Synthesis and biological characterization of human monocyte chemoattractant protein 1 (MCP-1) and its analogs

J Pept Sci. 2006 Jan;12(1):25-32. doi: 10.1002/psc.680.

Abstract

Novel analogs of human monocyte chemoattractant protein 1 (MCP-1) were designed, synthesized and characterized to be used as tools to generate monoclonal antibodies as potential human therapeutics. MCP-1 and three analogs were synthesized by step-wise Fmoc solid phase synthesis. After oxidation to form the two-disulfide bonds, affinity chromatography using an immobilized mouse anti-human MCP-1 monoclonal antibody (mAb) was utilized for a simple and highly effective purification procedure for the proteins. The final products were extensively characterized and compared with recombinant human MCP-1 (rhMCP-1). All proteins showed identical binding with mouse anti-human MCP-1 mAbs as measured by surface plasmon resonance. Synthetic MCP-1 and the analogs were comparable to recombinant MCP-1 in competition radio-ligand binding to CCR2 receptors on THP-1 cells, and MCP-1-induced, calcium mobilization and chemotaxis assays.

Publication types

  • Comparative Study

MeSH terms

  • Amino Acid Sequence
  • Antibodies, Monoclonal / chemistry
  • Antibodies, Monoclonal / pharmacology
  • Binding, Competitive
  • Calcium / metabolism
  • Cell Line
  • Chemokine CCL2 / chemical synthesis*
  • Chemokine CCL2 / chemistry
  • Chemokine CCL2 / pharmacology*
  • Chemotaxis / drug effects
  • Chemotaxis / physiology
  • Humans
  • Ligands
  • Molecular Sequence Data
  • Molecular Weight
  • Protein Binding
  • Receptors, CCR2
  • Receptors, Chemokine / drug effects
  • Structure-Activity Relationship

Substances

  • Antibodies, Monoclonal
  • CCL2 protein, human
  • CCR2 protein, human
  • Ccr2 protein, mouse
  • Chemokine CCL2
  • Ligands
  • Receptors, CCR2
  • Receptors, Chemokine
  • Calcium