Covalent conjugation of cationic antimicrobial peptides with a β-lactam antibiotic core

Abstract

To combat the serious issue of increasing global antibiotic resistance, new antimicrobial therapies are urgently required. As one alternative, previously used antibiotics are being investigated for use in combination with more modern antibiotics including antimicrobial peptides. Towards this goal, 7-aminocephalosporanic acid, the precursor to the conventional β-lactam antibiotic, cephalosporin, and the related compound, 7-aminodesacetoxycephalosporanic acid, were each chemically modified to enable their use in solid phase peptide synthesis for covalent conjugation via their 7-amino group and a glycolic linker to the N-terminus of a series of cationic antimicrobial peptides, MSI-78, CA(1-7)M(..