Selective Aza-Michael Addition to Dehydrated Amino Acids in Natural Antimicrobial Peptides

被引：0

作者：

Vargiu, Michela ^{[1
]}

Xu, Yanli ^{[2
]}

Kuipers, Oscar P. ^{[2
]}

Roelfes, Gerard ^{[1
]}

机构：

[1] Univ Groningen, Stratingh Inst Chem, Nijenborgh 4, NL-9747AG Groningen, Netherlands

[2] Univ Groningen, Groningen Biomol Sci & Biotechnol Inst, Dept Mol Genet, Nijenborgh 7, NL-9747AG Groningen, Netherlands

来源：

CHEMBIOCHEM | 2024年 / 25卷 / 07期

基金：

欧洲研究理事会;

关键词：

site-selective; antimicrobial peptides; Thiostrepton; Nisin; aza-michael; DEHYDROALANINE; BIOSYNTHESIS; THIOSTREPTON; DISCOVERY; PROTEINS;

D O I：

10.1002/cbic.202400043

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

We report the efficient and site selective modification of non-canonical dehydroamino acids in ribosomally synthesized and post-transationally modified peptides (RiPPs) by beta-amination. The singly modified thiopeptide Thiostrepton showed an up to 35-fold increase in water solubility, and minimum inhibitory concentration (MIC) assays showed that antimicrobial activity remained good, albeit lower than the unmodified peptide. Also the lanthipeptide nisin could be modified using this method. Antimicrobial resistance is an urgent global public health problem that has made the search for new antibiotics essential. Ribosomally synthesized and post-translationally modified peptides are a promising new class of antibiotics and in this work, we report site-selective modification of their dehydroamino acids by beta-amination in order to increase water solubility: the singly modified thiopeptide Thiostrepton showed an increase up to 35-fold and minimum inhibitory concentration tests demonstrated that the antimicrobial activity was still good, albeit lower than the natural peptide. image

引用

页数：5

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