Sequence-Controlled High Molecular Weight Glyco(oligoamide)–PEG Multiblock Copolymers as Ligands and Inhibitors in Lectin Binding

Abstract

A synthesis toward sequence-controlled multiblock glycopolymers, presenting a mannopyranoside (Man) glyco(oligoamide) block followed by a poly(ethylene glycol) (PEG) (M̅n of 6 kDa) block, is shown. Therefore, monodisperse and sequence-defined glyco(oligoamide) macromonomers derived from solid phase synthesis (SPS) are polymerized with dithiol-functionalized PEG via thiol–ene coupling (TEC) in a step-growth fashion. For the polymerization, a novel building block introducing a norbornene moiety is developed which is used for end-functionalization of the glyco(oligoamide) macromonomers. As a highly reactive alkene moiety in photoinduced TEC, this gives access to X̅n of up to 45. A total of 12 glyco(oligoamide)–PEG multiblock copolymers with maximum M̅n of 200 kDa are obtained and subjected to a series of purification steps decreasing overall dispersity. In different binding studies toward model lectin Concanavalin A, despite their high number of Man ligands, we see rather weak binding of glycopolymers that we attribute to the introduction of higher molecular weight PEG blocks.