title: 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.
authors.affiliation: Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld. 4072, Australia.
authors.forename: Grant D
authors.initials: GD
authors.lastname: Barry
authors.forename: Jacky Y
authors.initials: JY
authors.lastname: Suen
authors.forename: Heng Boon
authors.initials: HB
authors.lastname: Low
authors.forename: Bernhard
authors.initials: B
authors.lastname: Pfeiffer
authors.forename: Bernadine
authors.initials: B
authors.lastname: Flanagan
authors.forename: Maria
authors.initials: M
authors.lastname: Halili
authors.forename: Giang T
authors.initials: GT
authors.lastname: Le
authors.forename: David P
authors.initials: DP
authors.lastname: Fairlie
mesh_terms: D000586:Amination; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006801:Humans; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology; D044464:Receptor, PAR-2 / Q000819:agonists* / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D044464:Receptor, PAR-2; D002118:Calcium