A novel DNA polymerase inhibitor and a potent apoptosis inducer: 2-mono-O-acyl-3-O-(alpha-D-sulfoquinovosyl)-glyceride with stearic acid.
ABSTRACT Sulfo-glycolipids in the class of sulfoquinovosyl diacylglycerol (SQDG) including the stereoisomers are potent inhibitors of DNA polymerase alpha and beta. However, since the alpha-configuration of SQDG with two stearic acids (alpha-SQDG-C(18)) can hardly penetrate cells, it has no cytotoxic effect. We tried and succeeded in making a permeable form, sulfoquinovosyl monoacylglycerol with a stearic acid (alpha-SQMG-C(18)) from alpha-SQDG-C(18) by hydrolysis with a pancreatic lipase. alpha-SQMG-C(18) inhibited DNA polymerase activity and was found to be a potent inhibitor of the growth of NUGC-3 cancer cells. alpha-SQMG-C(18) arrested the cell cycle at the G1 phase, and subsequently induced severe apoptosis. The arrest was correlated with an increased expression of p53 and cyclin E, indicating that alpha-SQMG-C(18) induced cell death through a p53-dependent apoptotic pathway.
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ABSTRACT: Methyl 2-benzamido-3,6-di-O-benzoyl-2,4-dideoxy-α-d-glucopyranoside-4-C-sulfonate sodium salt 9 and its galacto epimer 10 were prepared by oxidation with hydrogen peroxide in acetic acid of methyl 4-S-acetyl-2-benzamido-3,6-di-O-benzoyl-2-deoxy-4-thio-α-d-glucopyranoside 7 and its galacto epimer 8, respectively. The 4-thioglucoside 7 was prepared from methyl 2-benzamido-3,6-di-O-benzoyl-2-deoxy-α-d-glucopyranoside by double inversion through triflation, inversion at C-4 with NaNO2, triflation of the resulting methyl 2-benzamido-3,6-di-O-benzoyl-2-deoxy-α-d-galactopyranoside, followed by displacement with potassium thioacetate. Deacylation of 9 with refluxing aqueous sodium hydroxide followed by deionisation yielded methyl 2-amino-2,4-dideoxy-α-d-glucopyranoside-4-C-sulfonic acid 11. Deacylation of the galactopyranoside 10 under the same conditions also gave 11, due to base catalysed isomerisation of galacto to the more stable gluco configuration. The structure of 11, crystallized as the monohydrate, was confirmed by X-ray crystallographic analysis. The asymmetric unit contains two sugar molecules in two unique but similar conformations and two water molecules. The sulfo and the amino groups form a zwitterion, with each ammonium group hydrogen bonded to the sulfonate groups of two other molecules related by symmetry.Tetrahedron Asymmetry 11/2003; 14(23):3761-3768. DOI:10.1016/j.tetasy.2003.10.004
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ABSTRACT: Synthesis of β-glyco-1,2-diacylglycerols is achieved by a versatile and simple procedure based on trichloro-acetimidate methodology and use of peracetate sugar substrates. The chemical strategy was tested through stereoselective preparation of β-galacto- and β-gluco-lipid derivatives capable to trigger immune system response. The synthetic approach is designed to obtain enantiomerically pure regio- and stereo-isomers including derivatives containing poly-unsaturated fatty acids.Tetrahedron Letters 02/2012; 53(7):879–881. DOI:10.1016/j.tetlet.2011.12.030
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ABSTRACT: Recent advances in the area of glycobiology have been paralleled by progress in our understanding of the physical properties of glycoglycerolipids (GGLs). These advances have been accelerated by interest in the new found roles of these simple glycolipids in nature, by advances in synthetic procedures, and by an interest in the technological application of a group of amphiphiles with unique physical and chemical properties. Here, we consider the phase properties of some GGL/water systems containing either a single hexopyranoside or pentopyranoside headgroup. Recent calorimetric and X-ray diffraction measurements of some GGL diastereomers suggest that both headgroup and interfacial hydration play a major role in determining both lyotropism and mesomorphic phase properties as the chemical structure of the lipid headgroup, interface and hydrocarbon chains are systematically altered. For GGLs of a given chain length, interactions between the headgroup/interface and water determine whether or not a highly ordered, lamellar crystalline phase is formed, the number of such phases and their rate of formation and, in some cases, the nature of the molecular packing of those phases. In the liquid crystalline phases, the hydrocarbon chains determine the area per molecule in the lamellar liquid crystalline phase, but it is the cross-sectional area of the hydrated headgroup and the penetration of water into the interface which determines the nature of the non-lamellar phases, probably through small changes in interfacial geometry as the lateral stresses in the headgroup region increase.Current Opinion in Colloid & Interface Science 04/2004; DOI:10.1016/j.cocis.2004.01.009