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Spiro(indoline-3,4'-piperidine) growth hormone secretagogues as ghrelin mimetics.

Palucki, B L; Feighner, S D; Pong, S; McKee, K K; Hreniuk, D L; Tan, C; Howard, A D; Van der Ploeg, L H; Patchett, A A; Nargund, R P.

Bioorg Med Chem Lett ; 11(14): 1955-7, 2001 Jul 23.

Article in English | MEDLINE | ID: mdl-11459669

ABSTRACT

A series of small molecules derived from MK-0677, a potent synthetic GHS, mimicking the N-terminal Gly-Ser-O-(n-octanoyl)-L-Ser-Phe segment of ghrelin was synthesized and tested in a binding and in a functional assay measuring intracellular calcium elevation in HEK-293 cells expressing hGHSR1a. Replacement of Phe in this tetrapeptide with a spiro(indoline-3,4'-piperidine) group, Gly-Ser with 2-aminoisobutyric acid, and O-(n-octanoyl)-L-Ser with O-benzyl-D-Ser provided synthetic GHS agonists with similar functional potency as ghrelin.

Subject(s)

Calcium/metabolism , Indoles/metabolism , Peptide Hormones , Peptides/metabolism , Piperidines/metabolism , Receptors, Cell Surface/metabolism , Receptors, G-Protein-Coupled , Spiro Compounds/metabolism , Binding Sites/physiology , Cells, Cultured , Ghrelin , Humans , Indoles/chemistry , Inhibitory Concentration 50 , Luminescence , Molecular Mimicry , Peptides/chemistry , Piperidines/chemical synthesis , Protein Binding/physiology , Receptors, Ghrelin , Spiro Compounds/chemistry

ABSTRACT

Subject(s)

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