肽Codesane的结构修饰及抗肿瘤活性研究:新型钉接肽抗肿瘤药物的发现

IF 1.8 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
Qingmei Li, Lijuan Qiu, Yong Li
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引用次数: 0

摘要

新的候选分子的发现可能会改变癌症治疗,具有重要的临床意义。Codesane (COD)是一种阳离子α-螺旋型两性抗菌肽,是从野生大蜂毒液中提取的18个氨基酸的肽。通过固相肽合成的COD在体外显示出明显的抗肿瘤活性。然而,其作为药物的应用受到构象灵活性、血清稳定性差和选择性低的限制。本研究主要是设计、合成和评价一系列采用全烃钉接策略的COD衍生物。与原始肽COD相比,这些钉接衍生物在α-螺旋度、血清抗性、抗肿瘤活性和细胞选择性方面均有显著增强。值得注意的是,装订衍生物COD-5具有高螺旋度、良好的血清稳定性和良好的选择性,具有开发新型抗肿瘤药物的潜力,而COD-3具有高选择性和良好的抗肿瘤活性,是开发新型乳腺癌治疗药物的首选候选者。这些发现为开发创新和高效的抗肿瘤疗法提供了坚实的基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Structural Modification and Antitumor Activity Study of Peptide Codesane: Discovery of Novel Stapled Peptide Antitumor Agents

Structural Modification and Antitumor Activity Study of Peptide Codesane: Discovery of Novel Stapled Peptide Antitumor Agents

The discovery of novel candidate molecules that may transform cancer treatment carries significant clinical implications. Codesane (COD), an 18-amino acid peptide extracted from the wild bee venom of Colletes daviesanus, is categorized as a cationic α-helical amphipathic antimicrobial peptide. COD, produced via solid-phase peptide synthesis, displayed significant antitumor activity in vitro. However, its application as a drug is restricted by conformational flexibility, poor serum stability, and low selectivity. This research focused on designing, synthesizing, and evaluating a series of stapled COD derivatives by all-hydrocarbon stapling strategy. Compared to the original peptide COD, several of these stapled derivatives showed significant enhancements in α-helicity, serum resistance, antitumor activity, and cell selectivity. Significantly, the stapled derivative COD-5, which possesses high helicity, good serum stability, and favorable selectivity, shows promising potential for novel antitumor drug development, whereas COD-3, characterized by high selectivity and good antitumor activity, serves as a preferred candidate for novel breast cancer therapeutic drugs. These findings provide a solid foundation for developing innovative and highly effective antitumor therapies.

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来源期刊
Journal of Peptide Science
Journal of Peptide Science 生物-分析化学
CiteScore
3.40
自引率
4.80%
发文量
83
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.
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