Pentafluorophenyl ester-functionalized phosphorylcholine polymers: preparation of linear, two-arm, and grafted polymer-protein conjugates.
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.
Polymer Science & Engineering Department, University of Massachusetts, Amherst, Massachusetts 01003, United States.
Samantha
S
McRae
Xiangji
X
Chen
Katrina
K
Kratz
Debasis
D
Samanta
Elizabeth
E
Henchey
Sallie
S
Schneider
Todd
T
Emrick
D000818:Animals; D019540:Area Under Curve; D004795:Enzyme Stability; D004952:Esters; D005464:Fluorobenzenes / Q000737:chemistry*; D005465:Fluorocarbon Polymers / Q000138:chemical synthesis* / Q000737:chemistry; D006207:Half-Life; D051379:Mice; D008810:Mice, Inbred C57BL; D008837:Micrococcus / Q000737:chemistry; D008970:Molecular Weight; D009113:Muramidase / Q000737:chemistry* / Q000493:pharmacokinetics; D010316:Particle Size; D010767:Phosphorylcholine / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D058105:Polymerization
D004952:Esters; D005464:Fluorobenzenes; D005465:Fluorocarbon Polymers; D010767:Phosphorylcholine; D009113:Muramidase