Structure-Based Rational Design of Small α-Helical Peptides with Broad-Spectrum Activity against Multidrug-Resistant Pathogens.

ABSTRACT: A series of small (7-12 mer) amphipathic cationic peptides were designed and synthesized to create short helical peptides with broad-range bactericidal activity and selectivity toward the bacterial cells. The analysis identified a lead 12-mer peptide 8b with broad-spectrum activity against Gram-positive (MIC = 3.1-6.2 μg/mL) and Gram-negative (MIC = 6.2-12.5 μg/mL) bacteria and selectivity toward prokaryotic versus eukaryotic cells (HC₅₀ = 280 μg/mL, >75% cell viability at 150 μg/mL). The rapid membranolytic action of 8b was demonstrated by a calcein dye leakage assay and confirmed using scanning electron microscopy. According to circular dichroism and NMR spectroscopy, the peptides have an irregular spatial structure in water. A lipid bilayer induced an amphipathi

SUBMITTER: Lohan S 

PROVIDER: S-EPMC9841524 | biostudies-literature | 2023 Jan

REPOSITORIES: biostudies-literature