Designing a leucine‐rich antibacterial nonapeptide with potent activity against mupirocin‐resistant MRSA via a structure–activity relationship study. (5th April 2021)

• Record Type: Journal Article
• Authors: Ang, Qi An; Arfan, Giovinna; Ong, Chu Yang Fann; Ng, Fui Mee; Ong, Esther H. Q.; Chia, Cheng San Brian
• Is Part Of: Chemical biology & drug design. Volume 97:Number 6(2021)
• Page Start: 1185
• Page End: 1193
• Publication Date: 2021-04-05
• Subjects: antibacterial peptide -- antimicrobial peptide -- MRSA -- mupirocin -- skin infection -- topical antibiotic; Drugs -- Design -- Periodicals; Pharmaceutical chemistry -- Periodicals; Biochemistry -- Periodicals; 615.19005
• DOI: 10.1111/cbdd.13840
• Languages: English
• ISSNs: 1747-0277

Abstract

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. Abstract : A potent anti‐MRSA 9‐residue linear peptide consisting of only two lysines and seven leucines was designed using a structure–activity relationship study with potential for treating skin infections caused by mupirocin‐resistant MRSA.