Selective Protein Conjugation of Poly(glycerol monomethacrylate) and Poly(polyethylene glycol methacrylate) with Tunable Topology via Reductive Amination with Multifunctional ATRP Initiators for Activity Preservation

In this study, we compare poly(glycerol monomethacrylate) (PGMA) of different chain lengths and architectures (linear and two-arm) with poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) as an alternative polymer platform for the synthesis of a new generation of protein-polymer conjugates. Mono-and two-arm functional atom-transfer radical polymerization (ATRP) initiators were designed and selectively attached to lysozyme at the N-terminus via reductive amination. Site-specific, grafting from activator regenerated by electron transfer (ARGET) ATRP was carried out in phosphate buffer, and the reaction parameters were optimized to obtain polymer conjugates with predetermined molar mass and topology. The activity preservation under proteolytic and high-temperature conditions showed a clear dependence on the structure of the repeating unit and on the macromolecular architecture. These results highlighted the potential of PGMA as a poly(ethylene glycol) (PEG) alternative for the half-life extension of biotherapeutics. Moreover, this synthetic approach may inspire the design of a new class of protein-polymer conjugates through an optimal combination of macromolecular composition and topology.

Automated summary

This study compares the performance of poly(glycerol monomethacrylate) (PGMA) and poly(poly(ethylene glycol) methyl ether methacrylate) (PPEGMA) as polymer platforms for protein-polymer conjugates. The results highlight the potential of PGMA as an alternative to poly(ethylene glycol) (PEG) for extending the half-life of biotherapeutics.