A model of reversible inhibitors in the gastric H+/K+-ATPase binding site determined by rotational echo double resonance NMR.

Journal article

Several close analogues of the noncovalent H(+)/K(+)-ATPase inhibitor SCH28080 (2-methyl-3-cyanomethyl-8-(phenylmethoxy)imidazo[1,2-a]pyridine) have been screened for activity and examined in the pharmacological site of action by solid-state NMR spectroscopy. TMPIP, the 1,2,3-trimethyl analogue of SCH28080, and variants of TMPIP containing fluorine in the phenylmethoxy ring exhibited IC(50) values for porcine H(+)/K(+)-ATPase inhibition falling in the sub-10 microm range. Deuterium NMR spectr...

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Authors: Watts, J; Watts, A; Middleton, D

• Publication status: Published
• Journal: Journal of biological chemistry
• Volume: 276
• Issue: 46
• Pages: 43197-43204
• Publication date: 2001-11-01
• DOI: 10.1074/jbc.m104808200
• EISSN: 1083-351X
• ISSN: 0021-9258
• Language: English
• Keywords: Adenosine Triphosphatases; Fluorine; Models, Chemical; Protons; Protein Binding; Models, Molecular; Swine; Animals; Phenylalanine; Binding Sites; Protein Structure, Tertiary; Mutagenesis, Site-Directed; H(+)-K(+)-Exchanging ATPase; Inhibitory Concentration 50; Enzyme Inhibitors; Magnetic Resonance Spectroscopy; Stomach; Imidazoles