Rigidity vs Activity: Design of Gramicidin S Analogs against Multidrug-Resistant Bacteria Based on Molecular Engineering.

ABSTRACT: Antimicrobial peptides are a promising class of therapeutics to address antibiotic resistance; yet, their clinical use is limited by toxicity and narrow-spectrum activity. To better understand how conformational rigidity influences efficacy and safety, a series of β-sheet antimicrobial peptide analogs based on gramicidin S were designed and synthesized. Two stapled derivatives (GS_C-FB and GS_C-SS) and a flexible linear analog (GS-L) were prepared and evaluated. GS_C-FB retained potent activity against Gram-positive bacteria with a significantly reduced cytotoxicity. GS-L, characterized by increased conformational flexibility, showed broader-spectrum activity, including activity against Gram-negative strains, and similarly improved safety. Circular dichroism s

SUBMITTER: Sleziak M 

PROVIDER: S-EPMC12516685 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature