The covalent attachment of polymers to the surface of proteins has become a fascinating topic of biomaterials research. Polymers can be used to tune the protein structure, functionality, and stability. Protein-polymer bioconjugate technologies have applications in catalysis, energy, medicine, and nanotechnology. Conjugates are typically synthesized by one of two approaches: grafting-to or grafting-from. The grafting-to approach involves synthesis of a polymer in a separate reaction, then covalent attachment to the protein. The second approach is the grafting-from approach, where an initiating group is attached to the protein, followed by the growth of polymer directly from the protein surface. While both techniques are useful, each has advantages and disadvantages. Notably, low attachment efficiency is a problem for grafting-to methods, while the grafting-from method may face protein stability and solubility challenges.<br/>We have previously developed a hybrid methodology which combines the advantages of high graft density when grafting-from, without sacrificing protein solubility and stability. In this strategy, short, water-soluble polymer chains were first synthesized then attached to the protein as in grafting-to; subsequently, the attached polymer chains were extended directly from the surface of the protein using a grafting-from technique. Reversible addition-fragmentation chain transfer (RAFT) polymerization was utilized to synthesize short polymers that were well-defined and contained various functional groups. Upon synthesis and characterization, the short polymers were covalently linked to the protein lysozyme which serves as a good model protein in these studies. The conjugate was characterized via MALDI-TOF mass spectrometry and enzyme activity assays, then chain extended with a variety of polymers of different functional groups and chain lengths. The bioconjugate and its chain-extended derivatives were subjected to further enzyme assays, chemical and thermal functional stability assays.<br/>This hybrid approach can be used to produce well-defined, protein-polymer bioconjugates with a variety of functional groups and polymer architectures. Understanding the effects of different functional groups, polymer architectures and chain length on the activity and stability of the bioconjugate can give structure-property correlations. These relationships can be used to engineer protein-polymer conjugates and tune their properties for various applications.

Tuning the activity and stability of protein-polymer conjugates by attaching functional polymers

251st National Meeting (2016)

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