Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:6.3.4.6 (urease)
 7,490 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Reaction of the new asymmetric ligand 2-(N-isopropyl-N-((1-methylimidazolyl)methyl)aminomethyl)-6-(N-carboxylmethyl-N-((1-methylimidazolyl)methyl) aminomethyl)-4-methylphenol (ICIMP) with nickel perchlorate and diphenylacetic acid leads to the formation of tetranuclear nickel complexes, whose crystal structures reveal that they consist of dimers of dimers in which each Ni(2) unit has a coordination environment that is similar to the active site of urease. One complex has been shown to coordinate urea and catalyze the hydrolysis of an organophosphate monoester.
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PMID:Hydrolytically active tetranuclear nickel complexes with structural resemblance to the active site of urease. 1235 25

Two new carboxylate-containing polydentate ligands have been synthesized, the symmetric ligand 2,6-bis[N-(N-(carboxylmethyl)-N-((1-methylimidazol)methyl)amine)methyl]-4-methylphenolate (BCIMP) and the corresponding asymmetric ligand 2-(N-isopropyl-N-((1-aminomethyl)-4-methylphenol (ICIMP). The ligands have been used to prepare model complexes for the active site of the dinuclear nickel enzyme urease, viz. [Ni(2)(BCIMP)Ac(2)](-) (6), [Ni(2)(BCIMP)(Ph(2)Ac)(2)](-) (7), [Ni(2)(ICIMP)(Ph(2)Ac)(2)] (14), [Ni(4)(ICIMP)(2)(Ph(2)Ac)(2)][ClO(4)](2) (15), [Ni(4)(ICIMP)(2)(Ph(2)Ac)(2)(DMF)(2)][ClO(4)](2) (16), and [Ni(4)(ICIMP)(2)(Ph(2)Ac)(2)(urea)(H(2)O)][ClO(4)](2) (17), where the latter complex contains urea coordinated in a unidentate fashion through the carbonyl oxygen. The N(2)O-N(2)O(2) donor set of ICIMP provides a good framework for the preparation of urease models, but in some cases tetranuclear nickel complexes are formed due to coordination of the carboxylate moiety of one dinickel-ICIMP unit to one or both of the nickels of a second Ni(2) unit. Reactivity and kinetics studies of 7 and 15 show that these model complexes catalyze hydrolysis of 2-hydroxypropyl p-nitrophenyl phosphate (HPNP) at basic pH. In this assay, complexes based on the asymmetric ligand ICIMP exhibit a significantly faster rate of hydrolysis than the corresponding BCIMP complexes. Magnetic measurements indicate that there are weak antiferromagnetic interactions between the nickel ions in complex 16.
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PMID:Nickel complexes of carboxylate-containing polydentate ligands as models for the active site of urease. 1560 71

A new group of organophosphorus inhibitors of urease, P-methyl phosphinic acids was discovered by using the structure based inhibitor design approach. Several derivatives of the lead compound, aminomethyl(P-methyl)phosphinic acid, were synthesized successfully. Their potency was evaluated in vitro against urease from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a group of competitive, reversible inhibitors of bacterial ureases. Obtained thiophosphinic analogues of the most effective structures exhibited kinetic characteristics of potent, slow binding urease inhibitors, with Ki = 170 nM (against B. pasteurii enzyme) for the most active N-( N'-benzyloxycarbonylglycyl)aminomethyl(P-methyl)phosphinothioic acid.
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PMID:Design, synthesis, and evaluation of novel organophosphorus inhibitors of bacterial ureases. 1871 81

Urease inhibitors can be considered as a tool to control the damaging effect of ureolytic bacteria infections in humans which occur commonly in the developed countries. Computer-aided optimization of the aminomethylphosphinate structures by modifying both their N- and P-termini led to the invention of a novel group of inhibitors of bacterial ureases. Introduction of P-hydroxymethyl group into the molecule resulted in considerable increase of the inhibitory activity against enzymes purified from Bacillus pasteurii and Proteus vulgaris as compared with their P-methyl counterparts described previously. The designed compounds represent a competitive reversible class of urease inhibitors. The most potent, N-methyl-aminomethyl-P-hydroxymethylphosphinic acid, displayed K(i) = 360 nM against P. vulgaris enzyme.
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PMID:Computer-aided optimization of phosphinic inhibitors of bacterial ureases. 2068 1