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

We report the successful conjugation of a bioactive thiolated alpha(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.