Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in their "receptor desmodynamic processes"

J Med Chem. 2006 Apr 20;49(8):2456-62. doi: 10.1021/jm051050n.

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

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive / drug effects
  • Biological Assay
  • Humans
  • Indoles / chemistry
  • Indoles / pharmacology
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Molecular Structure
  • Pancreas / drug effects
  • Pancreas / metabolism
  • Proglumide / analogs & derivatives
  • Proglumide / chemistry
  • Proglumide / pharmacology
  • Protein Conformation
  • Rats
  • Receptor, Cholecystokinin A / antagonists & inhibitors*
  • Receptor, Cholecystokinin A / chemistry
  • Sincalide / chemistry
  • Sincalide / pharmacology*
  • Spectrometry, Fluorescence
  • Structure-Activity Relationship
  • ortho-Aminobenzoates / chemistry*
  • ortho-Aminobenzoates / pharmacology*

Substances

  • Indoles
  • Ligands
  • Receptor, Cholecystokinin A
  • VL-0395
  • ortho-Aminobenzoates
  • anthranilic acid
  • loxiglumide
  • Proglumide
  • Sincalide