Structurally analogous trehalose and sucrose glycopolymers - comparative characterization and evaluation of their effects on insulin fibrillation

Recently, trehalose glycopolymers have been studied extensively in the context of various protein-related applications and have demonstrated some extraordinary properties. However, to fully verify their superior potential or elucidate the mechanism of their exceptional action, a relevant structural analogue is required for comparisons. The present study describes a method for synthesizing well-defined, highly structurally similar, and disaccharide-rich glycopolymers comprising trehalose and sucrose. Importantly, these glycopolymers are characterized by very low contents of non-saccharide structural fragments, which ensures that their properties are strongly dominated by the saccharide moieties. This report details the comprehensive comparative characterization of the glycopolymer analogues, including their tendency to self-assemble, their hydrolytic stabilities across a wide range of pH, and their potential susceptibilities to enzymatic hydrolysis by the corresponding glycosyl hydrolases. Additionally, the potential biorecognition of trehalose and sucrose glycopolymers through their terminal α- d -glucopyranosyl moieties is preliminarily assessed by testing their binding affinity toward the model lectin, Concanavalin A. Finally, the trehalose and sucrose glycopolymers are tested as inhibitors of amyloid fibrillogenesis, and their effects on human recombinant insulin fibrillation are thoroughly compared. This comparison reveals whether the inhibition activity is dependent on the disaccharide structure and whether trehalose glycopolymers exhibit any particularly superior anti-amyloidogenic properties. Comprehensive comparative characterization of highly structurally similar, RAFT-prepared trehalose and sucrose glycopolymers.