Gramicidin‐S‐Inspired Cyclopeptidomimetics as Potent Membrane‐Active Bactericidal Agents with Therapeutic Potential

Chengfei Hu (1) , Quan Wen (2) , Shuhui Huang (3) , Saisai Xie (2) , Yuanying Fang (4) , Yi Jin (2) , Rémy Campagne (5) , Valérie Alezra (5) , Emeric Miclet (6, 7, 8, 9) , Jinhua Zhu (2) , Yang Wan (2)

1 Jiangxi University of Chinese Medicine
2 Jiangxi University of Traditional Chinese Medicine
3 Jiangxi Maternal and Child Hospital
4 College of Traditional Chinese Medicine, Jiangxi University of Traditional Chinese Medicine
5 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay
6 LBM UMR 7203 - Laboratoire des biomolécules
7 LBM-E3 - Structure et Dynamique des Biomolécules
8 SU - Sorbonne Université
9 UPMC - Université Pierre et Marie Curie - Paris 6

Antimicrobial peptides (AMPs) are promising antibacterial agents often hindered by their undesired hemolytic activity. Inspired by gramicidin S (GS), a well-known cyclodecapeptide, we synthesized a panel of antibacterial cyclopeptidomimetics using β,γ-diamino acids (β,γ-DiAAs). We observed that peptidomimetic CP-2 displays a bactericidal activity similar to that of GS while possessing lower side-effects. Moreover, extensive studies revealed that CP-2 likely kills bacteria through membrane disruption. Altogether, CP-2 is a promising membrane-active antibiotic with therapeutic potential

Mots clés: antibiotics; hemolysis; membrane active; peptidomimetics; β; γ-diamino acids

Domaines: Chimie

Chengfei Hu, Quan Wen, Shuhui Huang, Saisai Xie, Yuanying Fang, et al.. Gramicidin‐S‐Inspired Cyclopeptidomimetics as Potent Membrane‐Active Bactericidal Agents with Therapeutic Potential. ChemMedChem, 2021, 16 (2), pp.368-376. ⟨10.1002/cmdc.202000568⟩. ⟨hal-03988662⟩