- Glycoside cleavage by a new mechanism in unsaturated glucuronyl hydrolases
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Unsaturated glucuronyl hydrolases (UGLs) from GH family 88 of the CAZy classification system cleave a terminal unsaturated sugar from the oligosaccharide products released by extracellular bacterial polysaccharide lyases. This pathway, which is involved in extracellular bacterial infection, has no equivalent in mammals. A novel mechanism for UGL has previously been proposed in which the enzyme catalyzes hydration of a vinyl ether group in the substrate, with subsequent rearrangements resulting in glycosidic bond cleavage. However, clear evidence for this mechanism has been lacking. In this study, analysis of the products of UGL-catalyzed reactions in water, deuterium oxide, and dilute methanol in water, in conjunction with the demonstration that UGL rapidly cleaves thioglycosides and glycosides of inverted anomeric configuration (substrates that are resistant to hydrolysis by classical glycosidases), provides strong support for this new mechanism. A hydration-initiated process is further supported by the observed UGL-catalyzed hydration of a C-glycoside substrate analogue. Finally, the observation of a small β-secondary kinetic isotope effect suggests a transition state with oxocarbenium ion character, in which the hydrogen at carbon 4 adopts an axial geometry. Taken together, these observations validate the novel vinyl ether hydration mechanism and are inconsistent with either inverting or retaining direct hydrolase mechanisms at carbon 1.
- Jongkees, Seino A. K.,Withers, Stephen G.
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- Indium-Mediated Coupling of α-(Bromomethyl)acrylic Acid with Carbonyl Compounds in Aqueous Media. Concise Syntheses of (+)-3-Deoxy-D-glycero-D-galacto-nonulosonic Acid and N-Acetylneuraminic Acid
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Indium mediates the coupling of α-(bromomethyl)acrylic acid with carbonyl compounds in aqueous media to give the corresponding γ-hydroxy-α-methylene carboxylic acids.The reaction has been applied to the syntheses of (+)-3-deoxy-D-glycero-D-galacto-nonulos
- Chan, Tak-Hang,Lee, Ming-Chao
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- A Concise Chemical Synthesis of (+)-3-Deoxy-D-glycero-D-galacto-nonulosonic acid (KDN)
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The sialic acid KDN is synthesized stereoselectively in three steps from D-mannose by taking advantage of an indium mediated coupling reaction in aqueous medium.
- Chan, Tak-Hang,Li, Chao-Jun
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- The Use of an Immobilized Aldolase in the First Synthesis of a Natural Deaminated Neuraminic Acid
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The first synthesis of 3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN) (1) was achieved by condensation of the non-nitrogeneous substrate D-mannose (2) with pyruvate, catalysed by immobilized acylneuraminate pyruvate lyase.
- Auge, Claudine,Gautheron, Christine
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- Microbial glycosyltransferases for carbohydrate synthesis: α-2,3-sialyltransferase from Neisseria gonorrheae
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The α-2,3-sialyltransferase from Neisseria gonorrheae was overproduced in E. coli for exploitation of its substrate specificity and synthetic utility. Several potential acceptor substrates were synthesized in this study, including mono- and oligosaccharid
- Izumi,Shen,Wacowich-Sgarbi,Nakatani,Plettenburg,Wong
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p. 10909 - 10918
(2007/10/03)
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- Indium-mediated chain-extension: An improved protocol for the concise, diastereospecific synthesis of KDN and other sialic acids
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Aqueous indium-mediated allylation of D-mannose with ethyl 2- (bromomethyl)acrylate leads, under acidic conditions, exclusively to the threo products in high yields. A new purification procedure for indium- mediated reactions has been developed which is based on a simple precipitation of indium-containing phosphate salts. This simplified protocol leads directly to diastereomerically pure KDN and other sialic acids, thus obviating the need for the usual lengthy purification procedures.
- Warwel, Mathias,Fessner, Wolf-Dieter
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p. 865 - 867
(2007/10/03)
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- First total synthesis of (+)-3-deoxy-D-glycero-D-galacto-2-nonulosonic acid (KDN) from a non-carbohydrate source
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Enantiopure cis-1,2-dihydrocatechol 2, a product obtained by microbial oxidation of chlorobenzene, has been converted into KDN 1 via a ten step reaction sequence.
- Banwell, Martin,De Savi, Chris,Watson, Keith
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p. 1189 - 1190
(2007/10/03)
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- Installation of the pyruvate unit in glycidic aldehydes via a Wittig olefination-Michael addition sequence utilizing a thiazole-armed carbonyl ylid. A new stereoselective route to 3-deoxy-2-ulosonic acids and the total synthesis of DAH, KDN, and 4-epi-KDN
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A method for the installation of the (2-thiazolylcarbonyl)methylene group, i.e. a masked pyruvate unit owing to the thiazole to formyl equivalence, in sugar-derived aldehydes has been developed. The strategy involves stereoselective carbon-carbon and carb
- Dondoni, Alessandro,Marra, Alberto,Merino, Pedro
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p. 3324 - 3336
(2007/10/02)
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- Overproduction of CMP-sialic acid synthetase for organic synthesis
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The gene coding for Escherichia coli CMP-sialic acid synthetase (E.G. 2.7.7.43) was cloned and overexpressed in E. coli through a primer-directed polymerase chain reaction. Two plasmids were constructed to produce the native enzyme and a modified enzyme f
- Liu, Jennifer Lin-Chun,Shen, Gwo-Jenn,Ichikawa, Yoshitaka,Rutan, James F.,Zapata, Gerardo,Vann, Willie F.,Wong, Chi-Huey
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p. 3901 - 3910
(2007/10/02)
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- SCOPE AND LIMITATIONS OF THE ALDOL CONDENSATION CATALYZED BY IMMOBILIZED ACYLNEURAMINATE PYRUVATE LYASE
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New substrates have been used in the aldol condensation catalyzed by immobilized acylneuraminate pyruvate lyase: hexoses 3, 4, 7, 8 and pentoses 2, 5, 6.Condensation of pyruvate with 2-5, 7 and 8 led to pure compounds related to 3-deoxy-D-glycero-D-galacto-nonulosonic acid (KDN).Surprisingly, condensation with D-arabinose 6 gave a mixture of diastereomers, 3-deoxy-α-D-manno-2-octulosonic acid (KDO) and 4-epi KDO.
- Auge, Claudine,Bouxom, Benedicte,Cavaye, Bertrand,Gautheron, Christine
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p. 2217 - 2220
(2007/10/02)
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- IMPROVED SYNTHESES OF TWO 3-DEOXYALD-2-ULOSONIC ACIDS(KDN,KDO) BY CONDENSATION OF OXALACETIC ACID WITH ALDOSES FOLLOWED BY Ni2+CATALYZED DECARBOXYLATION
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Condensation of oxalacetic acid with D-mannose and D-arabinose followed by Ni2+catalyzed decarboxylation gave 3-deoxy-D-glycero-D-galacto-2-nonulosonic acid(KDN) and 3-deoxy-D-manno-2-octulosonic acid(KDO) respectively in high chemical yield and high diastereoselectivity.
- Shirai, Ryuichi,Ogura, Haruo
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p. 2263 - 2264
(2007/10/02)
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- Studies on Sialic Acids. XV. Synthesis of α- and β-O-Glucosides of 3-Deoxy-D-glycero-D-galacto-2-nonulopyranosonic Acid (KDN)
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3-Deoxy-D-glycero-D-galacto-2-nonulopyranosonic acid (KDN) was synthesized by base-catalyzed condensation in good yield.Furthermore, benzyl (methyl 3-deoxy-D-glycero-α-D-galacto-2-nonulopyranosid)onate and sodium 2-(5-cholesten-3β-yloxy)-3-deoxy-D-glycero
- Nakamura, Mitsunobu,Furuhata, Kimio,Ogura, Haruo
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p. 4807 - 4813
(2007/10/02)
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