Designing a leucine‐rich antibacterial nonapeptide with potent activity against mupirocin‐resistant MRSA via a structure–activity relationship study

Abstract

Staphylococcus aureus is the main aetiological agent responsible for the majority of human skin infections. Of particular concern is the methicillin‐resistant variety, commonly known as MRSA. The extensive use of the first‐line topical antibiotic of choice, mupirocin, has inevitably resulted in the emergence of resistant strains, signalling an urgent need for the development of new antibacterials with new mechanisms of action. In this work, we describe how we designed a novel cationic nonapeptide, containing only leucine and two lysine residues, with potent anti‐MRSA activity and a rapid bactericidal mode of action. Coupled to a favourable safety profile towards human skin fibroblasts, we believe nonapeptide 11 has high potential for further development as a mupirocin replacement candidate to treat skin infections caused by MRSA.

Evaluation of the Synthetic Multifunctional Peptide Hp-MAP3 Derivative of Temporin-PTa

“…Rational design can be used to modify the chemical and physical properties of existing peptides, thereby improving activity against targets or making them multifunctional for multiple targets [ 34 , 35 ]. Amphipathic peptides rich in lysines and leucines are multifunctional in various pathogenic cells [ 36 , 37 ]. Since these attributes are widely accepted for the design of synthetic AMPs.…”