Elucidating the Structural Requirement of Uridylpeptide Antibiotics for Antibacterial Activity
Elucidating the Structural Requirement of Uridylpeptide Antibiotics for Antibacterial Activity
复制标题
阐明尿苷肽抗生素抗菌活性的结构要求
DOI：
10.1021/acs.jmedchem.0c00973
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发表时间：
2020
期刊：
影响因子：
7.3
通讯作者：
and Satoshi Ichikawa
中科院分区：
文献类型：
--
作者：
Yuma Terasawa;Chisato Sataka;Toyotaka Sato;Kazuki Yamamoto;Yukari Fukushima;Chie Nakajima;Yasuhiko Suzuki;Akira Katsuyama;Takanori Matsumaru;Fumika Yakushiji;Shin-ichi Yokota;and Satoshi Ichikawa
The synthesis and biological evaluation of analogues of uridylpeptide antibiotics were described, and the molecular interaction between the 3′-hydroxy analogue of mureidomycin A (3′-hydroxymureidomycin A) and its target enzyme, phospho-MurNAc-pentapeptide transferase (MraY), was analyzed in detail. The structure–activity relationship (SAR) involving MraY inhibition suggests that the side chain at the urea-dipeptide moiety does not affect the MraY inhibition. However, the anti-Pseudomonas aeruginosaactivity is in great contrast and the urea-dipeptide motif is a key contributor. It is also suggested that the nucleoside peptide permease NppA1A2BCD is responsible for the transport of 3′-hydroxymureidomycin A into the cytoplasm. A systematic SAR analysis of the urea-dipeptide moiety of 3′-hydroxymureidomycin A was further conducted and the antibacterial activity was determined. This study provides a guide for the rational design of analogues based on uridylpeptide antibiotics.
