Cysteine-reactive polymers synthesized by atom transfer radical polymerization for conjugation to proteins

J Am Chem Soc. 2004 Dec 1;126(47):15372-3. doi: 10.1021/ja045063m.

Abstract

In this communication we report a strategy for the synthesis of semitelechelic polymers reactive to cysteines. An initiator modified with a pyridyl disulfide was prepared and used for the CuBr/2,2'-bipyridine-mediated atom transfer radical polymerization (ATRP) of 2-hydroxyethyl methacrylate. Polydispersity indices (M(w)/M(n)) of the polymers with different molecular weights were 1.25 or less. The pyridyl disulfide end group was preserved during the polymerization and allowed direct conjugation of the polymer to cysteine residues of bovine serum albumin. The described method provides a general way for the preparation of protein-polymer conjugates through a reversible disulfide bond without the need for postsynthesis modification of the polymers.

Publication types

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

MeSH terms

  • Cysteine / chemistry*
  • Disulfides / chemical synthesis
  • Disulfides / chemistry*
  • Dithiothreitol / chemistry
  • Kinetics
  • Polyamines / chemical synthesis
  • Polyamines / chemistry*
  • Polyhydroxyethyl Methacrylate / analogs & derivatives*
  • Polyhydroxyethyl Methacrylate / chemical synthesis
  • Polyhydroxyethyl Methacrylate / chemistry*
  • Serum Albumin, Bovine / chemistry*

Substances

  • Disulfides
  • Polyamines
  • poly(2-hydroxyethyl methacrylate)-polyamine graft copolymer
  • Polyhydroxyethyl Methacrylate
  • Serum Albumin, Bovine
  • Cysteine
  • Dithiothreitol