,5H),0.85–0.80(m,16H),0.79(d,J＝6.3Hz,3H),0.78–0.75(m,6H).
化合物60:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Val-Pro-Leu(醋酸盐)高分辨质谱(TOF-HRMS)，分子式：C79H132N18O22；m/z：843.49530([M+2H]2+)，1685.98096([M+H]+).
1H NMR(600MHz,D2O)δ4.58–4.50(m,2H),4.37–4.28(m,5H),4.28–4.16(m,6H),4.15–4.08(m,1H),4.00(d,J＝8.0Hz,1H),3.82–3.73(m,2H),3.72–3.67(m,1H),3.64–3.56(m,3H),3.37–3.32(m,1H),3.31–3.26(m,1H),2.93–2.86(m,2H),2.70–2.63(m,1H),2.59–2.52(m,1H),2.40–2.30(m,3H),2.29–2.22(m,2H),2.22–2.14(m,3H),2.03–1.82(m,19H,AcOH),1.82–1.69(m,4H),1.68(s,1H),1.62–1.44(m,11H),1.40–1.31(m,2H),1.31(d,J＝7.3Hz,3H),1.27(d,J＝7.2Hz,3H),0.94–0.85(m,9H),0.85–0.81(m,18H),0.79(d,J＝6.5Hz,6H),0.76(d,J＝5.7Hz,3H).
化合物61:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Pro-Val-Pro-Leu高分辨质谱(TOF-HRMS)，分子式：C84H139N19O23；m/z：892.02161([M+2H]2+).
1H NMR(600MHz,D2O)δ4.48–4.39(m,3H),4.28–4.16(m,7H),4.15–4.06(m,5H),4.01(dd,J＝9.7,5.2Hz,1H),3.89(d,J＝8.1Hz,1H),3.72–3.64(m,2H),3.64–3.56(m,2H),3.54–3.35(m,4H),3.26–3.14(m,2H),2.79(t,J＝7.6Hz,2H),2.61–2.53(m,1H),2.48–2.40(m,1H),2.30–2.19(m,3H),2.18–2.12(m,2H),2.10–2.03(m,3H),1.92–1.71(m,24H,AcOH),1.71–1.31(m,17H),1.30–1.21(m,2H),1.20(d,J＝7.3Hz,3H),1.16(d,J＝7.2Hz,3H),0.85–0.67(m,36H).
化合物62:
Val-Pro-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Val-Pro-Leu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C92H155N21O25；m/z：978.08408([M+2H]2+)，1955.14559([M+H]+).
1H NMR(600MHz,D2O)δ4.57–4.51(m,2H),4.39(t,J＝7.5Hz,1H),4.37–4.27(m,5H),4.27–4.15(m,7H),4.11(dd,J＝9.1,5.6Hz,1H),4.08(d,J＝5.4Hz,1H),3.99(d,J＝8.0Hz,1H),3.84–3.80(m,2H),3.79–3.64(m,3H),3.63–3.35(m,4H),2.89(t,J＝7.5Hz,2H),2.72–2.65(m,1H),2.39–2.27(m,2H),2.39–2.27(m,2H),2.27–2.06(m,7H),2.03–1.68(m,27H,AcOH),1.68–1.42(m,15H),1.39–1.28(m,2H),1.28–1.24(m,6H),1.00(d,J＝7.0Hz,3H),0.91–0.77(m,42H),0.75(d,J＝5.8Hz,3H).
化合物63:
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp
高分辨质谱(TOF-HRMS)，分子式：C111H182N28O35；m/z：823.79035([M+3H]3+)，1235.17867([M+2H]2+).
1H NMR(600MHz,D2O)δ4.59–4.51(m,3H),4.39(dd,J＝6.8,5.2Hz,1H),4.37–4.32(m,2H),4.31–4.18(m,14H),4.02–3.97(m,2H),3.83(s,2H),3.80–3.67(m,3H),3.62–3.55(m,3H),3.37–3.24(m,2H),2.92–2.86(m,4H),2.74–2.60(m,4H),2.41–2.22(m,9H),2.20–2.13(m,3H),2.08–1.82(m,35H),1.82–1.67(m,8H),1.67–1.42(m,12H),1.40–1.30(m,4H),1.30–1.23(m,12H),0.92–0.76(m,36H).
化合物64:
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Le u-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C117H193N29O36；m/z：861.48234([M+3H]3+)，1291.71630([M+2H]2+).
1H NMR(600MHz,D2O)δ4.59–4.52(m,3H),4.39(dd,J＝6.9,5.1Hz,1H),4.37–4.32(m,2H),4.32–4.27(m,5H),4.26–4.24(m,1H),4.24–4.18(m,9H),4.00–3.97(m,2H),3.83–3.80(m,2H),3.80–3.74(m,2H),3.73–3.66(m,2H),3.62–3.55(m,3H),3.36–3.25(m,2H),2.92–2.86(m,4H),2.75–2.64(m,3H),2.61–2.55(m,1H),2.41–2.31(m,4H),2.30–2.12(m,8H),2.07–1.83(m,36H,AcOH),1.82–1.68(m,8H),1.67–1.42(m,15H),1.41–1.30(m,4H),1.30–1.24(m,12H),0.92–0.74(m,42H).
化合物65:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Leu
高分辨质谱(TOF-HRMS)，分子式：C64H107N15O19；m/z：695.90275([M+2H]2+)，1390.78841([M+H]+).
化合物66:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Ala(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C61H101N15O19；m/z：674.87902([M+2H]2+).
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.7Hz,1H),4.34(dd,J＝8.4,5.8Hz,1H),4.31–4.27(m,3H),4.27–4.17(m,6H),4.06(q,J＝7.2Hz,1H),3.98(d,J＝8.1Hz,1H),3.80–3.74(m,1H),3.73–3.65(m,1H),3.63–3.54(m,2H),3.37–3.24(m,2H),2.89(t,J＝7.6Hz,2H),2.40–2.22(m,7H),2.22–2.12(m,2H),2.05–1.81(m,19H,AcOH),1.81–1.66(m,4H),1.66–1.42(m,6H),1.41–1.30(m,2H),1.30–1.23(m,9H),0.91–0.77(m,18H).
化合物67:Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C53H89N13O17；m/z：590.83474([M+2H]2+)，1180.65606([M+H]+).
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.4,4.6Hz,1H),4.37–4.31(m,1H),4.31–4.15(m,6H),4.13–4.06(m,1H),4.02–3.94(m,2H),3.83–3.66(m,2H),3.64–3.53(m,2H),2.88(t,J＝7.5Hz,2H),2.38–2.30(m,2H),2.29–2.22(m,4H),2.21–2.12(m,2H),2.06–1.45(m,26H,AcOH),1.43(d,J＝7.2Hz,3H),1.35–1.28(m,2H),1.27(d,J＝7.2Hz,3H),0.92–0.75(m,18H).
化合物68:Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C69H116N16O20；m/z：745.43743([M+2H]2+)，1489.85546([M+H]+).
1H NMR(600MHz,D2O)δ4.53(dd,J＝9.5,4.8Hz,1H),4.41–4.31(m,2H),4.31–4.26(m,2H),4.26–4.14(m,6H),4.13–4.06(m,2H),4.03–3.96(m,1H),3.80–3.49(m,5H),2.88(t,J＝7.5Hz,2H),2.40–2.29(m,2H),2.29–2.12(m,8H),2.05–1.68(m,24H,AcOH),1.67–1.43(m,9H),1.38–1.28(m,2H),1.28–1.24(m,6H),1.00(d,J＝6.9Hz,3H),0.91–0.77(m,27H).
化合物69:Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C48H82N12O14；m/z：526.31294([M+2H]2+)，1051.61322([M+H]+.
1H NMR(600MHz,D2O)δ4.52(dd,J＝9.6,4.7Hz,1H),4.34(dd,J＝8.4,5.9Hz,1H),4.31–4.19(m,5H),4.08(dd,J＝8.8,4.8Hz,1H),4.01–3.95(m,2H),3.80–3.67(m,2H),3.65–3.54(m,2H),2.89(t,J＝7.5Hz,2H),2.34–2.26(m,2H),2.26–2.12(m,4H),2.04–1.69(m,18H,AcOH),1.68–1.45(m,6H),1.43(d,J＝7.2Hz,3H),1.39–1.28(m,2H),1.27(d,J＝7.2Hz,3H),0.93–0.76(m,18H).
化合物70:Arg-Lys-Asp-Val-Tyr-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp1H NMR(600MHz,D2O)δ7.02(d,J＝8.5Hz,2H),6.72(d,J＝8.4Hz,2H),4.54–4.44(m,3H),4.36–4.24(m,6H),4.23–4.14(m,4H),4.01–3.97(m,1H),3.97–3.91(m,2H),3.81–3.64(m,4H),3.60–3.52(m,2H),3.15–3.06(m,2H),3.02–2.96(m,1H),2.91–2.79(m,5H),2.68–2.46(m,4H),2.32–2.21(m,4H),2.20–2.10(m,2H),2.07–1.99(m,1H),1.99–1.67(m,25H),1.66–1.42(m,11H),1.37–1.28(m,3H),1.28–1.23(m,6H),0.91–0.74(m,18H),0.68(dd,J＝6.7,2.7Hz,6H).
化合物71:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Cys-Gly(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C63H104N16O20S；m/z：719.37693([M+2H]2+)，1437.73683([M+H]+).
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.7Hz,1H),4.46(dd,J＝7.2,5.2Hz,1H),4.34(dd,J＝8.3,5.9Hz,1H),4.31–4.26(m,4H),4.26–4.14(m,5H),3.98(d,J＝8.0Hz,1H),3.81–3.74(m,1H),3.71(s,2H),3.71–3.67(m,1H),3.63–3.54(m,2H),3.36–3.25(m,2H),2.91–2.79(m,4H),2.40–2.23(m,7H),2.22–2.12(m,2H),2.08–1.85(m,19H,AcOH),1.81–1.61(m,5H),1.61–1.43(m,5H),1.39–1.30(m,2H),1.30(d,J＝7.3Hz,3H),1.26(d,J＝7.2Hz,3H),0.93–0.76(m,18H).
化合物72:
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C99H161N23O29；m/z：713.40155([M+3H]3+)，1069.59802([M+2H]2+).
1H NMR(600MHz,D2O)δ4.59–4.54(m,2H),4.42–4.38(m,1H),4.37–4.33(m,3H),4.30(t,J＝7.4Hz,5H),4.28–4.25(m,2H),4.25–4.20(m,6H),4.20–4.11(m,2H),4.00(d,J＝8.2Hz,1H),3.81–3.74(m,3H),3.73–3.67(m,2H),3.64–3.55(m,5H),3.37–3.24(m,2H),2.90(t,J＝7.4Hz,2H),2.75–2.65(m,2H),2.42–2.31(m,5H),2.28(t,J＝7.6Hz,3H),2.22–2.13(m,5H),2.07–1.83(m,30H,AcOH),1.83–1.74(m,7H),1.73–1.69(m,1H),1.68–1.62(m,1H),1.62–1.50(m,6H),1.50–1.42(m,2H),1.39–1.31(m,2H),1.31–1.25(m,12H),0.90–0.86(m,12H),0.85–0.77(m,24H).
化合物73:Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Glu-Cys-Gly
高分辨质谱(TOF-HRMS)，分子式：C73H120N18O24S；m/z：833.42972([M+2H]2+)，1665.83408([M+H]+).
化合物74:Ala-Ala-Ala-Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C72H119N19O23；m/z：809.94612([M+2H]2+)，1618.87350([M+H]+).
1H NMR(600MHz,D2O)δ4.57–4.45(m,2H),4.39–4.31(m,2H),4.31–4.13(m,11H),3.98(dd,J＝7.8,5.9Hz,2H),3.80–3.74(m,1H),3.73–3.66(m,2H),3.63–3.47(m,3H),2.89(t,J＝7.4Hz,2H),2.73–2.61(m,2H),2.39–2.29(m,2H),2.27(t,J＝7.6Hz,2H),2.24–2.12(m,3H),2.08–1.68(m,21H,AcOH),1.68–1.44(m,6H),1.43(d,J＝7.1Hz,3H),1.40–1.30(m,2H),1.30–1.23(m,18H),0.92–0.77(m,18H).
化合物75:Ala-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp(醋酸盐)
高分辨质谱(TOF-HRMS)，分子式：C81H133N19O23；m/z：870.99892([M+2H]2+).
1H NMR(600MHz,D2O)δ4.54(dd,J＝9.5,4.9Hz,1H),4.49(dd,J＝9.7,4.9Hz,1H),4.42(dd,J＝8.3,6.4Hz,1H),4.40–4.24(m,9H),4.23–4.10(m,4H),3.99(d,J＝8.2Hz,1H),3.80–3.67(m,3H),3.64–3.43(m,6H),2.89(t,J＝7.4Hz,2H),2.73–2.61(m,2H),2.40–2.29(m,2H),2.27(t,J＝7.6Hz,2H),2.25–2.08(m,5H),2.07–1.68(m,29H,AcOH),1.68–1.44(m,9H),1.42(d,J＝7.1Hz,3H),1.37–1.29(m,2H),1.29–1.22(m,6H),0.92–0.76(m,30H).化合物76：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp醋酸盐1H NMR(600MHz,DMSO)δ8.27(d,J＝7.6Hz,1H),8.21(d,J＝7.8Hz,1H),8.09(d,J＝7.5Hz,1H),8.03(d,J＝7.9Hz,1H),7.99(d,J＝7.4Hz,1H),7.94(dd,J＝16.7,8.0Hz,2H),7.58(d,J＝6.3Hz,1H),7.51(d,J＝8.6Hz,1H),7.16(s,1H),6.70(s,1H),4.48(dd,J＝13.3,7.9Hz,1H),4.39(dd,J＝8.2,4.2Hz,1H),4.35-4.21(m,6H),4.18-4.03(m,3H),3.71-3.47(m,5H),2.93-2.69(m,4H),2.45-2.32(m,2H),2.25(t,J＝7.7Hz,2H),2.08(t,J＝7.9Hz,2H),
2.01-1.93(m,3H),1.93-1.84(m,14H,AcOH),1.84-1.76(m,3H),1.75-1.57(m,8H),1.54-1.39(m,5H),1.36-1.27(m,2H),1.21-1.10(m,6H),0.91-0.74(m,18H).
实施例2:多肽(化合物76)对乙醇诱导的小鼠胃溃疡模型的抗溃疡作用
1、实验动物：SPF级C57BL/6小鼠，成都药康生物科技有限公司，动物许可证号：SCXK(川)2020-034。
2、方法：实验动物适应性喂养后，小鼠按随机分组法分成4组，每组10只，即：对照组(空白组)、模型组(无水乙醇造模)、阳性药物组(替普瑞酮160mg/kg)，化合物76组(1mg/kg)。动物分组后，对照组及模型组给予纯水治疗外，其它给药组给予相应药物治疗，每天一次，连续8天。第7天给药后所有动物禁食不禁水24h，于第8天给药30min后对各组(除对照组外)小鼠经口灌胃给予0.15mL的无水乙醇造模，1h后CO2过量吸入处死动物，结扎胃贲门和夹闭幽门，摘取全胃。向胃体内注入1％甲醛溶液1mL，结扎贲门，取出胃后即放入1％甲醛溶液中固定25min。沿胃大弯剪开，生理盐水清洗干净胃内容物，平铺后计算溃疡指数。溃疡指数计算方法：条索状损伤长度大于1mm者，测量其长度，每毫米计1分；若其宽度大于1mm，将计分按宽度的毫米数加倍；长度小于1mm计0.5分，将计分相加得出该动物的溃疡指数。
3、结果：
在小鼠乙醇诱导的胃溃疡模型中，化合物76每天一次连续8天经口灌胃可显著使小鼠胃溃疡指数降低，且效果优于阳性药物组(表3)，结果表明化合物76治疗胃溃疡作用显著。
表3.受试药对乙醇致胃溃疡小鼠溃疡指数的影响(n＝10，
)
注：与对照组相比，##P<0.01；与模型组相比，*P<0.05，**P<0.01
实施例3：化合物1-76样品对乙醇诱导的小鼠胃溃疡模型的抗溃疡活性
1、实验动物：SPF级C57BL/6小鼠，成都药康生物科技有限公司，动物许可证号：SCXK(川)2020-034
2、方法：
实验动物适应性喂养后，实验前1天给药后所有动物开始禁食不禁水24h。造模前实验小鼠随机分组：空白组5只、模型组10只、各给药组每组10只，除空白组及模型组灌胃给予纯化水以外，给药组均按照0.2mg/kg的给药剂量灌胃给予不同受试样品，给药1小时后，各组小鼠经口灌胃给予0.9ml/kg的无水乙醇造模，1h后利用脱颈法处死动物，结扎胃贲门和夹闭幽门，摘取全胃。向胃体内注入1％甲醛溶液1mL，结扎贲门，取出胃后即放入1％甲醛溶液中。浸泡30min后取出胃组织，沿胃大弯剪开，使用生理盐水冲洗干净胃内容物，平铺后观察并测定小鼠胃黏膜的损伤，计算溃疡指数和溃疡抑制率。
溃疡指数计算方法：条索状损伤长度大于1mm者，测量其长度，每毫米计1分；若其宽度大于1mm，将计分按宽度的毫米数加倍；长度小于1mm计0.5分，将计分相加得出该动物的溃疡指数。
溃疡抑制率＝(模型组溃疡指数-给药组溃疡指数)/模型组溃疡指数×100％；
相对溃疡抑制率＝(测试化合物溃疡抑制率)/(化合物76溃疡抑制率)。
3、结果：表5示出了化合物1-76相对于化合物76的相对抗溃疡活性：
表5小鼠乙醇造模单次给药抗溃疡活性
*注释：每个化合物的抗溃疡作用经多批试验完成，为便于比较，抗溃疡活性以相对溃疡抑制率(每批试验都以化合物76作为对照组)的平均值表示。
相对溃疡抑制率＝(测试化合物溃疡抑制率)/(化合物76溃疡抑制率)
相对溃疡抑制率>1.50，表示为“+++++”；
相对溃疡抑制率>1.20，表示为“++++”；
相对溃疡抑制率为0.9-1.20，表示为“+++”；
相对溃疡抑制率为0.6-0.9，表示为“++”；
“NA”表示未检测。
实施例4：化合物34,36,38,39样品对小鼠胃类器官生长是否具有促进作用
实验方法：冻存的小鼠类器官复苏后在6孔板中进行扩增，待类器官生长到足量后取出需要处理的6孔板，去除旧培养基，每孔加入Dispase II，用1mL移液枪吸头回收6孔板中的Matrigel胶滴，并转移至15mL离心管中，并用L TrypLE消化成单细胞。离心后去掉上清，加入1-3mL DMEM/F-12重悬，混匀并取10μL进行细胞计数，计算重悬液中细胞总数。
取相应体积的细胞悬液并用适量Matrigel混匀，取30μL Matrigel(约含500个细胞)接种于96孔板中；将接种后的96孔板放置于37℃培养箱中20min，以使Matrigel凝固。对照组加入140μL类器官培养基，给药组加入140μL含不同浓度的延长肽类器官培养基。每种延长肽设置三个浓度，分别是1μM、5μM和10μM。将孔板放入37℃培养箱培养9天，每48小时进行换液。在第9天取出孔板，用CelltiterGlo(CTG)分析类器官活率。
实验结果见图2-图5。其中，图2(*p<0.05,**p<0.01,***p<0.001与对照组相比，单向方差分析)和图4(*p<0.05,**p<0.01与对照组相比，单向方差分析)各浓度与对照组相比显著增加了CTG读值，有一定剂量依赖性，在5μM浓度下趋势最优。图3(*p<0.05,**p<0.01与对照组组相比，单向方差分析)中1μM和5μM与对照组相比显著增加了CTG读值，有一定剂量依赖性；在10μM有增加的趋势但没有显著性差异。图5(与对照组相比无显著性差异，单向方差分析)在1μM和5μM浓度下CTG读值有增加的趋势但没有显著性差异；在10μM浓度下与对照组相比没有明显的趋势。提示化合物34,36,38对小鼠胃类器官的生长具有促进作用，并有一定的剂量依赖性。
尽管本发明披露了上述实施例，但本发明的实施方式并不限于上述实施例，其他的任何未背离本发明的改变、修饰、替代、组合、简化，均应为等效的置换方式均包含在本发明的保护范围之内。
Claims (11)
1.式(I)的化合物或其生理学上相容的盐，其中所述式(I)的化合物如下：
H-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Xaa8-Ala-Ala-Glu-Pro-Val-Pro-Leu
-Xaa9-Xaa10-Xaa11-Xaa12-Xaa13-Xaa14-Xaa15-Xaa16-Xaa17-Xaa18-Xaa19-Xaa20-Xaa21-Xaa22-
Xaa23-Xaa24-Xaa25-OH(I)
其中
Xaa1为Ala或缺失；
Xaa2为Ala或缺失；
Xaa3为Ala、Arg、Glu或缺失；
Xaa4为Pro、Lys、Ala或缺失；
Xaa5为Glu、Val、Asp、Gln、Lys、Ala、Pro或缺失；
Xaa6为Pro、Gln、Lys、Val、Ala或缺失；
Xaa7为Ala、Leu、Gly、Lys、Gln、Glu、Val、Asp、Pro、Tyr或缺失；
Xaa8为Pro、Leu、Lys、Glu、Gly、Ile、Leu、Val、Gly、Ala或缺失；
Xaa9-Xaa10-Xaa11为Val-Lys-Gln、Ala-Gly-Leu、Ala-Ala-Val、Val-Pro-Ala；
Xaa12为Asp、Ala、Gln、Lys、Glu、Ala或缺失；
Xaa13为Ala、Leu、Gly、Lys、Gln、Asp、Cys、Glu或缺失；
Xaa14为Ala、Leu、Val、Pro、Gly、Glu或缺失；
Xaa15-Xaa16为Gly-Leu、Pro-Leu、Val-Pro、Pro-Leu、Ala-Glu、Ala-Ala、Val-Pro、Cys-Gly或缺失；
Xaa17为Asp、Leu、Pro、Glu或缺失；
Xaa18-Xaa19-Xaa20-Xaa21为Val-Lys-Gln-Asp、Pro-Val-Pro-Leu、Val-Pro-Leu-Val或缺失；
Xaa22-Xaa23-Xaa24为Lys-Gln-Asp、Val-Lys-Gln或缺失；
以及Xaa25为Asp或缺失；
所述化合物至少为10肽。
2.根据权利要求1的化合物或其生理学上相容的盐，其中所述化合物选自：
化合物1：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物2：Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物3：Gly-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物4：Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物5：Gln-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物6：Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物7：Glu-Pro-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物8：Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物9：Val-Pro-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物10：Asp-Gln-Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物11：ln-Lys-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物12：Lys-Val-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物13：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Ala、化合物14：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu、化合物15：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gly、化合物16：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Lys、化合物17：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gln、化合物18：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Asp、化合物19：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Ala、
化合物20：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Gln、
化合物21：Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物22：Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物23：Glu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物24：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Lys、
化合物25：Ala-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物26：Ala-Ile-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物27：Ala-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物28：Ala-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物29：Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物30：Leu-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物31：Lys-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物32：Glu-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物33：Lys-Ala-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物34：Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物35：Val-Lys-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物36：Ala-Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物37：Val-Pro-Leu-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物38：Pro-Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、化合物39：Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物40：Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物41：
Ala-Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物42：
Ala-Ala-Glu-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物43：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Ala-Gly-Leu-Asp、
化合物44：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Ala-Ala-Val-Asp、
化合物45：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物46：Asp-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物47：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Ala、
化合物48：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Ala-Leu、
化合物49：Ala-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物50：Leu-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物51：Lys-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物52：Glu-Lys-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物53：Lys-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物54：Glu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物55：Val-Pro-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物56：Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu、
化合物57：Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物58：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu、
化合物59：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Ala-Gly-Leu-Asp、化合物60：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Val-Pro-Leu、
化合物61：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Pro-Val-Pro-Leu、
化合物62：
Val-Pro-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Val-Pro-Leu、
化合物63：
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物64：
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物65：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Leu、
化合物66：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Ala、
化合物67：Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物68：Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu、
化合物69：Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln、
化合物70：Arg-Lys-Asp-Val-Tyr-Gly-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物71：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Glu-Cys-Gly、
化合物72：
Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-As p、
化合物73：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp-Leu-Glu-Cys-Gly、
化合物74：Ala-Ala-Ala-Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物75：Ala-Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物76：Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp。
3.根据权利要求1或2的化合物或其生理学上相容的盐，其特征在于：所述Xaa9-Xaa10-Xaa11为Val-Lys-Gln。
4.根据权利要求3的化合物或其生理学上相容的盐，其特征在于：所述Xaa12为Asp。
5.根据权利要求3的化合物或其生理学上相容的盐，其特征在于：所述Xaa12为Glu。
6.根据权利要求4的化合物或其生理学上相容的盐，其特征在于：所述Xaa8为Pro、Val或Leu。
7.根据权利要求6的化合物或其生理学上相容的盐，其中所述化合物选自：
化合物1：Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物34：Ala-Ala-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物36：Ala-Glu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物39：Pro-Val-Pro-Leu-Pro-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp、
化合物37：Val-Pro-Leu-Val-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp或
化合物38：Pro-Val-Pro-Leu-Ala-Ala-Glu-Pro-Val-Pro-Leu-Val-Lys-Gln-Asp。
8.权利要求1或2所述的化合物或其生理学上相容的盐在制备用于修复皮肤损伤或黏膜损伤的药物中的用途。
9.根据权利要求8的用途，其中所述黏膜损伤是消化系统、呼吸系统等腔道内黏膜损伤。
10.根据权利要求9的用途，其中所述消化系统黏膜损伤与口腔、食道、胃肠疾病相关，所述口腔疾病包括口腔溃疡、口腔炎、牙龈炎、牙周炎等；所述食道疾病包括食管炎、食管溃疡等；所述胃肠疾病包括慢性胃炎、慢性萎缩性胃炎、急性胃炎、胃十二指肠溃疡、功能性胃肠道疾病、消化不良、癌前病变、消化系统肿瘤、胃肠道出血、胃食管返流疾病、急慢性肠炎、溃疡性结肠炎、克罗恩病和放化疗引起的黏膜损伤；所述皮肤损伤与表皮炎症、机械及手术创面、烧伤及烫伤、溃疡、瘘管、褥疮、放化疗引起的皮肤损伤等疾病相关。
11.一种药物、食品、保健品或化妆品、日化品组合物，所述组合物包括至少一种权利要求1或2所述的化合物或其生理学上相容的盐以及生理学上可接受的载体。
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