Increasing bacterial affinity and cytocompatibility with four arm star glycopolymers and antimicrobial a polylysine
A series of four arm star copolymers, incorporating glycopolymer and antimicrobial polypeptide domains, was developed in the design of forthcoming anti infective agents. Mannose, glucose, and galactose based glycopolymers with a variety of well defined chain lengths were prepared via atom transfer radical polymerization, whereas linear a polylysine was prepared via ring opening polymerization of N carboxyanhydride monomers. Copper catalyzed azide alkyne cycloaddition was employed for 'click' conjugation of the glycopolymer arms and the polypeptide chains. The glycopolymer polypeptide conjugates were non hemolytic and exhibited higher cytocompatibility than the linear a polylysine. The conjugates with shorter chains of mannose based glycopolymer arms showed an enhanced bactericidal efficacy against Gram negative and Gram positive bacteria, with a therapeutic selectivity half of that of the linear a polylysine. The pendant mannose moieties of the conjugates increased microbial targeting due to their specific affinity for bacterial surfaces, and binding competition with free mannopyranoside was demonstrated. Therefore, the molecular combination of glycopolymers and polypeptides without loss of their respective activities provides an interesting concept in the design of antimicrobial agents to combat infectious disease.