Thermoresponsive Miktoarm Glycopolymer–Protein Conjugates Based on Molecular Recognition: Synthesis and Self-Assembly

Simultaneously modifying proteins with different polymers can enrich protein functions and provide various polymer–protein conjugates. Investigating the self-assembly of complex amphiphilic polymer–protein conjugates offers insights into the formation of different protein structures. Herein, we synthesize a new bifunctional chain transfer agent with both an adamantyl group and a biotin group (AB-CTA) to prepare the thermoresponsive poly(di(ethylene glycol) methyl ether methacrylate) with the two functional groups (AB-PDEGMA). Two types of glycopolymers were synthesized and each was modified with a β-cyclodextrin (β-CD) group. AB-PDEGMA was mixed with the β-CD-modified glycopolymer, affording a block copolymer. It was then conjugated to streptavidin (SA) to prepare miktoarm glycopolymer–protein conjugates. The whole process is modularized based on molecular recognition of adamantane/β-CD and SA/biotin. It is accessible to adjust the polymer type and chain length to prepare the desired conjugates. Self-assembly of the miktoarm glycopolymer-SA conjugates was investigated above their lower critical solution temperatures. Assemblies including spherical micelles, compound micelles with patchy structures, and proteinosomes could be obtained. The influences of the binding number of the block copolymer and PDEGMA chain length on self-assembly were revealed, which was consistent with conclusions reported in previous simulation articles.