Identification of novel peptide agonists from a random peptide library for a 5-oxo-ETE receptor, a receptor for bioactive lipids

✍ Scribed by Yoshinori Sasaki; Takashi Tsujii; Shigeki Takeda; Hideru Obinata; Takashi Izumi; Keiichi Yamada; Ryoichi Katakai

• Publisher: John Wiley and Sons
• Year: 2008
• Tongue: English
• Weight: 168 KB
• Volume: 14
• Category: Article
• ISSN: 1075-2617
• DOI: 10.1002/psc.1064

✦ Synopsis

Abstract

A combinatorial peptide library contains an enormous combination of amino acid sequences and drug candidates, but an effective screening strategy to identify a variety of bioactive peptides has yet to be established. In this article, a random hexapeptide library was screened to identify novel peptide ligands for a 5‐oxo‐ETE receptor (OXER), which is a G‐protein‐coupled receptor for bioactive lipids, by using an OXER‐Gi1α fusion protein. We successfully identified 2 hexapeptides—Ac‐HMQLYF‐NH~2~ and Ac‐HMWLYF‐NH~2~—that exhibited agonistic activity. Although the corresponding affinities were relatively low (EC~50~ values of 146 and 6.7 µM, respectively), the activities were confirmed by other independent cell‐based assay methods, namely, intracellular calcium mobilization and cell chemotaxis. This study demonstrates that a combinatorial peptide library may be screened using a [^35^S]GTPγS binding assay with G‐protein‐coupled receptor (GPCR)–Gα fusion proteins, in general, and that of peptide ligands can be obtained even for nonpeptide receptors. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.