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