In vitro selection of a peptide antagonist of growth hormone secretagogue receptor using cDNA display
| Autor: | Koichi Nishigaki, Anupom Mondal, Sayaka Yoshida, Makoto Koyama, Ichiro Sakata, Kazuya Nishina, Takafumi Sakai, Naoto Nemoto, Shingo Ueno, Kenju Miura, Yujiro Hayashi |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Male
DNA Complementary Growth hormone secretagogue receptor Peptide CHO Cells Pharmacology In Vitro Techniques Ligands Models Biological Polymerase Chain Reaction Inhibitory Concentration 50 Mice Cricetulus Complementary DNA Cricetinae Animals RNA Messenger Receptor Receptors Ghrelin G protein-coupled receptor Gene Library chemistry.chemical_classification Multidisciplinary biology Dose-Response Relationship Drug Biological Sciences biology.organism_classification In vitro Ghrelin chemistry Biochemistry Calcium Anti-Obesity Agents Peptides hormones hormone substitutes and hormone antagonists |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America. 109(28) |
| ISSN: | 1091-6490 |
| Popis: | G protein-coupled receptors (GPCRs) are major drug targets, and their ligands are currently being explored and developed by many pharmaceutical companies and independent researchers. Class A (rhodopsin-like) GPCRs compose a predominant GPCR family; therefore, class A GPCR ligands are in demand. Growth hormone secretagogue receptor (GHS-R) is a class A GPCR that stimulates food intake by binding to its peptide ligand, ghrelin. Therefore, antagonists of GHS-R are expected to exert antiobesity function. In this article, we describe the use of cDNA display to screen for successfully and identify an antagonistic peptide of GHS-R. The antagonistic peptide inhibited the ghrelin-induced increase in intracellular Ca 2+ in vitro (IC 50 = approximately 10 μM) and repressed the contraction of isolated animal stomach in response to ghrelin. Furthermore, peripheral administration of the peptide inhibited the food intake of mice. This work provides new insight into the development of antiobesity drugs and describes a method for the discovery of unique peptide ligands for class A GPCRs. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|