From Polymer Sequence Control to Protein Recognition: Synthesis, Self-Assembly and Lectin Binding

Abstract

A novel, highly efficient methodology to synthesize gradient glycopolymers has been successfully developed involving concurrent enzymatic monomer transformation and reversible addition−fragmentation chain transfer (RAFT) polymerization. By synchronizing enzymatic monomer transformation with polymerization, a continuous supply of the second monomer (glycomonomer) is achieved during the polymerization, resulting in a gradient sugar distribution in the final polymer. Detailed studies of the process using GPC and NMR indicate that the gradient glycopolymers synthesized by RAFT were well controlled. Subsequently, 1,2:3,4-di-O-isopropylidene-6-O-methacryloyl-α-D-galactopyranose (DIMAG) moieties were deprotected to regenerate the sugar and achieve amphiphilic bioactive glycopolymers. We demonstrate the synthesis of a set of glycopolymers with different sequential structures, such as statistical, gradient and block glycopolymers. The glycopolymers with block structure show higher affinities toward the RCA 120 lectin receptor compared with other structural counterparts. Furthermore, simulation of the self-assembly of three types of copolymers and their binding to lectins provides fundamental insight into this result, revealing the mechanisms underlying the dependence of self-assembling structures and protein adsorption kinetics on the molecular architectures of copolymers.

Increasing bacterial affinity and cytocompatibility with four-arm star glycopolymers and antimicrobial α-polylysine

“…27,28 A library of galactosylated polymers with different statistical, gradient, and block microstructures were proven to have higher aptitude in clustering Ricinus communis (castor bean) agglutin RCA 120 than other glycopolymers. 29 Glycopeptide dendrimers based on galactose also showed high affinity to LecB and LecA lectins, and efficiently induced the biofilm dispersal of Pseudomonas aeruginosa. 30 It is thus a promising concept to employ glycopolymers in the design of antimicrobial compounds for modulating toxicity and simultaneously targeting bacterial cells.…”

Polymers for Fluorescence Imaging of Formaldehyde in Living Systems via the Hantzsch Reaction

“…[42][43][44][45][46][47][48][49][50][51][52][53][54][55] Recent studies have reported that polymer structures (i.e., sequences and topology structures) remarkably affect the properties or functions of polymers. 53,[56][57][58][59][60] Thus, the future combination of these modern CRP techniques with the method used herein might offer new polymeric probes for the more rapid, more precise detection of FA in biological systems.…”

New synthetic strategy for facile synthesis of functional polymers by one-pot combination of controlled radical polymerization and enzymatic reaction

“…An amphiphilic sugar‐containing gradient copolymer was further synthesized by employing protected galactose as alcohol substrate via this one‐pot method (Fig. ) . The influence of the macromolecular architecture, i.e.…”

“…One‐pot synthesis of gradient glycopolymer via concurrent enzymatic monomer transformation and RAFT polymerization and the effects of monomer sequence in the polymer on protein binding. Reproduced with permission . Copyright 2014, American Chemical Society.…”