Pentafluorophenyl ester-functionalized phosphorylcholine polymers: preparation of linear, two-arm, and grafted polymer-protein conjugates

Biomacromolecules. 2012 Jul 9;13(7):2099-109. doi: 10.1021/bm3004836. Epub 2012 Jun 12.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Area Under Curve
  • Enzyme Stability
  • Esters
  • Fluorobenzenes / chemistry*
  • Fluorocarbon Polymers / chemical synthesis*
  • Fluorocarbon Polymers / chemistry
  • Half-Life
  • Mice
  • Mice, Inbred C57BL
  • Micrococcus / chemistry
  • Molecular Weight
  • Muramidase / chemistry*
  • Muramidase / pharmacokinetics
  • Particle Size
  • Phosphorylcholine / analogs & derivatives*
  • Phosphorylcholine / chemical synthesis*
  • Phosphorylcholine / chemistry
  • Polymerization

Substances

  • Esters
  • Fluorobenzenes
  • Fluorocarbon Polymers
  • Phosphorylcholine
  • Muramidase