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Issue 31, 2015
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Polymer-protein conjugation via a ‘grafting to’ approach – a comparative study of the performance of protein-reactive RAFT chain transfer agents

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Abstract

Efficient polymer-protein conjugation is a crucial step in the design of many therapeutic protein formulations including nanoscopic vaccine formulations, antibody-drug conjugates and to enhance the in vivo behaviour of proteins. Here we aimed at preparing well-defined polymers for conjugation to proteins by reversible addition–fragmentation chain transfer (RAFT) polymerization of both acrylates and methacrylamides with protein-reactive chain transfer agents (CTAs). These RAFT agents contain either a N-hydroxysuccinimide (NHS) or pentafluorophenyl (PFP) ester moiety that can be conjugated to lysine residues, and alternatively a maleimide (MAL) or pyridyl disulfide (PDS) moiety that can be conjugated to cysteine residues. Efficiency of the bioconjugation of these polymers to bovine and avian serum albumin was investigated as a function of stoichiometry, polymer molecular weight and the presence of reducing agents. A large molar excess of polymer was required to obtain an acceptable degree of protein conjugation. However, protein modification with N-succinimidyl-S-acetylthiopropionate (SATP) to introduce sulfhydryl groups onto primary amines, significantly increased conjugation efficiency with MAL- and PDS-containing polymers.

Graphical abstract: Polymer-protein conjugation via a ‘grafting to’ approach – a comparative study of the performance of protein-reactive RAFT chain transfer agents

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Publication details

The article was received on 04 Sep 2014, accepted on 21 Oct 2014 and first published on 23 Oct 2014


Article type: Paper
DOI: 10.1039/C4PY01224K
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Citation: Polym. Chem., 2015,6, 5602-5614

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    Polymer-protein conjugation via a ‘grafting to’ approach – a comparative study of the performance of protein-reactive RAFT chain transfer agents

    N. Vanparijs, S. Maji, B. Louage, L. Voorhaar, D. Laplace, Q. Zhang, Y. Shi, W. E. Hennink, R. Hoogenboom and B. G. De Geest, Polym. Chem., 2015, 6, 5602
    DOI: 10.1039/C4PY01224K

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