Aminooxy End-Functionalized Polymers Synthesized by ATRP for Chemoselective Conjugation to Proteins

Chemoselective oxime formation between aminooxy end-functional polymers and levulinyl-modified proteins is an attractive method to prepare well-defined bioconjugates. We demonstrate the synthesis of Boc-protected aminooxy initiators for atom transfer radical polymerization (ATRP) of acrylamide and methacrylate monomers. Copper-mediated ATRP of N- isopropylacrylamide (NIPAAm), 2-hydroxyethyl methacrylate (HEMA), and poly(ethylene glycol) methacrylate (PEGMA) resulted in polymers with polydispersity indices (PDIs) as low as 1.11, 1.18, and 1.24, respectively. Kinetic analysis indicated that ATRP of HEMA was well-controlled. The polymer end groups of polyNIPAAm were deprotected with trifluoroacetic acid, exposing α-aminooxy moieties. Complete removal of the Boc groups was confirmed by 1 H NMR, and the ability to form oxime bonds was verified by conjugation to aldehyde fluorescent nanospheres. Chemospecific reaction with N ε -levulinyl lysine-modified bovine serum albumin (BSA) to form “smart” polymer conjugates was demonstrated.