Synthesis of well-defined heteroglycopolymers via combining sequential click reactions and PPM: the effects of linker and heterogeneity on Con A binding?

Polymer Chemistry Pub Date: 2020-03-31 DOI: 10.1039/D0PY00302F

Abstract

Heteroglycopolymers displaying different sugar motifs have been increasingly used as tools to investigate the inherent heterogeneity in carbohydrate–protein binding to date. However, the fabrication of well-defined heteroglycopolymers still remains a challenge for chemists. Herein a library of well-defined homo and hetero-glycopolymers consisting of different sugar units in the side chain were generated by reacting poly(pentafluorophenyl acrylate) (pPFPA) with difunctionalized sugar amines via post-polymerization modification, in which one class of sugar motifs is linked by the flexible thiol ether bond while the same or different sugar motifs are connected by the rigid triazole ring in the side chain. A series of difunctionalized sugar amines were synthesized by implementing sequential CuAAC and thiol–ene click reactions, which could serve as a facile methodology for achieving heterogeneous sugar synthetic blocks with functional control. Isothermal titration calorimetry (ITC) measurements of the obtained glycopolymers with concanavalin A (Con A) as the model receptor indicated that heterogeneous glycopolymers bearing binding units α-D-mannose and non-binding sugar motifs in the side chains show higher affinities to Con A as compared to monoglycopolymer P(αManN-ene) in which the non-binding sugar motif was substituted with a non-sugar unit. We hypothesized that this may be due to the presence of β-glucose and β-galactose units as secondary sugar units producing a synergistic effect for the binding of α-mannose units to Con A. More surprisingly, heterogeneous glycopolymers in which α-D-mannose is linked by the flexible thiol ether bond in the side chain showed higher binding affinity to Con A in comparison with the heterogeneous glycopolymers in which α-D-mannose is linked by the rigid triazole ring since the flexible linker could provide more spaces on the polymer chain to bind Con A.

Graphical abstract: Synthesis of well-defined heteroglycopolymers via combining sequential click reactions and PPM: the effects of linker and heterogeneity on Con A binding
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