Inhibitors of angiotensin-converting enzyme containing a tetrahedral arsenic atom.
A series of tetrahedral oxo acids of Group VA and VIA elements and of silicon and boron were examined as inhibitors of angiotensin-converting enzyme. Arsenate is a competitive inhibitor with a Ki of 27 +/- 1 mM, at least 10-fold more potent than phosphate. Dimethylarsinate is a competitive inhibitor with a Ki of 70 +/- 9 mM, 2-fold more potent than dimethylphosphinate. Oxo acids of boron, silicon, antimony, sulphur and selenium are not inhibitors. On the basis of these results and the strong inhibition of this zinc metallopeptidase by substrate analogues containing a tetrahedral phosphorus atom, two substrate analogues containing a tetrahedral arsenic atom were prepared. 2-Arsonoacetyl-L-proline is a competitive inhibitor with a Ki of 18 +/- 7 mM, more than 2000-fold weaker than that of its phosphorus analogue 2-phosphonoacetyl-L-proline. 4-Arsono-2-benzylbutanoic acid is a mixed inhibitor with a Ki of 0.5 +/- 0.2 mM, indistinguishable in potency from its phosphorus analogue 2-benzyl-4-phosphonobutanoic acid.
Galardy
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Kortylewicz
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D000806:Angiotensin-Converting Enzyme Inhibitors; D001149:Arsenates / Q000494:pharmacology*; D001151:Arsenic / Q000494:pharmacology*; D001665:Binding Sites; D007700:Kinetics; D008956:Models, Chemical; D008968:Molecular Conformation; D010756:Phosphoric Acids / Q000494:pharmacology*
D000806:Angiotensin-Converting Enzyme Inhibitors; D001149:Arsenates; D010756:Phosphoric Acids; D001151:Arsenic; C025657:arsenic acid