1. Identification of novel peptide agonists from a random peptide library for a 5-oxo-ETE receptor, a receptor for bioactive lipids.
- Author
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Sasaki Y, Tsujii T, Takeda S, Obinata H, Izumi T, Yamada K, and Katakai R
- Subjects
- Ligands, Lipids chemistry, Peptides chemical synthesis, Peptides chemistry, Receptors, Eicosanoid chemistry, Receptors, Eicosanoid metabolism, Receptors, G-Protein-Coupled agonists, Receptors, G-Protein-Coupled metabolism, Peptide Library, Peptides pharmacology, Receptors, Eicosanoid agonists
- 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-Gi1alpha fusion protein. We successfully identified 2 hexapeptides-Ac-HMQLYF-NH2 and Ac-HMWLYF-NH(2)-that exhibited agonistic activity. Although the corresponding affinities were relatively low (EC50 values of 146 and 6.7 microM, 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 [35S]GTPgammaS binding assay with G-protein-coupled receptor (GPCR)-Galpha 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.)
- Published
- 2008
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