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
Abstract
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.
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.
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