Abstract
The interaction between the 1-47 N-terminus of the CCK(1)-R and the anthranilic acid based antagonists has been investigated by fluorescence spectroscopy. These antagonists interact with W39 of the N-terminal domain of the CCK(1)-R like that of the endogenous ligand CCK-8. This specific interaction was not found in other nonpeptide ligands of the CCK(1)-R. Conformational studies, using NMR and energy minimization procedures, have allowed formulation of a new hypothesis on the CCK(1)-R binding mode of the anthranilic antagonists.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Binding, Competitive / drug effects
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Biological Assay
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Humans
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Indoles / chemistry
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Indoles / pharmacology
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Ligands
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Magnetic Resonance Spectroscopy
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Models, Molecular
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Molecular Structure
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Pancreas / drug effects
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Pancreas / metabolism
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Proglumide / analogs & derivatives
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Proglumide / chemistry
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Proglumide / pharmacology
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Protein Conformation
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Rats
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Receptor, Cholecystokinin A / antagonists & inhibitors*
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Receptor, Cholecystokinin A / chemistry
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Sincalide / chemistry
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Sincalide / pharmacology*
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Spectrometry, Fluorescence
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Structure-Activity Relationship
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ortho-Aminobenzoates / chemistry*
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ortho-Aminobenzoates / pharmacology*
Substances
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Indoles
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Ligands
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Receptor, Cholecystokinin A
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VL-0395
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ortho-Aminobenzoates
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anthranilic acid
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loxiglumide
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Proglumide
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Sincalide