Pentafluorophenyl Ester-Functionalized Phosphorylcholine Polymers: Preparation of Linear, Two-Arm, and Grafted Polymer鈥揚rotein Conjugates
文摘
Novel pentafluorophenyl (PFP)-ester-functionalized phosphorylcholine (PC) polymers of different architectures were prepared and conjugated to lysozyme as a model protein. Linear and two-arm poly(2-methacryloyloxyethyl phosphorylcholine) (polyMPC) structures containing PFP functionality at the chain-end were prepared by atom transfer radical polymerization (ATRP) from novel initiators. Additional conjugates were prepared from phosphorylcholine-substituted cyclooctene (PC-COE) polymers containing PFP-ester bearing comonomers. The polymer鈥損rotein conjugates were characterized by HPLC, FPLC, and DLS and were seen to retain most (80% or greater) of their native enzymatic activity. Pharmacokinetic profiles of the polymer鈥損rotein conjugates were studied in mice and found to increase the circulation half-life compared with lysozyme alone.