Arginine-specific protein modification using alpha-oxo-aldehyde functional polymers prepared by atom transfer radical polymerization

The residue-specific modification of peptides and proteins is a powerful strategy for preparing biomolecular-synthetic polymer conjugates with advanced properties. This manuscript aims at expanding the present toolbox of residue-selective protein modification reactions and targets arginine, a residue for which selective polymer coupling chemistry has only recently been established. To this end, a protected, alpha-oxo-aldehyde functionalized ATRP initiator that can be used for the preparation of a variety of alpha-oxo-aldehyde functionalized polymethacrylates has been developed. Polymerization kinetics for four different methacrylate monomers have been investigated in detail and optimized conditions for the chain-end deprotection to reveal the alpha-oxo-aldehyde end-group have been elaborated. As a final proof of concept, the residue-specific modification of a model protein, chicken egg white lysozyme (HEWL), at arginine residues has been demonstrated.