Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity

doi:10.1021/acs.jmedchem.4c01855

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	Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity
	Wu, Zhongxiang; Cai, Ying; Han, Yajun; Su, Yunhan; Zhang, Tianyu; Wang, Xingyu; Yan, An; Wang, Liunan; Wu, Sijing; Wang, Gan; Zhang, Zhiye
	2024
发表期刊	JOURNAL OF MEDICINAL CHEMISTRY
ISSN	0022-2623
卷号	67 期号:21 页码:19561-19572
摘要	The advancement of antimicrobial peptides (AMPs) as therapeutic agents is hindered by their poor selectivity. Recent evidence indicates that controlled disruption of the amphipathicity of alpha-helical AMPs may increase the selectivity. This study investigated the role of imperfect amphipathicity in optimizing AMPs with varied sequences to enhance their activity and selectivity. Among these, the lead peptide RI-18, characterized by an imperfectly amphipathic alpha-helical structure, demonstrated potent and broad-spectrum antibacterial activity without inducing hemolytic or cytotoxic effects. RI-18 effectively eliminated planktonic and biofilm-associated bacteria as well as persister cells and exhibited high bacterial plasma membrane affinity, inducing rapid membrane permeabilization and rupture. Notably, RI-18 significantly reduced bacterial loads without promoting bacterial resistance, highlighting its therapeutic potential. Overall, this study identified RI-18 as a promising antimicrobial candidate. The rational strategy of tuning imperfect amphipathicity to enhance the AMP activity and selectivity may facilitate the design and development of AMPs.
DOI	10.1021/acs.jmedchem.4c01855
WOS记录号	WOS:001346997700001
引用统计	被引频次：9[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/76017
专题	中国科学院昆明植物研究所
推荐引用方式 GB/T 7714	Wu, Zhongxiang,Cai, Ying,Han, Yajun,et al. Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity[J]. JOURNAL OF MEDICINAL CHEMISTRY,2024,67(21):19561-19572.
APA	Wu, Zhongxiang.,Cai, Ying.,Han, Yajun.,Su, Yunhan.,Zhang, Tianyu.,...&Zhang, Zhiye.(2024).Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity.JOURNAL OF MEDICINAL CHEMISTRY,67(21),19561-19572.
MLA	Wu, Zhongxiang,et al."Development of α-Helical Antimicrobial Peptides with Imperfect Amphipathicity for Superior Activity and Selectivity".JOURNAL OF MEDICINAL CHEMISTRY 67.21(2024):19561-19572.

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