Design and synthesis of trivalent Tn glycoconjugate polymers by nitroxide-mediated polymerization

Abstract

A new synthetic method for preparing Tn glycoconjugate polymers, containing tumor-associated carbohydrate antigens, by controlled living radical polymerization is reported. To mimic the authentic structures of Tn glycopeptide antigens and to explore the controlled living radical polymerization, three tumor-associated carbohydrate antigens (GalNAc, GalNAcα1-O-Ser, and GalNAcα1-O-Thr) were attached to a styrene-type monomer through a diethylene glycol spacer. Under nitroxide-mediated polymerization, controlled living radical polymerization proceeded to afford defined glycopeptide polymers with different Tn densities and compositions. The polydispersity index (PDI) and molecular weights were increased and conversions were decreased upon increasing the concentration of Tn glycoconjugate monomers. The resulting Tn glycoconjugate polymers were characterized by NMR and IR. The spectral data indicate that the Tn glycoconjugate moiety did attach to the polymer chain and Tn glycoconjugate density could be adjusted through the nitroxide-mediated polymerization conditions. The number of Tn units containing in the polymer chains could be estimated by NMR integration. This synthetic approach provides a new and efficient tool for constructing novel Tn glycoconjugate polymers.