Well-defined temperature-responsive polymers were covalently conjugated to model proteins by two consecutive Michael additionthiol–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.
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