The catalytic C-deuteration of some carbohydrate derivatives

Koch, Hans J.; Stuart, R. S.

doi:10.1016/s0008-6215(00)84123-3

Cited by 48 publications

(15 citation statements)

References 19 publications

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“…for OG): A ) deuterating the alkyl chain at the required deuteration level starting from the corresponding fatty acid and using hydrothermal Pt/C catalysed H/D exchange reactions at 220 °C in the appropriate molar ratio of deuterium and hydrogen atoms in the mixture, reducing the fatty acid molecule to the corresponding alcohol; B ) attaching the deuterated alcohol to the corresponding acetylated bromo‐sugar head group (i.e. 2,3,4,6‐tetra‐O‐acetyl‐α‐D‐glucopyranosyl bromide and 2,3,6,2′,3′,4′,6′‐hepta‐O‐acetyl‐a‐D‐maltosyl bromide) according to standard procedures deacetylation of the sugar head group; C ) deuterating the sugar head to achieve the required deuteration level by using mild conditions of Raney Nickel as a catalyst in D 2 O/H 2 O mixture at 80 °C for 18 h. The latter step allows the incorporation of deuterium atoms on carbons adjacent to free hydroxyl groups (α positions) in the sugar head group with retention of configuration, but it does not affect any H/D back‐exchange at the more inert alkyl chain sites (see Supporting Information 2 for details).…”

Section: Resultsmentioning

confidence: 99%

“…conditions of Raney Nickel as a catalyst in D 2 O/H 2 O mixture at 80°C for 18 h. The latter step allows the incorporation of deuterium atoms on carbons adjacent to free hydroxyl groups (a positions) in the sugar head group with retention of configuration, but it does not affect any H/D back-exchange at the more inert alkyl chain sites [36][37][38] (see Supporting Information 2 for details).…”

Section: Synthesis Of Detergents With Controlled Deuteration Levels Imentioning

confidence: 99%

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Invisible detergents for structure determination of membrane proteins by small‐angle neutron scattering

et al. 2017

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A novel and generally applicable method for determining structures of membrane proteins in solution via small-angle neutron scattering (SANS) is presented. Common detergents for solubilizing membrane proteins were synthesized in isotope-substituted versions for utilizing the intrinsic neutron scattering length difference between hydrogen and deuterium. Individual hydrogen/deuterium levels of the detergent head and tail groups were achieved such that the formed micelles became effectively invisible in heavy water (D O) when investigated by neutrons. This way, only the signal from the membrane protein remained in the SANS data. We demonstrate that the method is not only generally applicable on five very different membrane proteins but also reveals subtle structural details about the sarco/endoplasmatic reticulum Ca ATPase (SERCA). In all, the synthesis of isotope-substituted detergents makes solution structure determination of membrane proteins by SANS and subsequent data analysis available to nonspecialists.

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Section: Resultsmentioning

confidence: 99%

Section: Synthesis Of Detergents With Controlled Deuteration Levels Imentioning

confidence: 99%

Invisible detergents for structure determination of membrane proteins by small‐angle neutron scattering

et al. 2017

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“…Deuterium oxide (D 2 O, 99.92 %) was purchased from Medical Isotopes, Inc. [D 10 ]‐ dl ‐Dithiothreitol ([D 10 ]DTT, 98 %) was purchased from Isotec. Lysozyme and isopropyl‐ d ‐thiogalactopyranoside (IPTG) were purchased from LabScientific, Inc. [D 8 ]Glycerol was prepared according to Koch et al . Acetylated peptide Arg‐His‐Lys‐Lys Ac (>96 %) and fluoroacetylated peptide Arg‐His‐Lys‐Lys Ac ‐AMC (>91 %) were purchased from China Peptides Co. Ltd.…”

Section: Methodsmentioning

confidence: 99%

Studies of the Binding of Modest Modulators of the Human Enzyme, Sirtuin 6, by STD NMR

Bolívar

Welch

2017

ChemBioChem

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Pyrazinamide (PZA), an essential constituent of short-course tuberculosis chemotherapy, binds weakly but selectively to Sirtuin 6 (SIRT6). Despite the structural similarities between nicotinamide (NAM), PZA, and pyrazinoic acid (POA), these inhibitors modulate SIRT6 by different mechanisms and through different binding sites, as suggested by saturation transfer difference (STD) NMR. Available experimental evidence, such as that derived from crystal structures and kinetic experiments, has been of only limited utility in elucidation of the mechanistic details of sirtuin inhibition by NAM or other inhibitors. For instance, crystallographic structural analysis of sirtuin binding sites does not help us understand important differences in binding affinities among sirtuins or capture details of such dynamic process. Hence, STD NMR was utilized throughout this study. Our results not only agreed with the binding kinetics experiments but also gave a qualitative insight into the binding process. The data presented herein suggested some details about the geometry of the binding epitopes of the ligands in solution with the apo- and holoenzyme. Recognition that SIRT6 is affected selectively by PZA, an established clinical agent, suggests that the rational development of more potent and selective NAM surrogates might be possible. These derivatives might be accessible by employing the malleability of this scaffold to assist in the identification by STD NMR of the motifs that interact with the apo- and holoenzymes in solution.

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“…Deuterated trehalose was produced by the National Deuteration Facility, ANSTO. This was achieved by catalytic exchange reactions following a procedure of Koch and Stuart using a Raney nickel catalyst [39,40]. Isotopic purity, determined by mass spectrometry and solution NMR, was 67.8% of the 14 non-exchangeable hydrogens in the trehalose molecule.…”

Section: Methodsmentioning

confidence: 99%

Localization of trehalose in partially hydrated DOPC bilayers: insights into cryoprotective mechanisms

Kent

Hunt

Darwish

et al. 2014

J. R. Soc. Interface.

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Trehalose, a natural disaccharide with bioprotective properties, is widely recognized for its ability to preserve biological membranes during freezing and dehydration events. Despite debate over the molecular mechanisms by which this is achieved, and that different mechanisms imply quite different distributions of trehalose molecules with respect to the bilayer, there are no direct experimental data describing the location of trehalose within lipid bilayer membrane systems during dehydration. Here, we use neutron membrane diffraction to conclusively show that the trehalose distribution in a dioleoylphosphatidylcholine (DOPC) system follows a Gaussian profile centred in the water layer between bilayers. The absence of any preference for localizing near the lipid headgroups of the bilayers indicates that the bioprotective effects of trehalose at physiologically relevant concentrations are the result of non-specific mechanisms that do not rely on direct interactions with the lipid headgroups.

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The catalytic C-deuteration of some carbohydrate derivatives

Cited by 48 publications

References 19 publications

Invisible detergents for structure determination of membrane proteins by small‐angle neutron scattering

Invisible detergents for structure determination of membrane proteins by small‐angle neutron scattering

Studies of the Binding of Modest Modulators of the Human Enzyme, Sirtuin 6, by STD NMR

Localization of trehalose in partially hydrated DOPC bilayers: insights into cryoprotective mechanisms

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