Glycopolymer–peptide bioconjugates with antioxidant activity via RAFT polymerization

Abstract

Well-defined protected glycopolymer poly(2-(2,3,4,6-tetra-O-acetyl-β-D-glucosyloxy)ethyl methacrylate) (PAcGlcEMA) is synthesized by reversible addition–fragmentation chain transfer (RAFT) radical polymerization. In the presence of ethanolamine and 2,2′-dithiodipyridine, PAcGlcEMA-PDS with end thiol-reactive pyridyldisulfide (PDS) group is generated by a one-pot approach. After deprotection of PAcGlcEMA, tripeptide reduced glutathione (GSH) is conjugated to PGlcEMA-PDS by thiol–disulfide exchange reaction under mild conditions. Fluorescent assay and TEM studies demonstrate that the pendant glucose residues on PGlcEMA have specific recognition with protein Concanavalin A (Con A). In comparison to PGlcEMA-PDS, the bioconjugation of GSH to PGlcEMA enhances the affinity of glycopolymer to Con A. The association constant (Ka) for the interaction of PGlcEMA-GSH bioconjugate and Con A is 6.1 × 103 M−1, displaying a high glycoside cluster effect. The disulfide-linked GSH bioconjugate PGlcEMA-GSH shows antioxidant activity. The radical scavenging activity is validated in vitro by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. It is found that the scavenging activity is dependent on reaction time and temperature. A sustained radical scavenging activity is observed at 37 °C, and about 50% DPPH radical is cleared after 24 h incubation. The recognition and the antioxidant activity make the peptide–glycopolymer bioconjugate PGlcEMA-GSH have potential for biodetection, biomimetics and targeted antioxidant delivery.