Site-specific polymer attachment to a CCL-5 (RANTES) analogue by oxime exchange

J Am Chem Soc. 2005 Feb 9;127(5):1350-1. doi: 10.1021/ja043096w.


A synthetic strategy that allows for the site-specific attachment of polymers such as poly(ethylene glycol) (PEG) to protein pharmaceuticals is described. PEG was attached to a 67-amino acid fully synthetic CCL-5 (RANTES) analogue at its GAG binding site both to reduce aggregation and to increase the circulating lifetime. Effective protection of an Aoaa chemoselective linker during peptide assembly, total chemical protein synthesis, and protein folding was achieved with an isopropylidene group. Mild deprotection of the resulting folded synthetic protein and subsequent polymer attachment occur without interference with the native folded structure and activity.

MeSH terms

  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Binding Sites
  • Chemokine CCL5 / analogs & derivatives*
  • Chemokine CCL5 / chemistry
  • Chemokine CCL5 / pharmacology
  • Chemokines, CC / chemistry*
  • Chemokines, CC / pharmacology
  • Glycine / chemistry
  • HIV-1 / drug effects
  • Humans
  • Models, Molecular
  • Oximes / chemistry*
  • Polyethylene Glycols / chemistry
  • Protein Folding
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization


  • Anti-HIV Agents
  • CCL5 protein, human
  • Chemokine CCL5
  • Chemokines, CC
  • Oximes
  • Polyethylene Glycols
  • Glycine