Cationic antimicrobial peptides (AMPs) possess direct bactericidal mechanism with minimal risk of inducing drug resistance and detrimental toxicity towards blood and mammalian cells. The cationic AMP HHC10 with cysteine terminal (CysHHC10) was conjugated via thiol-yne ‘click’ reaction onto the polyphosphoesters with alkynyl moieties, prepared by ring-opening polymerization (ROP) of cyclic dioxaphospholanes. On peptide mass-fraction basis, the polyphosphoester-peptide conjugates showed enhanced bactericidal efficacy with reduced hemolytic activity and cytotoxicity in comparison to the free peptide. Propargyl-terminated α-polylysine, prepared by N-carboxyanhydride ROP, was conjugated via ‘click’ cycloaddition onto the azido-terminated mannose, glucose, and galactose-based glycopolymers prepared by atom-transfer radical polymerization (ATRP). The resulting four-arm star glycopolymers-polypeptide conjugates were non-hemolytic and enhanced the cytocompatibility of linear α-polylysine without losing the bactericidal properties. In particular, the pendant mannose moieties of the star copolymers facilitated microbial targeting through molecular recognition and specific affinity with bacterial surfaces. CysHHC10 was also conjugated via thiol-maleimide ‘click’ reaction to maleimido-functionalized chitosan on the amino-C2 position or hydroxyl-C6 position. On peptide mass-fraction basis, the resulting peptido-polysaccharides inhibited bacteria growth and reduced cytotoxicity of the free peptide. Antibacterial coatings were readily constructed via layer-by-layer assembly of these peptido-polysaccharides with tannic acid through Michael addition or Schiff base reactions. The peptido-polysaccharide coatings immediately eliminated the adhered bacteria while still facilitated adhesion and proliferation of fibroblasts.

Cationic poly(peptidophosphoesters) and poly(peptidosaccharides) for antimicrobial therapy

255th National Meeting (2018)

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.