Model Reactions of Phosphorus-containing Enzyme Inactivators. IV.<sup>1a</sup> The Catalytic Activity of Certain Metal Salts and Chelates in the Hydrolysis of Diisopropyl Fluorophosphate<sup>1b</sup>

Wagner‐Jauregg, Theodor; Hackley, Brennie E.; Lies, T. A.; Owens, Omer O.; Proper, Reuben

doi:10.1021/ja01609a037

Cited by 104 publications

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“…Cupric ion and imidazole catalyze the hydrolysis of DFP with the release of hydrofluoric acid (17); in these experiments the decrease in pH confirmed that the reaction was proceeding. In four experiments, the clotting time of the untreated thrombin control and the purified cancer procoagulant sample was 112±4 and 130±8 s, respectively, after normalizing the results to a 200-s blank time.…”

Section: Introductionmentioning

confidence: 53%

A factor X-activating cysteine protease from malignant tissue.

Gordon¹,

Cross²

1981

J. Clin. Invest.

224

109

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A B S T R A C T A proteolytic procoagulant has been identified in extracts of human and animal tumors and in cultured malignant cells. It directly activated Factor X but its similarity to other Factor X-activating serine proteases was not clear. This study describes work done to determine whether this enzyme, cancer procoagulant, is a serine or cysteine protease. Purified cancer procoagulant from rabbit V2 carcinoma was bound to a p-chloromercurialbenzoate-agarose affinity column and was eluted with dithiothreitol. The initiation of recalcified, citrated plasma coagulation activity by cancer procoagulant was inhibited by 5 mM diisopropylfluorophosphate, 1 mM phenylmethylsulfonylfluoride, 0.1 mM HgCl2, and 1 mM iodoacetamide. Activity was restored in the diisopropylfluorophosphate-, phenylmethylsulfonylfluoride-, and HgCl2-inhibited samples by 5 mM dithiothreitol; iodoacetamide inhibition was irreversible. Russell's viper venom, a control Factor Xactivating serine protease, was not inhibited by either 0.1 mM HgCl2 or 1 mM iodoacetamide. The direct activation ofFactor X by cancer procoagulant in a two-stage assay was inhibited by diisopropylfluorophosphate and iodoacetamide. Diisopropylfluorophosphate inhibits serine proteases, and an undefined impurity in most commercial preparations inhibits cysteine proteases. Hydrolysis of diisopropylfluorophosphate with CuS04 and imidazole virtually eliminated inhibition of thrombin, but cancer procoagulant inhibition remained complete, suggesting that cancer procoagulant was inhibited by the undefined impurity. These results suggest that cancer procoagulant is a cysteine endopeptidase, which distinguishes it from other coagulation factors including tissue factor. This and other data suggest that neoplastic cells produce this unique cysteine protease which may initiate blood coagulation.

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Section: Introductionmentioning

confidence: 53%

A factor X-activating cysteine protease from malignant tissue.

Gordon¹,

Cross²

1981

J. Clin. Invest.

224

109

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“…Some of these interact strongly with organophosphonates such as the nerve-agent simulant diisopropyl methylphosphonate (DIMP) and, presumably, the Type G nerve agents to which it is related. We chose to examine the Au/MUACu 2+ interface in detail because Cu 2+ is a hydrolysis catalyst for certain nerve agents, 17 and we reasoned that good catalytic materials would also perform well as sensor interfaces since both involve selective and reversible interactions with analytes. The metal-ion/acid bilayers are very easy to prepare.…”

Section: Simple Bilayersmentioning

confidence: 99%

New Organic Materials Suitable for Use in Chemical Sensor Arrays

1998

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“…Of interest in this connection is also that the hydrolysis of diisopropyl fluorophosphate is catalyzed by several Cu2+ complexes, among which the Cu2+-bipyridyl I : 1 complex is especially effective. Furthermore, in addition to the Cu2+ complex with 2,2'-bipyridyl, the complexes of L-histidine, 1,lO-phenanthroline, and imidazole are better catalysts than that of glycine [41].…”

Section: Discussionmentioning

confidence: 99%

Ternary Complexes in Solution

Huber

Griesser

Prijs

et al. 1969

European Journal of Biochemistry

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The stability constants of the ternary Cuz+ complexes, ethylenediamine-Cu2+-pyrocatechol and histamine-Cua+-pyrocatechol dianion, were determined. Both complexes are more stable than one would expect on pure statistical reasons. The imidazole-containing ternary Cuz+ complex is, however, especially stable. For the equilibrium, Cu(histamine), + Cu(pyrocatechol), ~2[(histamine)Cu(pyrocatechol)], the constant is log X = 4.86 (I = 0.1; T = 25"), while the statistical value is 0.6. These results were compared with those taken (or calculated) from the literature; it is concluded that the n-system of the ligands is important for such a great increase in stability. Furthermore, the Cuz+-histamine I : 1 complex selectively binds to 0-ligands rather than to N-ligands. Thus, the first coordinated ligand has an influence on the kind of the second to be coordinated, i. e. the Cua+-histamine 1 : 1 complex shows discriminating qualities. The significance of these results is discussed with regard to Cu-proteins, since it is suggested for several enzymes that the imidazole group of histidine is involved with the binding of metal ions.I n general, ternary complexes, i.e. mixed ligand metal ion complexes, can be considered as models [2] for enzyme-metal ion-substrate complexes [3,4]. Furthermore, such ternary complexes probably occur in biological fluids that contain several ligands as well as different metal ions. Investigations of the stability of ternary complexes may, therefore, help toward understanding the driving forces which lead to the formation of such complexes in biological systems. The importance of mixed complexes in nature is evident, since a great deal of biochemical reactions occur in such complexes, i.e. within the coordination sphere of metal ions [3,4].I n addition, the investigation of ternary Cu2+ complexes, containing an imidazole group as binding site, is of special interest, since it is suggested for several proteins which interact with Cua+ and for natural Cu-proteins that the imidazole group of histidine binds to copper. Thus, the Cuz+ complexes of several histidine-containing peptides

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Model Reactions of Phosphorus-containing Enzyme Inactivators. IV.^1a The Catalytic Activity of Certain Metal Salts and Chelates in the Hydrolysis of Diisopropyl Fluorophosphate^1b

Cited by 104 publications

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A factor X-activating cysteine protease from malignant tissue.

A factor X-activating cysteine protease from malignant tissue.

New Organic Materials Suitable for Use in Chemical Sensor Arrays

Ternary Complexes in Solution

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Model Reactions of Phosphorus-containing Enzyme Inactivators. IV.1a The Catalytic Activity of Certain Metal Salts and Chelates in the Hydrolysis of Diisopropyl Fluorophosphate1b

Cited by 104 publications

References 0 publications

A factor X-activating cysteine protease from malignant tissue.

A factor X-activating cysteine protease from malignant tissue.

New Organic Materials Suitable for Use in Chemical Sensor Arrays

Ternary Complexes in Solution

Contact Info

Product

Resources

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Model Reactions of Phosphorus-containing Enzyme Inactivators. IV.^1a The Catalytic Activity of Certain Metal Salts and Chelates in the Hydrolysis of Diisopropyl Fluorophosphate^1b