The Experts below are selected from a list of 12 Experts worldwide ranked by ideXlab platform
H. Van Den Bosch - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate Diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions
1991Co-Authors: G. M. T. Van Wijk, Karl Y. Hostetler, Michael Schlame, H. Van Den BoschAbstract:We recently synthesized phospholipid analogs with antiviral nucleosides in the polar headgroup and demonstrated their antiretroviral activity in vitro in human immunodeficiency virus-infected cells (Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. (1990) J. Biol. Chem. 265, 6112–6117). Dideoxynucleoside analogs of Cytidine Diphosphate Diglyceride (CDP-DG) represent one class of such phospholipid prodrugs from which the antiviral active principle may be released through established pathways of cellular phospholipid metabolism. We now demonstrate that the liponucleotides of dideoxyCytidine, 3′-deoxythymidine and 3′-azido-3′-deoxythymidine (AZT, Zidovudine) can substitute to varying extents for CDP-DG in the biosynthesis of phosphatidylinositol, phosphatidylglycerol or diphosphatidylglycerol by rat liver subcellular fractions. In all three biosynthetic pathways dideoxyCytidine Diphosphate Diglyceride was the most active donor of the phosphatidyl unit. The nearly stoichiometric formation of dideoxyCytidine-5′-monophosphate during phosphatidylinositol biosynthesis supports the rationale that the antiretroviral liponucleotides may provide cells with a depot form from which the antiviral drug can be released in 5′-monophosphorylated form, thus bypassing the initial phosphorylation of free dideoxynucleosides.
G. M. T. Van Wijk - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate Diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions
1991Co-Authors: G. M. T. Van Wijk, Karl Y. Hostetler, Michael Schlame, H. Van Den BoschAbstract:We recently synthesized phospholipid analogs with antiviral nucleosides in the polar headgroup and demonstrated their antiretroviral activity in vitro in human immunodeficiency virus-infected cells (Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. (1990) J. Biol. Chem. 265, 6112–6117). Dideoxynucleoside analogs of Cytidine Diphosphate Diglyceride (CDP-DG) represent one class of such phospholipid prodrugs from which the antiviral active principle may be released through established pathways of cellular phospholipid metabolism. We now demonstrate that the liponucleotides of dideoxyCytidine, 3′-deoxythymidine and 3′-azido-3′-deoxythymidine (AZT, Zidovudine) can substitute to varying extents for CDP-DG in the biosynthesis of phosphatidylinositol, phosphatidylglycerol or diphosphatidylglycerol by rat liver subcellular fractions. In all three biosynthetic pathways dideoxyCytidine Diphosphate Diglyceride was the most active donor of the phosphatidyl unit. The nearly stoichiometric formation of dideoxyCytidine-5′-monophosphate during phosphatidylinositol biosynthesis supports the rationale that the antiretroviral liponucleotides may provide cells with a depot form from which the antiviral drug can be released in 5′-monophosphorylated form, thus bypassing the initial phosphorylation of free dideoxynucleosides.
Karl Y. Hostetler - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate Diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions
1991Co-Authors: G. M. T. Van Wijk, Karl Y. Hostetler, Michael Schlame, H. Van Den BoschAbstract:We recently synthesized phospholipid analogs with antiviral nucleosides in the polar headgroup and demonstrated their antiretroviral activity in vitro in human immunodeficiency virus-infected cells (Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. (1990) J. Biol. Chem. 265, 6112–6117). Dideoxynucleoside analogs of Cytidine Diphosphate Diglyceride (CDP-DG) represent one class of such phospholipid prodrugs from which the antiviral active principle may be released through established pathways of cellular phospholipid metabolism. We now demonstrate that the liponucleotides of dideoxyCytidine, 3′-deoxythymidine and 3′-azido-3′-deoxythymidine (AZT, Zidovudine) can substitute to varying extents for CDP-DG in the biosynthesis of phosphatidylinositol, phosphatidylglycerol or diphosphatidylglycerol by rat liver subcellular fractions. In all three biosynthetic pathways dideoxyCytidine Diphosphate Diglyceride was the most active donor of the phosphatidyl unit. The nearly stoichiometric formation of dideoxyCytidine-5′-monophosphate during phosphatidylinositol biosynthesis supports the rationale that the antiretroviral liponucleotides may provide cells with a depot form from which the antiviral drug can be released in 5′-monophosphorylated form, thus bypassing the initial phosphorylation of free dideoxynucleosides.
Michael Schlame - One of the best experts on this subject based on the ideXlab platform.
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Cytidine Diphosphate Diglyceride analogs of antiretroviral dideoxynucleosides: evidence for release of dideoxynucleoside-monophosphates by phospholipid biosynthetic enzymes in rat liver subcellular fractions
1991Co-Authors: G. M. T. Van Wijk, Karl Y. Hostetler, Michael Schlame, H. Van Den BoschAbstract:We recently synthesized phospholipid analogs with antiviral nucleosides in the polar headgroup and demonstrated their antiretroviral activity in vitro in human immunodeficiency virus-infected cells (Hostetler, K.Y., Stuhmiller, L.M., Lenting, H.B.M., van den Bosch, H. and Richman, D.D. (1990) J. Biol. Chem. 265, 6112–6117). Dideoxynucleoside analogs of Cytidine Diphosphate Diglyceride (CDP-DG) represent one class of such phospholipid prodrugs from which the antiviral active principle may be released through established pathways of cellular phospholipid metabolism. We now demonstrate that the liponucleotides of dideoxyCytidine, 3′-deoxythymidine and 3′-azido-3′-deoxythymidine (AZT, Zidovudine) can substitute to varying extents for CDP-DG in the biosynthesis of phosphatidylinositol, phosphatidylglycerol or diphosphatidylglycerol by rat liver subcellular fractions. In all three biosynthetic pathways dideoxyCytidine Diphosphate Diglyceride was the most active donor of the phosphatidyl unit. The nearly stoichiometric formation of dideoxyCytidine-5′-monophosphate during phosphatidylinositol biosynthesis supports the rationale that the antiretroviral liponucleotides may provide cells with a depot form from which the antiviral drug can be released in 5′-monophosphorylated form, thus bypassing the initial phosphorylation of free dideoxynucleosides.
R. Bittman - One of the best experts on this subject based on the ideXlab platform.
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hydrolysis of short acyl chain inositol lipids by phospholipase c delta 1
1993Co-Authors: Mario J. Rebecchi, Robert T. Eberhardt, T. Delaney, S. Ali, R. BittmanAbstract:We investigated the relationship between substrate aggregation and activation of phosphoinositide-specific phospholipase C-delta 1 (PLC-delta 1), isolated from bovine brain cytosol. The inositol lipids 1,2-dibutyryl-sn-glycero-3-phosphoinositol (di-C4-PI), 1,2-dihexanoyl-sn-glycero-3-phosphoinositol (di-C6-PI), and 1,2-dioctanoyl-sn-glycero-3-phosphoinositol (di-C8-PI) were prepared from synthetic Cytidine Diphosphate Diglyceride analogs in a reaction with myo-inositol catalyzed by yeast phosphatidylinositol synthase. All three lipids served as substrates for PLC-delta 1 at concentrations significantly below their critical micelle concentration (cmc). Under these conditions, steps that might limit the reaction rate, such as membrane adsorption or penetration into the phospholipid surface, were eliminated. Below the cmc, the concentration of lipid substrate required to produce hydrolysis followed the order: di-C8-PI < di-C6-PI << di-C4-PI. Calcium was essential for hydrolysis of the short chain substrates at all lipid concentrations tested. The dependence of the reaction on calcium suggests that this ion activates PLC-delta 1 at a step other than adsorption to or penetration of the membrane surface. As the concentration of di-C8-PI was raised above the cmc, the reaction velocity increased 2-3-fold. These results are consistent with the idea that micellar or bilayer aggregates of phosphoinositol are not required for PLC-catalyzed hydrolysis, although the reaction rate is enhanced by micelle formation.
