螺旋轮旋转优化两亲抗菌肽。

IF 3.4 4区 医学 Q2 CHEMISTRY, MEDICINAL
ChemMedChem Pub Date : 2025-09-08 DOI:10.1002/cmdc.202500316
Hai Bui Thi Phuong, Nguyen-Thi Phuong, Le Minh Bui, Hue Pham Thi, Thi Thu Phuong Tran, Thang Nguyen Quoc, Hiep Tuan Tran, Minh Nguyen Hong, Huy Luong Xuan
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引用次数: 0

摘要

抗菌肽(AMPs)已成为对抗耐药病原体和某些癌症类型的有希望的候选者。然而,它们的治疗应用往往受到不希望的溶血活性的限制,而许多amp仅表现出中等效力。本文探讨了“螺旋轮旋转”策略作为一种简单、经济、模块化的方法,在不改变两亲性α-螺旋AMPs氨基酸组成的情况下优化其药理特性。以BP52为模型肽,开发了6个旋转变体(BP52- a1至BP52- a6)和2个序列修饰衍生物(BP52- b1和BP52- b2),以评估其抗菌、抗癌和溶血特性。一些衍生物,特别是BP52-A6,表现出增强的抗菌活性和减少溶血,同时保持或提高对癌细胞的效力。重要的是,与BP52相比,所有衍生物的溶血活性都大大降低。这些发现突出了螺旋轮旋转作为一种有价值的肽工程策略的潜力,可以微调AMPs的选择性和多功能性,用于治疗应用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Optimizing Amphipathic Antimicrobial Peptides via Helical Wheel Rotation.

Antimicrobial peptides (AMPs) have emerged as promising candidates for combating drug-resistant pathogens and certain cancer types. However, their therapeutic applications are often limited by undesired hemolytic activity, while many AMPs exhibit only moderate potency. Herein, the "helical wheel rotation" strategy as a simple, cost-effective, and modular approach to optimize the pharmacological properties of amphipathic α-helical AMPs without altering their amino acid composition is explored. Using BP52 as a model peptide, six rotational variants (BP52-A1 to BP52-A6) and two sequence-modified derivatives (BP52-B1 and BP52-B2) are developed to assess their antimicrobial, anticancer, and hemolytic properties. Several derivatives, especially BP52-A6, exhibit enhanced antimicrobial activity and reduced hemolysis while maintaining or improving potency toward cancer cells. Importantly, all derivatives show substantially reduced hemolytic activity compared to BP52. These findings highlight the potential of helical wheel rotation as a valuable peptide engineering strategy to fine-tune selectivity and multifunctionality of AMPs for therapeutic applications.

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来源期刊
ChemMedChem
ChemMedChem 医学-药学
CiteScore
6.70
自引率
2.90%
发文量
280
审稿时长
1 months
期刊介绍: Quality research. Outstanding publications. With an impact factor of 3.124 (2019), ChemMedChem is a top journal for research at the interface of chemistry, biology and medicine. It is published on behalf of Chemistry Europe, an association of 16 European chemical societies. ChemMedChem publishes primary as well as critical secondary and tertiary information from authors across and for the world. Its mission is to integrate the wide and flourishing field of medicinal and pharmaceutical sciences, ranging from drug design and discovery to drug development and delivery, from molecular modeling to combinatorial chemistry, from target validation to lead generation and ADMET studies. ChemMedChem typically covers topics on small molecules, therapeutic macromolecules, peptides, peptidomimetics, and aptamers, protein-drug conjugates, nucleic acid therapies, and beginning 2017, nanomedicine, particularly 1) targeted nanodelivery, 2) theranostic nanoparticles, and 3) nanodrugs. Contents ChemMedChem publishes an attractive mixture of: Full Papers and Communications Reviews and Minireviews Patent Reviews Highlights and Concepts Book and Multimedia Reviews.
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