Polymer Science & Engineering Department, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Biomacromolecules. 2012 Jul 9;13(7):2099-109. doi: 10.1021/bm3004836. Epub 2012 Jun 12.
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-protein 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-protein conjugates were studied in mice and found to increase the circulation half-life compared with lysozyme alone.
新型五氟苯基（PFP）酯官能化的不同结构的磷酸胆碱（PC）聚合物被制备出来，并与溶菌酶作为模型蛋白连接。通过原子转移自由基聚合（ATRP）从新型引发剂制备了具有链末端 PFP 官能团的线性和双臂聚（2-甲基丙烯酰氧基乙基磷酸胆碱）（polyMPC）结构。通过含有 PFP-酯基的共聚单体的磷酸胆碱取代环辛烯（PC-COE）聚合物制备了其他缀合物。聚合物-蛋白缀合物通过 HPLC、FPLC 和 DLS 进行了表征，并且保留了大部分（>80%）的天然酶活性。在小鼠中研究了聚合物-蛋白缀合物的药代动力学特征，发现与单独的溶菌酶相比，其循环半衰期增加。
