A refined agonist pharmacophore for protease activated receptor 2

Bioorg Med Chem Lett. 2007 Oct 15;17(20):5552-7. doi: 10.1016/j.bmcl.2007.08.026. Epub 2007 Aug 16.

Abstract

Protease activated receptor 2 (PAR(2)) is a G protein-coupled receptor implicated in inflammation and cancer. Only a few peptide agonists are known with greater potency than the native agonist SLIGRL-NH(2). Here we report 52 peptide agonists of PAR(2), 26 with activity at sub-micromolar concentrations, and one being iodinated for radioligand experiments. Potency was highest when the N- or C-termini of SLIGRL-NH(2) were modified, pointing to a new ligand pharmacophore model that may aid development of drug-like PAR(2) modulators.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amination
  • Calcium / metabolism
  • Cell Line
  • Humans
  • Molecular Structure
  • Peptides / chemistry
  • Peptides / pharmacology
  • Receptor, PAR-2 / agonists*
  • Receptor, PAR-2 / metabolism*
  • Structure-Activity Relationship

Substances

  • Peptides
  • Receptor, PAR-2
  • Calcium