A refined agonist pharmacophore for protease activated receptor 2

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.