Synthesis of end-functionalized boronic acid containing copolymers and their bioconjugates with rod-like viruses for multiple responsive hydrogels

Abstract

When smart or responsive polymers are conjugated to biomolecules such as peptides or proteins, the resulting bioconjugates combine both bioactivities of the biomolecules and the responsive properties of the synthetic polymers. Among the responsive polymers, those containing boronic acid or its derivatives are unique due to their affinity to diol-containing compounds and pH dependent amphiphilicity. However, boronic acid containing polymer-based bioconjugates are rare, probably due to the challenges faced in the preparation of such bioconjugates. In this work, we report the synthesis of boronic acid containing polymers with an N-hydroxysuccinidic ester end functional group that can react with amino groups of a protein or peptide. Using a natural protein assembly rod-like M13 virus as a model, we demonstrate the preparation of boronic acid containing polymer–protein bioconjugates. Such virus–polymer bioconjugates can reversibly form hydrogels and the gelation behavior can be regulated by temperature, pH or diol-containing compounds such as glucose. Bioactive species can be loaded inside such hydrogel, and the glucose regulated insulin release is demonstrated under physiological conditions.