化学
树枝状大分子
肽
分子内力
组合化学
圆二色性
侧链
立体化学
赖氨酸
计算生物学
生物化学
氨基酸
有机化学
聚合物
生物
作者
Xingguang Cai,Alice Capecchi,Basak Olcay,Markus Orsi,Sacha Javor,Jean‐Louis Reymond
标识
DOI:10.1002/ijch.202300096
摘要
Abstract There is an urgent need to develop new antibacterial agents against multidrug resistant bacteria. Herein we report our investigation of antimicrobial peptide dendrimers (AMPDs) active against Gram‐negative bacteria, whose sequences were designed using a genetic algorithm optimizing molecular similarity to the previously reported AMPD T7 with sequence (KL) 8 ( K KL) 4 ( K KLL) 2 K KKL. Our computational approach selected analogues unlikely to emerge from a systematic study, including AMPD X66 with a non‐conservative Leu→Glu mutation at the dendrimer core which proved compatible with antibacterial effects. Circular dichroism showed that this AMPD is α‐helical. Molecular dynamics suggest that its α‐helical structure is stabilized by an intramolecular salt bridge involving the core glutamate side chain and a lysine side chain in the dendrimer branches. More substantial variations at the dendrimer core were also tolerated such as the installation of the dianionic pegylated fatty acid side chain of the drug semaglutide potentially useful for in vivo studies.
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