| 19625579 |
Bennett KA, Langmead CJ, Wise A, Milligan G: Growth hormone secretagogues and growth hormone releasing peptides act as orthosteric super-agonists but not allosteric regulators for activation of the G protein Galpha (o1) by the Ghrelin receptor. Mol Pharmacol. 2009 Oct;76(4):802-11. Epub 2009 Jul 22.
In membranes prepared from cells coexpressing the human ghrelin receptor and the G protein Galpha (o1), N-[1 (R)-1, 2-dihydro-1-ethanesulfonylspiro-3H-indole-3,4'-piperidin)-1'-yl] carbonyl-2 -(phenylmethoxy)-ethyl-2-amino-2-methylpropanamide (MK-677), growth hormone-releasing peptide 6 (GHRP-6), and the 2 (R)-hydroxypropyl derivative of 3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5-yl) (1,1'-biphenyl)-4-yl] methyl)-1H-1-benzazepin-3 (R)-yl)-butanamide (L-692,585) each functioned as direct agonists, and each displayed higher efficacy than ghrelin. |
34(0,1,1,4) |
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| 18923064 |
Holst B, Frimurer TM, Mokrosinski J, Halkjaer T, Cullberg KB, Underwood CR, Schwartz TW: Overlapping binding site for the endogenous agonist, small-molecule agonists, and ago-allosteric modulators on the ghrelin receptor. Mol Pharmacol. 2009 Jan;75(1):44-59. Epub 2008 Oct 15.
A library of robust ghrelin receptor mutants with single substitutions at 22 positions in the main ligand-binding pocket was employed to map binding sites for six different agonists: two peptides (the 28-amino-acid octanoylated endogenous ligand ghrelin and the hexapeptide growth hormone secretagogue GHRP-6) plus four nonpeptide agonists-the original benzolactam L-692,429 [3-amino-3-methyl-N-(2,3,4,5-tetrahydro-2-oxo-1-([2'-(1H-tetrazol-5-yl) (1,1'-biphenyl)-4-yl] methyl)-1H-1-benzazepin-3 (R)-yl)-butanamide], the spiroindoline sulfonamide MK-677 [N-[1 (R)-1, 2-dihydro-1-ethanesulfonylspiro-3H-indole-3,4'-piperidin)-1'-yl] carbonyl-2 -(phenylmethoxy)-ethyl-2-amino-2-methylpropanamide], and two novel oxindole derivatives, SM-130686 [(+)-6-carbamoyl-3-(2-chlorophenyl)-(2-diethylaminoethyl)-4-trifluoromethy loxindole] and SM-157740 [(+/-)-6-carbamoyl-3-(2, 4-dichlorophenyl)-(2-diethylaminoethyl)-4-trifluoromethyloxindole)]. |
33(0,1,1,3) |
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