Hydrocarbon stapling modification of peptide alyteserin-2a: Discovery of novel stapled peptide antitumor agents.

IF 1.8 4区生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Peptide Science Pub Date : 2022-07-01 Epub Date: 2022-02-01 DOI:10.1002/psc.3401

Ziqiang Yu, Hua Tang, Wei Cong, Fei Gao, Huaqiang Li, Honggang Hu, Xiaoyan Wang, Shipeng He

{"title":"Hydrocarbon stapling modification of peptide alyteserin-2a: Discovery of novel stapled peptide antitumor agents.","authors":"Ziqiang Yu, Hua Tang, Wei Cong, Fei Gao, Huaqiang Li, Honggang Hu, Xiaoyan Wang, Shipeng He","doi":"10.1002/psc.3401","DOIUrl":null,"url":null,"abstract":"Alyteserin-2a (ILGKLLSTAAGLLSNLNH2 ) is isolated from the skin exudates of midwife toad and has a wide range of biological applications. However, the use of alyteserin-2a as an antitumor agent is limited due to its structural flexibility. In this study, a series of stapled peptides were prepared through hydrocarbon stapling modification without destroying the key residues, and their chemical and biological properties were further evaluated for enhancing the application potential of alyteserin-2a in the field of antitumor drugs development. Among them, alyteserin-2a-Sp3 displayed significant improvement in helicity levels, protease resistance, and antitumor activity compared to that of the template peptide alyteserin-2a, indicating that alyteserin-2a-Sp3 had a potential to become a lead compound for the development of novel antitumor drugs. This study confirms the important effect of hydrocarbon stapling strategy on the secondary structure, hydrolase stability, and biological activity of alyteserin-2a.","PeriodicalId":16946,"journal":{"name":"Journal of Peptide Science","volume":"28 7","pages":"e3401"},"PeriodicalIF":1.8000,"publicationDate":"2022-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Peptide Science","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1002/psc.3401","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2022/2/1 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}

引用次数: 1

Abstract

Alyteserin-2a (ILGKLLSTAAGLLSNLNH₂ ) is isolated from the skin exudates of midwife toad and has a wide range of biological applications. However, the use of alyteserin-2a as an antitumor agent is limited due to its structural flexibility. In this study, a series of stapled peptides were prepared through hydrocarbon stapling modification without destroying the key residues, and their chemical and biological properties were further evaluated for enhancing the application potential of alyteserin-2a in the field of antitumor drugs development. Among them, alyteserin-2a-Sp3 displayed significant improvement in helicity levels, protease resistance, and antitumor activity compared to that of the template peptide alyteserin-2a, indicating that alyteserin-2a-Sp3 had a potential to become a lead compound for the development of novel antitumor drugs. This study confirms the important effect of hydrocarbon stapling strategy on the secondary structure, hydrolase stability, and biological activity of alyteserin-2a.

查看原文本刊更多论文

肽alyteserin-2a的烃类钉接修饰:新型钉接肽抗肿瘤药物的发现。

Alyteserin-2a (ILGKLLSTAAGLLSNL - NH2)是从助产士蟾蜍的皮肤渗出液中分离出来的，具有广泛的生物学应用。然而，alyteserin-2a作为抗肿瘤药物的使用由于其结构的灵活性而受到限制。本研究在不破坏关键残基的情况下，通过烃类钉接改性制备了一系列钉接肽，并进一步评价了其化学和生物学特性，以提升alyteserin-2a在抗肿瘤药物开发领域的应用潜力。其中，与模板肽alyteserin-2a相比，alyteserin-2a- sp3在螺旋度水平、蛋白酶抗性和抗肿瘤活性方面均有显著提高，表明alyteserin-2a- sp3有潜力成为开发新型抗肿瘤药物的先导化合物。本研究证实了烃类钉接策略对alyteserin-2a的二级结构、水解酶稳定性和生物活性的重要影响。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Journal of Peptide Science 生物-分析化学

CiteScore

3.40

自引率

4.80%

发文量

审稿时长

1.7 months

期刊介绍： The official Journal of the European Peptide Society EPS The Journal of Peptide Science is a cooperative venture of John Wiley & Sons, Ltd and the European Peptide Society, undertaken for the advancement of international peptide science by the publication of original research results and reviews. The Journal of Peptide Science publishes three types of articles: Research Articles, Rapid Communications and Reviews. The scope of the Journal embraces the whole range of peptide chemistry and biology: the isolation, characterisation, synthesis properties (chemical, physical, conformational, pharmacological, endocrine and immunological) and applications of natural peptides; studies of their analogues, including peptidomimetics; peptide antibiotics and other peptide-derived complex natural products; peptide and peptide-related drug design and development; peptide materials and nanomaterials science; combinatorial peptide research; the chemical synthesis of proteins; and methodological advances in all these areas. The spectrum of interests is well illustrated by the published proceedings of the regular international Symposia of the European, American, Japanese, Australian, Chinese and Indian Peptide Societies.