Gramicidin‐S‐Inspired Cyclopeptidomimetics as Potent Membrane‐Active Bactericidal Agents with Therapeutic Potential. (16th October 2020)

• Record Type: Journal Article
• Authors: Hu, Chengfei; Wen, Quan; Huang, Shuhui; Xie, Saisai; Fang, Yuanying; Jin, Yi; Campagne, Rémy; Alezra, Valérie; Miclet, Emeric; Zhu, Jinhua; Wan, Yang
• Is Part Of: ChemMedChem. Volume 16:Number 2(2021)
• Page Start: 368
• Page End: 376
• Publication Date: 2020-10-16
• Subjects: peptidomimetics -- antibiotics -- membrane active -- hemolysis -- β, γ-diamino acids; Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.1002/cmdc.202000568
• Languages: English
• ISSNs: 1860-7179

Abstract

Abstract: 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. Abstract : Full circle : β, γ‐Diamino acids (β, γ‐DiAAs) were used as β‐strand inducers to synthesize gramicidin S (GS)‐inspired cyclopeptidomimetics. The resulting peptidomimetic CP‐2 displays an antibacterial activity comparable to that of GS and exerts a lower toxicity towards human cells. CP‐2 kills bacteria mainly through the disruption of cell membrane.