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Biochem Biophys Res Commun. 2001 Sep 14;287(1):142-6.

Structure-activity relationship of ghrelin: pharmacological study of ghrelin peptides.

Author information

1
Suntory Institute for Medicinal Research & Development, Kurakake 2716-1, Akaiwa, Chiyoda-machi, Ohra-gun, Gunma 370-0503, Japan.

Abstract

Ghrelin, a novel peptide purified from the stomach, is the endogenous ligand of the growth hormone secretagogue receptor. The Ser(3) residue of ghrelin is modified with a lipid n-octanoic acid, a modification necessary for hormonal activity. To clarify the role of acyl modification and to identify the active core of ghrelin, we examined the activities of partially digested ghrelin and synthetic ghrelin derivatives. The activities confirmed that the N-terminal portion is the active core. Moreover, synthetic ghrelin derivatives demonstrated that octanoic acid is not the only modification of the Ser(3) side chain to sustain the activity of ghrelin; other acyl acid modifications maintained activity. Amino acid replacement of Ser(3) indicated that an L-configuration of the third residue is critical for ghrelin activity. In addition, more stable ether or thioether bonds are capable of replacing the octanoyl ester bond in ghrelin, advantageous for the generation of pharmaceuticals with longer stability.

PMID:
11549267
DOI:
10.1006/bbrc.2001.5553
[Indexed for MEDLINE]

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