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发现新型基于β-转角模拟肽的革兰氏阴性菌群体感应抑制剂。

Discovery of novel β-turn mimetic-based peptides as novel quorum sensing inhibitors of gram-negative bacteria.

机构信息

Faculty of Pharmacy, PHENIKAA University, Hanoi 12116, Viet Nam; PHENIKAA Institute for Advanced Study (PIAS), PHENIKAA University, Hanoi 12116, Viet Nam.

Nuclear Medicine Unit, Vinmec International Hospital, Hanoi 10000, Viet Nam.

出版信息

Bioorg Med Chem Lett. 2021 Aug 15;46:128170. doi: 10.1016/j.bmcl.2021.128170. Epub 2021 Jun 4.

Abstract

To date, a very limited number of peptides reported as quorum sensing inhibitors. Herein, we report the synthesis and evaluation of a series of β-turn mimetic-based peptides as potent quorum sensing inhibitors and antibiofilm formation. In this series, peptides P1, P4, and P5 showed very promising anti-quorum sensing activity on lasB-gfp reporter strain of Pseudomonas aeruginosa without affecting bacterial growth. Under our condition, these compounds also showed good anti-violacein production of Chromobacterium violaceum. In terms of antibiofilm formation, except P5, two β-turn mimetic-based peptides P1 and P4 showed maximum inhibition of 80% total biomass of Pseudomonas aeruginosa. This report provides the first β-turn mimetic-based scaffold for future drug development.

摘要

迄今为止,已报道的作为群体感应抑制剂的肽非常有限。本文报道了一系列基于β-转角模拟肽的合成和评估,这些肽作为有效的群体感应抑制剂和抗生物膜形成。在该系列中,肽 P1、P4 和 P5 对铜绿假单胞菌的 lasB-gfp 报告菌株表现出非常有前途的抗群体感应活性,而不影响细菌生长。在我们的条件下,这些化合物还显示出对变色杆菌生物膜形成的良好抑制作用。在抗生物膜形成方面,除 P5 外,两种基于β-转角模拟肽的肽 P1 和 P4 对铜绿假单胞菌的总生物量表现出最大 80%的抑制作用。本报告为未来的药物开发提供了第一个基于β-转角模拟物的支架。

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