Immobilization of RAFT-Derived Periodic Glycopolymers on Gold Surfaces for Quantitative Glycan–Protein Interaction Analysis

To understand glycan–protein interactions at biological interfaces, designing surfaces modified with structurally controlled glycans is highly important. In particular, naturally occurring glycosaminoglycans (GAGs) possess periodic sugar arrangements that play important roles in protein recognition, highlighting the need for the development of periodic glycopolymer model systems that can serve as GAG mimics for quantitative interaction analysis. In this study, sequence-controlled periodic glycopolymers were synthesized by reversible addition–fragmentation chain-transfer (RAFT) polymerization and immobilized onto gold surfaces to construct glycan-modified interfaces. The synthesized material was a terminally functionalized periodic glycopolymer with the most basic structure, consisting of alternating maltose-containing vinyl ether (MalVE) units and ethyl maleimide (EtMI) units, with a trithiocarbonate group at the ω-terminal. This trithiocarbonate group was converted to a thiol group for immobilization through Au–S bond formation. Structural characterization by 1H NMR spectroscopy, size exclusion chromatography (SEC), MALDI-TOF mass spectrometry, and UV–vis spectroscopy confirmed the structure as designed. Quartz crystal microbalance (QCM) measurements verified the stable immobilization of thiol-terminated periodic glycopolymers on the gold surface, and allowed for estimation of graft density and quantitative analysis of glycan-protein interactions at the modified interface. The periodic glycopolymer-modified surfaces exhibited selective binding behavior toward concanavalin A (ConA) compared to bovine serum albumin (BSA), with apparent binding constants on the order of 106–107 L mol−1. This enhanced binding behavior indicated that specific and multivalent interactions with proteins also occurred at periodic pendant maltose residues along the main chain. These results demonstrate that the gold surface modified with end-functional periodic glycopolymers synthesized by RAFT polymerization provides a versatile platform for quantitative analysis of glycan-protein interactions and suggests potential applications for periodic glycopolymers as functional materials.