Polymer–trimannoside conjugates via a combination of RAFT and thiol–ene chemistry

Abstract

We report the successful conjugation of a bioactive thiolated α(1,2)-trimannoside to a copolymer of allyl methacrylate (AMA) and N-(2-hydroxypropyl) methacrylamide (HPMA) via photo-mediated thiol–ene chemistry. Well-defined copolymers of AMA and HPMA were synthesized by reversible addition–fragmentation chain transfer (RAFT) polymerization. Trimannose conjugation was carried out using near stoichiometric ratios of thiolated trimannoside to pendant alkene functional groups contained within the copolymer. About 87% disappearance of the alkene groups was observed in 2 h by proton NMR spectroscopy with approximately 9 trimannose units grafted per polymer chain. The glycan-modified polymer showed binding activity against the mannose-specific lectin concanavalin A, as observed by UV-Vis spectroscopy agglutination and surface plasmon resonance imaging (SPRi) analysis. These results demonstrate the facile addition of multivalent glycan targeting moieties to polymeric carrier segments.