Squaric acid mediated bioconjugation expanded to polymers prepared by ATRP

The squaric acid mediated bioconjugation reaction is an attractive approach for the amine-selective protein modification with side-chain functional polymers. This manuscript presents 3 squaric acid based atom transfer radical polymerization (ATRP) initiators that significantly expand the scope of this bioconjugation reaction to a broad range of synthetic polymers that can be prepared by ATRP. Two proof-of-principle studies are discussed that demonstrate the feasibility of these novel initiators for the preparation of protein-synthetic polymer conjugates via both the grafting-onto as well as the grafting-from strategy. ATRP of polyethylene glycol methacrylate (PEGMA) with these initiators was used to generate a library of linear, mid-functional and 3-arm squaric acid functionalized PPEGMA derivatives. These PPEGMA polymers could subsequently be grafted onto bovine serum albumin (BSA), which was selected as a model protein. Alternatively, BSA could also be modified with these squaric acid based initiators to afford protein macroinitiators, which were successfully used to mediate ATRP of PEGMA and generate BSA-PPEGMA conjugates in a grafting-from process. This journal is