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J Med Chem. 2000 Nov 16;43(23):4370-6.

Structure-function studies on the new growth hormone-releasing peptide, ghrelin: minimal sequence of ghrelin necessary for activation of growth hormone secretagogue receptor 1a.

Author information

1
Departments of Medicinal Chemistry, Metabolic Disorders, Drug Metabolism, and Membrane Biochemistry and Biophysics, Merck Research Laboratories, R50G-141, P.O. Box 2000, Rahway, New Jersey 07065, USA. maria_bednarek@merck.com

Abstract

The recently discovered growth hormone secretagogue, ghrelin, is a potent agonist at the human growth hormone secretagogue receptor 1a (hGHSR1a). To elucidate structural features of this peptide necessary for efficient binding to and activation of the receptor, several analogues of ghrelin with various aliphatic or aromatic groups in the side chain of residue 3, and several short peptides derived from ghrelin, were prepared and tested in a binding assay and in an assay measuring intracellular calcium elevation in HEK-293 cells expressing hGHSR1a. Bulky hydrophobic groups in the side chain of residue 3 turned out to be essential for maximum agonist activity. Also, short peptides encompassing the first 4 or 5 residues of ghrelin were found to functionally activate hGHSR1a about as efficiently as the full-length ghrelin. Thus the entire sequence of ghrelin is not necessary for activity: the Gly-Ser-Ser(n-octanoyl)-Phe segment appears to constitute the "active core" required for agonist potency at hGHSR1a.

PMID:
11087562
DOI:
10.1021/jm0001727
[Indexed for MEDLINE]

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