Overlapping Binding Site for the Endogenous Agonist, Small-Molecule Agonists, and Ago-allosteric Modulators on the Ghrelin Receptor

  title={Overlapping Binding Site for the Endogenous Agonist, Small-Molecule Agonists, and Ago-allosteric Modulators on the Ghrelin Receptor},
  author={Birgitte Holst and Thomas M. Frimurer and Jacek Mokrosiński and Tine Halkjaer and Karina B. Cullberg and Christina Rye Underwood and Thue W. Schwartz},
  journal={Molecular Pharmacology},
  pages={44 - 59}
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… 

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