Inhibition of jack bean urease by thiols.

Kot, Michalina; Zaborska, Wiesława; Juszkiewicz, A.

doi:10.1016/s0040-6031(00)00451-2

Cited by 9 publications

(4 citation statements)

References 23 publications

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“…The most potent inactivators are phosphordiamides, which are classical transition state analogues (Faraci et al 1995 ; Dominguez et al 2008 ). Hydroxamates (Kobashi et al 1962 , 1971 , 1975 ; Odake et al 1992 , 1994 ), imidazoles (Nagata et al 1993 ; Kuehler et al 1995 ), benzoquinones (Zaborska et al 2002 ; Ashiralieva and Kleiner 2003 ), thiols (Ambrose et al 1950 ; Kot et al 2000 ), thioureas and selenoureas constitute other classes (Sivapriya et al 2007 ). However, the most effective structures (particularly phosphordiamidates) lack stability in aqueous environments.…”

Section: Introductionmentioning

confidence: 99%

N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases

et al. 2011

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Small unextended molecules based on the diamidophosphate structure with a covalent carbon-to-phosphorus bond to improve hydrolytic stability were developed as a novel group of inhibitors to control microbial urea decomposition. Applying a structure-based inhibitor design approach using available crystal structures of bacterial urease, N-substituted derivatives of aminomethylphosphonic and P-methyl-aminomethylphosphinic acids were designed and synthesized. In inhibition studies using urease from Bacillus pasteurii and Canavalia ensiformis, the N,N-dimethyl derivatives of both lead structures were most effective with dissociation constants in the low micromolar range (Ki = 13 ± 0.8 and 0.62 ± 0.09 μM, respectively). Whole-cell studies on a ureolytic strain of Proteus mirabilis showed the high efficiency of N,N-dimethyl and N-methyl derivatives of aminomethane-P-methylphosphinic acids for urease inhibition in pathogenic bacteria. The high hydrolytic stability of selected inhibitors was confirmed over a period of 30 days using NMR technique.

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Section: Introductionmentioning

confidence: 99%

N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases

et al. 2011

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“…In all processes mentioned above, the enzyme is exposed to inhibition by different substances. The major classes of urease inhibitors have been investigated, namely hydroxamic acids,6 phosphoroamide compounds,7 boric and boronic acids,7,8 and heavy metal ions 9. The inhibition of urease provides a sensitive screening test for copper and mercury10,11 and a less sensitive test for nickel, cadmium, lead and zinc 12…”

Section: Introductionmentioning

confidence: 99%

Kinetic Parameters of Urease Immobilized on Modified Acrylonitrile Copolymer Membranes in the Presence and Absence of Cu(II) Ions

Godjevargova

Gabrovska

2005

Macromolecular Bioscience

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Poly(acrylonitrile-methylmethacrylate-sodium vinylsulfonate) membranes were subjected to seven different chemical modifications and the amount of the newly formed groups was measured for each membrane. Urease was then covalently immobilized onto the modified membranes and the amount of bound protein was determined. The kinetic parameters V(max) and K(m) of the immobilized urease were studied under static and dynamic conditions. Results showed that the rate of the enzyme reaction was higher for the membranes modified with NH(2)OH . H(2)SO(4), NH(2)NH(2) . H(2)SO(4), NaOH + EDA and NaOH + GA + EDA. It was confirmed that the reaction rate, measured under dynamic conditions, was higher than that one determined under static conditions. The influence of Cu(II) ions, as inhibitors, on the enzyme reaction kinetics (V(i) and K(i)) was also investigated. It turned out that the most sensitive membranes towards Cu(II) were those modified with NH(2)NH(2) . H(2)SO(4), NaOH + EDA and H(2)O(2). The results initiated further investigations on the influence of other heavy metal ions (Cd(II), Zn(II), Ni(II) and Pb(II)) over urease bound to a NH(2)OH . H(2)SO(4)-modified membrane. It was found that the inhibition effect of the heavy metal ions over immobilized urease decreases in the order: Cu(II) > Cd(II) > Zn(II) > Ni(II) > Pb(II). [Diagram: see text]

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“…Since there are structural similarities with urea, there is potential to allow for a binding mode that resembles that of the native enzyme–substrate complex and the consideration of the innate substrate specificity of the urease enzyme. Furthermore, the proposed 2-MA inhibitor contains a thiol moiety, which is known to display active inhibition of the urease enzyme, as described elsewhere 23 , 24 . Urease inhibitors have been extensively examined by previous researchers as described by 25 , 26 .…”

Section: Introductionmentioning

confidence: 99%

A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

Milo

Heylen

Glancy

et al. 2021

Sci Rep

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Infection and blockage of indwelling urinary catheters is significant owing to its high incidence rate and severe medical consequences. Bacterial enzymes are employed as targets for small molecular intervention in human bacterial infections. Urease is a metalloenzyme known to play a crucial role in the pathogenesis and virulence of catheter-associated Proteus mirabilis infection. Targeting urease as a therapeutic candidate facilitates the disarming of bacterial virulence without affecting bacterial fitness, thereby limiting the selective pressure placed on the invading population and lowering the rate at which it will acquire resistance. We describe the design, synthesis, and in vitro evaluation of the small molecular enzyme inhibitor 2-mercaptoacetamide (2-MA), which can prevent encrustation and blockage of urinary catheters in a physiologically representative in vitro model of the catheterized urinary tract. 2-MA is a structural analogue of urea, showing promising competitive activity against urease. In silico docking experiments demonstrated 2-MA’s competitive inhibition, whilst further quantum level modelling suggests two possible binding mechanisms.

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Inhibition of jack bean urease by thiols.

Cited by 9 publications

References 23 publications

N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases

N-substituted aminomethanephosphonic and aminomethane-P-methylphosphinic acids as inhibitors of ureases

Kinetic Parameters of Urease Immobilized on Modified Acrylonitrile Copolymer Membranes in the Presence and Absence of Cu(II) Ions

A small-molecular inhibitor against Proteus mirabilis urease to treat catheter-associated urinary tract infections

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