Segment-Based Peptide Design Reveals the Importance of N-Terminal High Cationicity for Antimicrobial Activity Against Gram-Negative Pathogens.

ABSTRACT: Host defense antimicrobial peptides (AMPs) are recognized candidates to develop a new generation of peptide antibiotics. While high hydrophobicity can be deployed in peptides for eliminating Gram-positive bacteria, high cationicity is usually observed in AMPs against Gram-negative pathogen. This study investigates how the sequence distribution of basic amino acids affects peptide activity. For this purpose, we utilized human cathelicidin LL-37 as a template and designed four highly selective ultrashort peptides with similar length, net charge, and hydrophobic content. LL-10 + , RK-9 + , KR-8 + , and RIK-10 + showed similar activity against methicillin-resistant Staphylococcus aureus in vitro and comparable antibiofilm efficacy in a murine wound model. However, these peptides showed clear a

SUBMITTER: Mechesso AF 

PROVIDER: S-EPMC12744306 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature