Synthesis of Protein–Polymer–Protein Bioconjugates by the Combination of Atom Transfer Radical Polymerization and Click Reaction

Novel protein–polymer–protein bioconjugates were synthesized by the successive reaction between both chain ends of a polymer and two different types of proteins. A poly(2‐(2‐methoxyethoxy)ethyl methacrylate) ( OH‐PMEO2MA ‐Br) was synthesized by atom transfer radical polymerization ( ATRP ) from a hydroxyl‐terminated initiator. The Br‐terminated chain ends of the resulting polymer in one end were transformed to azido groups ( OH‐PMEO2MA‐N 3 ) and subsequently the OH ‐terminated chain ends in the other end were transformed to 4‐nitrophenyl formate‐derivated group ( NPC‐PMEO2MA‐N 3 ). A model protein, cationized bovine serum albumin ( cBSA ) was reacted with 4‐nitrophenyl formate groups of NPC‐PMEO2MA‐N 3 to form cBSA‐PMEO2MA‐N 3 . The click reaction between azido‐terminated cBSA‐PMEO2MA‐N 3 and alkyne‐derived bovine serum albumin ( BSA alkyne ) yielded novel cBSA‐PMEO2MA‐BSA bioconjugates with two proteins at both polymer ends.