Synthesis of ?-ketophosphonic acids

Khomutov, R. M.; Osipova, T. I.; Zhukov, Yu. N.

doi:10.1007/bf00923378

Cited by 4 publications

(2 citation statements)

References 5 publications

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“…8A) followed in 1967 [108]. In the late 1970s, Kluger & Pike [109] and Khomutov et al [110] introduced the free phosphonic acid (I, Fig. 8A) and its monoesters (IIIa,b, Fig.…”

Section: Phosphonate Analogs Of 2-oxo Acids As Tools To Specifically mentioning

confidence: 99%

Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models

Bunik

Tylicki

Lukashev

2013

FEBS J

102

128

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Bringing a knowledge of enzymology into research in vivo and in situ is of great importance in understanding systems biology and metabolic regulation. The central metabolic significance of thiamin (vitamin B 1 ) and its diphosphorylated derivative (thiamin diphosphate; ThDP), and the fundamental differences in the ThDP-dependent enzymes of metabolic networks in mammals versus plants, fungi and bacteria, or in health versus disease, suggest that these enzymes are promising targets for biotechnological and medical applications. Here, the in vivo action of known regulators of ThDP-dependent enzymes, such as synthetic structural analogs of the enzyme substrates and thiamin, is analyzed in light of the enzymological data accumulated during half a century of research. Mimicking the enzyme-specific catalytic intermediates, the phosphonate analogs of 2-oxo acids selectively inhibit particular ThDP-dependent enzymes. Because of their selectivity, use of these compounds in cellular and animal models of ThDP-dependent enzyme malfunctions improves the validity of the model and its predictive power when compared with the nonselective and enzymatically less characterized oxythiamin and pyrithiamin. In vitro studies of the interaction of thiamin analogs and their biological derivatives with potential in vivo targets are necessary to identify and attenuate the analog selectivity. For both the substrate and thiamin synthetic analogs, in vitro reactivities with potential targets are highly relevant in vivo. However, effective concentrations in vivo are often higher than in vitro studies would suggest. The significance of specific inihibition of the ThDP-dependent enzymes for the development of herbicides, antibiotics, anticancer and neuroprotective strategies is discussed.

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“…8A) followed in 1967 [108]. In the late 1970s, Kluger & Pike [109] and Khomutov et al [110] introduced the free phosphonic acid (I, Fig. 8A) and its monoesters (IIIa,b, Fig.…”

Section: Phosphonate Analogs Of 2-oxo Acids As Tools To Specifically mentioning

confidence: 99%

Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models

Bunik

Tylicki

Lukashev

2013

FEBS J

102

128

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“…Analysis of the phosphonate interaction with the enzymes pointed to the formation of the tight complexes, some of which have subsequently been crystallized [61,62], suggesting that these were strongly dependent on specific catalytic events. Bunik et al [63] were the first to demonstrate potent inhibition of the animal OGDH component of OGDHC by the phosphonate analogue of OG, SP (succinyl phosphonate) ( Figure 4), synthesized as described by Khomutov et al [64]. Further studies indicated that the inhibition of the OGDH by this analogue, as well as some of its esters, was also extremely efficient within the native structure of the integral OGDHC from bacterial, plant and animal sources [63,[65][66][67][68].…”

Section: Developing Inhibitors Of Ogdhc For In Vivo Studies Specific mentioning

confidence: 99%

Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation

Bunik

Fernie

2009

Biochemical Journal

117

120

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Mechanism-based inhibitors and both forward and reverse genetics have proved to be essential tools in revealing roles for specific enzymatic processes in cellular function. Here, we review experimental studies aimed at assessing the impact of OG (2-oxoglutarate) oxidative decarboxylation on basic cellular activities in a number of biological systems. After summarizing the catalytic and regulatory properties of the OGDHC (OG dehydrogenase complex), we describe the evidence that has been accrued on its cellular role. We demonstrate an essential role of this enzyme in metabolic control in a wide range of organisms. Targeting this enzyme in different cells and tissues, mainly by its specific inhibitors, effects changes in a number of basic functions, such as mitochondrial potential, tissue respiration, ROS (reactive oxygen species) production, nitrogen metabolism, glutamate signalling and survival, supporting the notion that the evolutionary conserved reaction of OG degradation is required for metabolic adaptation. In particular, regulation of OGDHC under stress conditions may be essential to overcome glutamate excitotoxicity in neurons or affect the wound response in plants. Thus, apart from its role in producing energy, the flux through OGDHC significantly affects nitrogen assimilation and amino acid metabolism, whereas the side reactions of OGDHC, such as ROS production and the carboligase reaction, have biological functions in signalling and glyoxylate utilization. Our current view on the role of OGDHC reaction in various processes within complex biological systems allows us a far greater fundamental understanding of metabolic regulation and also opens up new opportunities for us to address both biotechnological and medical challenges.

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The Synthesis of Functionalized Phosphinic and Phosphonic Acids and their Derivatives. Part A: Halo, Hydroxy, Epoxy, Mercapto, Carboxy and Oxo Functionalized Acids

Edmundson¹

2009

Patai's Chemistry of Functional Groups

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Introduction Halo‐Phosphonic and ‐Phosphinic Acids Hydroxy‐Phosphonic and ‐Phosphinic Acids Epoxy‐Phosphonic and ‐Phosphinic Acids Mercapto‐Phosphonic and ‐Phosphinic Acids Phosphonoyl‐ and Phosphinoyl‐Alkanoic Acids and their Derivatives Oxoalkyl‐Phosphonic and ‐Phosphinic Acids

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Synthesis of ?-ketophosphonic acids

Cited by 4 publications

References 5 publications

Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models

Thiamin diphosphate-dependent enzymes: from enzymology to metabolic regulation, drug design and disease models

Metabolic control exerted by the 2-oxoglutarate dehydrogenase reaction: a cross-kingdom comparison of the crossroad between energy production and nitrogen assimilation

The Synthesis of Functionalized Phosphinic and Phosphonic Acids and their Derivatives. Part A: Halo, Hydroxy, Epoxy, Mercapto, Carboxy and Oxo Functionalized Acids

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