A refined agonist pharmacophore for protease activated receptor 2.
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.
Barry
Grant D
GD
Centre for Drug Design and Development, Institute for Molecular Bioscience, University of Queensland, Brisbane, Qld. 4072, Australia.
Suen
Jacky Y
JY
Low
Heng Boon
HB
Pfeiffer
Bernhard
B
Flanagan
Bernadine
B
Halili
Maria
M
Le
Giang T
GT
Fairlie
David P
DP
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
D010455:Peptides; D044464:Receptor, PAR-2; D002118:Calcium