Chemokine receptor-derived peptides as multi-target drug leads for the treatment of inflammatory diseases

Peptides. 2009 Jul;30(7):1296-305. doi: 10.1016/j.peptides.2009.03.016. Epub 2009 Apr 2.

Abstract

The rationale for multi-target drugs has been strengthened both on theoretical and empirical grounds. Serious diseases that are intractable to treatment were found to have multiple pathogenic factors and examples of successful drugs were shown to affect multiple disease targets. The salient features of multiple-target drugs, low target affinity and rapid binding kinetics, have been responsible for their late discovery and slow development. We predicted that peptides from the ligand-binding domains of chemokine (CK) receptors could be used to modulate the activities of disease-related chemokines (CKs) for therapeutic effect. We developed innovative technologies to produce, screen and optimize low affinity, chemokine-binding peptides (CBPs) derived from chemokine receptors (CRs). The peptides were found to have therapeutic activity in animal models of disease, confirming our prediction and validating the related technologies.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Chemokines / chemistry
  • Chemokines / metabolism
  • Drug Interactions
  • Female
  • Inflammation / drug therapy*
  • Mice
  • Molecular Sequence Data
  • Peptides / chemistry*
  • Peptides / genetics
  • Peptides / metabolism*
  • Peptides / therapeutic use*
  • Protein Binding
  • Receptors, Chemokine / chemistry*
  • Surface Plasmon Resonance

Substances

  • Chemokines
  • Peptides
  • Receptors, Chemokine