Glycine Substitution Reduces Antimicrobial Activity and Helical Stretch of diPGLa-H in Lipid Micelles

Abstract

With the rise in antibiotic resistance, antimicrobial peptides (AMPs) show promise for therapeutic development, but higher specificity is required. PGLa-H is a naturally occurring decapeptide, reported to have moderate antibacterial activity and low hemolytic activity, with its sequence being identical to that of the C-terminal fragment of highly selective AMP, PGLa. DiPGLa-H, a sequential tandem repeat of PGLa-H, and Kiadin, an analogue with a Val to Gly substitution at position 15, display improved in vitro bactericidal activity against both Gram-negative and Gram-positive pathogens, with generally low toxicity for human cells. Despite Gly being a more flexible residue, NMR structural stud..