- TRACERS FOR MONITORING THE ACTIVITY OF SODIUM/GLUCOSE COTRANSPORTERS IN HEALTH AND DISEASE
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Radiolabeled tracers for sodium/glucose cotransporters (SGLTs), their synthesis, and their use are provided. The tracers are methyl or ethyl pyranosides having an equatorial hydroxyl group at carbon-2 and a C1 preferred conformation, radio-labeled with 18F, 123I, or 124I, or free hexoses radiolabeled with 18F, 123I, or 124I. Also provided are in vivo and in vitro techniques for using these and other tracers as analytical and diagnostic tools to study glucose transport, in health and disease, and to evaluate therapeutic interventions.
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- Synthesis of UDP-4-deoxy-4-fluoroglucose and UDP-4-deoxy-4-fluorogalactose and their interactions with enzymes of nucleotide sugar metabolism
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Fluorinated carbohydrates can be used as probes of enzymatic active sites. We report the synthesis of 4-deoxy-4-fluoro-α-D-galactose-1-phosphate and the substrate analogues of UDP-galactose, UDP4-deoxy-4-fluoro-α-D-galactose (UDP-FGal), and of UDP-glucose, UDP-4-deoxy-4-fluoro-α-D-glucose (UDP-FGlc), which may be useful in analyzing the binding properties of enzymes that utilize nucleotide sugars as substrates. As a first step in this study, we determine the kinetic and inhibition parameters for UDP-FGal and UDP-FGlc interacting with UDP-glucose dehydrogenase and UDP-galactose 4-epimerase. UDP-FGlc is a substrate for bovine liver UDP-glucose dehydrogenase: K(m) = 30.2 ± 4.5 μM slightly higher than the value 9.6 ± 0.7 μM for UDP-glucose, and V(m)(UDP-FGlc) = 0.46V(mUDP-Glc). UDP-FGal is not a substrate for UDP-glucose dehydrogenase but is a competitive inhibitor with respect to UDP-glucose (K(i) = 19.9 ± 6.6 μM). These analogs also bind to UDP-galactose 4-epimerase from E. coli with dissociation constants K(d) of 1.4 and 1.1 mM for UDP-FGlc and UDP-FGal, respectively.
- Chapeau,Frey
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p. 6994 - 6998
(2007/10/02)
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- Synthesis and n.m.r. spectra of methyl 2-deoxy-2-fluoro- and 3-deoxy-3-fluoro-alpha- and beta-D-glucopyranosides.
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Methyl 3-deoxy-3-fluoro-alpha- and beta-D-glucopyranosides and alpha- and beta-D-glucofuranosides were prepared by methanolysis of 3-deoxy-3-fluoro-1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose. Crystalline 3,4,6-tri-O-acetyl-2-deoxy-2-fluoro-alpha-D-
- Kovac,Yeh,Glaudemans
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- THE SYNTHESIS AND HYDROLYSIS OF A SERIES OF DEOXYFLUORO-D-GLUCOPYRANOSYL PHOSPHATES
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The synthesis of all four deoxyfluoro-α-D-glucopyranosyl phosphates is described.Rate conctants for their acid-catalyzed hydrolysis were determined, and fluorine substitution was shown to have a significant effect in lowering the rate, particularly when t
- Withers, Stephen G.,MacLennan, David J.,Street, Ian P.
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p. 127 - 144
(2007/10/02)
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- Fluorinated Carbohydrates. 2. Selective Fluorination of Gluco- and Mannopyranosides. Use of 2-D NMR for Structural Assignments
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Methyl and phenyl α-glucosides, or suitably protected derivatives, may be selectively fluorinated with (diethylamino)sulfur trifluoride (DAST) at the 4- or 6-position to afford the corresponding fluorinated galacto- or glucopyranoside.In contrast to the α-glucosides, the β-glucosides underwent ring fluorination at C-3 to give the 3-deoxy-3-fluoro-β-allo derivatives.High yields of primary fluorinated (C-6) products were obtained from both α- and β glucosides by use of appropriate reaction times.Use of 6-O-trityl derivatives of methyl α- and β-glucosides gave methyl 4-deoxy-4-fluoro-α-galactopyranoside (22) and methyl 3-deoxy-3-fluoro-β-allopyranoside (19), respectively.Use of 2-D NMR (COSY) for structural assignements is also described.Fluorinated p-nitrophenyl α- and β-gluco- and -galactopyranosides (such as 15) have also been prepared by the above DAST reactions. 6-O-Pivaloate esters of methyl α-gluco-and α- and β-galactopyranoside have been prepared as an acid and DAST-stable 6-O protecting group.Proof of an intramolecular fluoride-ion delivery mechanism for the SN2 displacement reaction at C-4 in methyl α-D-mannopyranoside is described.Methyl 4-amino-4,6-dideoxy-6-fluoro-α-D-glucopyranoside, methyl 6-amino-3,6-dideoxy-3-fluoro-β-D-allopyranoside, and methyl 6-amino-4,6-dideoxy-4-fluoro-α-D-talopyranoside were also prepared via the above methodology.
- Card, Peter J.,Reddy, Gade S.
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p. 4734 - 4743
(2007/10/02)
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