Structures of peptide agonists for human protease activated receptor 2

Stoermer, Martin J., Flanagan, Bernadine, Beyer, Renée L., Madala, Praveen K. and Fairlie, David P. (2012) Structures of peptide agonists for human protease activated receptor 2. Bioorganic and Medicinal Chemistry Letters, 22 2: 916-919. doi:10.1016/j.bmcl.2011.12.029

Author Stoermer, Martin J.
Flanagan, Bernadine
Beyer, Renée L.
Madala, Praveen K.
Fairlie, David P.
Title Structures of peptide agonists for human protease activated receptor 2
Journal name Bioorganic and Medicinal Chemistry Letters   Check publisher's open access policy
ISSN 0960-894X
Publication date 2012-01-01
Year available 2011
Sub-type Article (original research)
DOI 10.1016/j.bmcl.2011.12.029
Open Access Status Not Open Access
Volume 22
Issue 2
Start page 916
End page 919
Total pages 4
Place of publication East Park, Kidlington, Oxford, U.K.
Publisher Pergamon
Language eng
Formatted abstract
Protease activated receptor 2 (PAR2) is an unusual G-protein coupled receptor in being self-activated, after pruning of the N-terminus by serine proteases like trypsin and tryptase. Short synthetic peptides corresponding to the newly exposed N-terminal hexapeptide sequence also activate PAR2 on immunoinflammatory, cancer and many normal cell types. 1H nuclear magnetic resonance (NMR) and circular dichroism (CD) spectroscopy were used here to search for structural clues to activating mechanisms of the hexapeptide agonists SLIGRL (rat), SLIGKV (human) and the peptidomimetic analogue, 2-furoyl-LIGRLO. Either with a free or acetyl capped N-terminus, these agonist peptides display significant propensity in aprotic (DMSO) or lipidic (water–SDS) solvents for turn-like conformations, which are predicted to be receptor-binding conformations in the transmembrane or loops region of PAR2. These motifs may be valuable for the design of small molecule PAR2 agonists and antagonists as prospective new drugs for regulating inflammatory and proliferative diseases.
Keyword Protease activated receptor 2
Circular dichroism
Molecular modeling
Thrombin receptor
Coupled receptors
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Available online 13 December 2011.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2012 Collection
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