Fecha de publicación: -- Fuente: PubMed "microbial biotechnology" J Membr Biol. 2026 Nov 9;259(1):42. doi: 10.1007/s00232-026-00407-1.ABSTRACTThe selective activity of antimicrobial peptides (AMPs) against Gram-positive and Gram-negative bacteria is largely determined by their interactions with bacterial membranes. Consequently, elucidating the structural factors that govern membrane recognition and bacterial selectivity remains an important goal in AMPs design. Here, Mastoparan AF (MAF) and a series of derivatives were used to investigate how hydrophobicity, charge, and amphipathic topology influence antibacterial activity. A single alanine-to-leucine substitution increased peptide hydrophobicity and shifted antibacterial selectivity, enhancing activity against Gram-positive bacteria while reducing potency against Gram-negative species. In contrast, increasing net charge or disrupting the hydrophobic face markedly reduced antibacterial activity, highlighting the importance of maintaining an appropriate balance between charge and hydrophobicity. Molecular dynamics simulations revealed distinct membrane interaction patterns, with MAF interacting more extensively with Gram-positive membranes, whereas both peptides remained largely confined to the lipopolysaccharide-rich outer membrane of Gram-negative bacteria. These findings demonstrate that subtle changes in hydrophobicity can substantially alter membrane recognition and redirect antibacterial selectivity, providing insights into the rational design of membrane-active AMPs.PMID:43002252 | DOI:10.1007/s00232-026-00407-1