Conjugation of RAFT-generated polymers to proteins by two consecutive thiol–ene reactions

Abstract

Well-defined temperature-responsive polymers were covalently conjugated to model proteins by two consecutive Michael addition thiol–ene reactions. Poly(N-isopropylacrylamide) (PNIPAM) prepared by reversible addition–fragmentation chain transfer (RAFT) polymerization was aminolyzed to yield thiol-terminated chains that were subsequently reacted with excess 1,8-bis-maleimidodiethyleneglycol. The resulting maleimide-terminated polymer was reacted with bovine serum albumin and ovalbumin to yield polymer–protein conjugates by a “grafting-to” approach. The thermoresponsive nature of PNIPAM was conferred to the conjugate, as demonstrated by dynamic light scattering analysis that indicated the formation of intermolecular aggregates at elevated temperatures.