Agonists and antagonists of protease activated receptors (PARs)

Barry, GD, Le, GT and Fairlie, DP (2006) Agonists and antagonists of protease activated receptors (PARs). Current Medicinal Chemistry, 13 3: 243-265. doi:10.2174/092986706775476070

Author Barry, GD
Le, GT
Fairlie, DP
Title Agonists and antagonists of protease activated receptors (PARs)
Journal name Current Medicinal Chemistry   Check publisher's open access policy
ISSN 0929-8673
Publication date 2006
Sub-type Critical review of research, literature review, critical commentary
DOI 10.2174/092986706775476070
Volume 13
Issue 3
Start page 243
End page 265
Total pages 23
Editor Atta-ur-Rahman
David Fairlie
William J. Hoekstra
Graeme Semple
Hakan V. Wikstrom
Place of publication The Netherlands
Publisher Bentham Science Publ Ltd
Collection year 2006
Language eng
Subject C1
320305 Medical Biochemistry - Proteins and Peptides
780103 Chemical sciences
Abstract Protease activated receptors (PARs) are a category of G-protein coupled receptors (GPCRs) implicated in the progression of a wide range of diseases, including thrombosis, inflammatory disorders, and proliferative diseases. Signal transduction via PARs proceeds via an unusual activation mechanism. Instead of being activated through direct interaction with an extracellular signal like most GPCRs. they are self-activated following cleavage of their extracellular N-terminus by serine proteases to generate a new receptor N-terminus that acts as an intramolecular ligand by folding back onto itself and triggering receptor activation. Short synthetic peptides corresponding to this newly exposed N-terminal tethered ligand can activate three of the four known PARs in the absence of proteases. and such PAR activating peptides (PAR-APs) have served as templates for agonist/antagonist development. In fact much of the evidence for involvement of PARs in diseases has relied upon use of PAR-APs. often of low potency and uncertain selectivity. This review summarizes current structures of PAR agonists and antagonists, the need for more selective and more potent PAR ligands that activate or antagonize this intriguing class of receptors, and outlines the background relevant to PAR activation, assay methods, and physiological properties anticipated for PAR ligands.
Keyword Gpcr
Biochemistry & Molecular Biology
Chemistry, Medicinal
Pharmacology & Pharmacy
Platelet Thrombin Receptor
Mast-cell Tryptase
Endothelium-dependent Relaxation
Neutrophil Serine Proteinases
Small-molecule Antagonist
Ligand-derived Peptides
Oral Epithelial-cells
Factor Xa
Q-Index Code C1
Additional Notes This document is a journal review.

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Excellence in Research Australia (ERA) - Collection
2007 Higher Education Research Data Collection
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 51 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 52 times in Scopus Article | Citations
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Created: Wed, 15 Aug 2007, 08:24:07 EST