Anthranilic acid based CCK1 receptor antagonists and CCK-8 have a common step in their "receptor desmodynamic processes".
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.
De Luca
Stefania
S
Interuniversity Research Center on Bioactive Peptides (CIRPeB), University of Naples Federico II, and Institute of Biostructures and Bioimaging of CNR, Via Mezzocannone, 16 I-80134 Naples, Italy.
Saviano
Michele
M
Lassiani
Lucia
L
Yannakopoulou
Konstantina
K
Stefanidou
Penny
P
Aloj
Luigi
L
Morelli
Giancarlo
G
Varnavas
Antonio
A
D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D001681:Biological Assay; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism; D011377:Proglumide / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D011487:Protein Conformation; D051381:Rats; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors* / Q000737:chemistry; D012844:Sincalide / Q000737:chemistry / Q000494:pharmacology*; D013050:Spectrometry, Fluorescence; D013329:Structure-Activity Relationship; D062367:ortho-Aminobenzoates / Q000737:chemistry* / Q000494:pharmacology*
D007211:Indoles; D008024:Ligands; D043886:Receptor, Cholecystokinin A; C492564:VL-0395; D062367:ortho-Aminobenzoates; C031385:anthranilic acid; C053737:loxiglumide; D011377:Proglumide; D012844:Sincalide