Structural Variations of N‐Acetylneuraminic Acid, 11, Synthesis of the 4‐Methylumbelliferyl 2α‐Glycosides of 7‐Epi‐, 8‐Epi‐, and 7,8‐Bis(epi)‐N‐acetylneuraminic Acids, as well as of 7‐Deoxy‐, 8‐Deoxy‐, 9‐Deoxy‐, and 4,7‐Dideoxy‐N‐acetylneuraminic Acids and Their Behaviour Towards Sialidase from Vibrio cholerae

Zbiral, E.; Schreiner, Erwin; Salunkhe, M. M.; Schulz, Gerhard; Kleineidam, Reinhard G.; Schauer, Roland

doi:10.1002/jlac.198919890192

Cited by 20 publications

(8 citation statements)

References 27 publications

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“…In contrast with the influenza neuraminidase, little structural information is available on the Vibrio cholerae enzyme, although crystals suitable for X-ray crystallography have been grown (Taylor et al, 1992) and the enzyme has been cloned and expressed in Escherichia coli (Vimr et al, 1988). The V. cholerae enzyme, though, has been the subject of extensive synthetic organic chemically based studies of substrate specificity (Zbiral et al, 1989;Schreiner et al, 1991) and inhibitor power (Wallimann and Bernet et al, 1990;Czollner et al, 1990;Vasella and Wyler, 1991).…”

Section: Introductionmentioning

confidence: 99%

A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase

Guo

Sinnott

1993

Biochemical Journal

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Michaelis-Menten parameters for hydrolysis of seven aryl N-acetyl alpha-D-neuraminides by Vibrio cholerae neuraminidase at pH 5.0 correlate well with the leaving-group pKa (delta pK 3.0; beta 1g (V/K) = -0.73, r = -0.93; beta 1g (V) = -0.25; r = -0.95). The beta-deuterium kinetic-isotope effect, beta D2(V), for the p-nitrophenyl glycoside is the same at the optimum pH of 5.0 (1.059 +/- 0.010) as at pH 8.0 (1.053 +/- 0.010), suggesting that isotope effects are fully expressed with this substrate at the optimum pH. For this substrate at pH 5.0, leaving group 18O effects are 18(V) = 1.040 +/- 0.016 and 18(V/K) = 1.046 +/- 0.015, and individual secondary deuterium effects are beta proRD(V) = 1.037 +/- 0.014, beta proSD(V) = 1.018 +/- 0.015, beta proRD(V/K) = 1.030 +/- 0.017, beta proSD(V/K) = 1.030 +/- 0.017. All isotope effects, and the beta 1g(V/K) value are in accord with the first chemical step being both the first irreversible and the rate-determining step in enzyme turnover, with a transition state in which there is little proton donation to the leaving group, the C-O bond is largely cleaved, there is significant nucleophilic participation, and the sugar ring is in a conformation derived from the ground-state 2C5 chair. The apparent conflict between the beta 1g (V) value of -0.25 with all the kinetic-isotope-effect data can be resolved by the postulation of an interaction between the pi system of the aglycone ring and an anionic or nucleophilic group on the enzyme.

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Section: Introductionmentioning

confidence: 99%

A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase

Guo

Sinnott

1993

Biochemical Journal

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“…Changing the promotor to dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST, Entry 4), resulted in the formation of the glycal side product (18) with only trace quantities of 17α observable by NMR. However, activating the glycosylation reaction using NIS/AgOTf at -40 °C gave more promising results (entry 5) with a respectable yield of 72% and a slight preference for the α-anomer 17α.…”

Section: Resultsmentioning

confidence: 99%

“…Additionally, the chemistry of 4methylumbelliferyl sialic glycosides has been left unexplored for many years despite existing synthetic routes suffering from poor yields, low stereoselectivity and formation of the undesired glycal side product. [18][19][20][21] To this end, we report herein synthetic strategies to access C-5 derivatised neuraminic acid substrates with a fluorogenic 4-methylumbelliferyl (4-Mu) aglycone functionality in both anomeric configurations as tools to probe sialidase activity and specificity.…”

Section: Introductionmentioning

confidence: 99%

Facile Anomer-oriented Syntheses of 4-Methylumbelliferyl Sialic Acid Glycosides

Hassan¹,

Oscarson²

2021

Preprint

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As part of a program to find new sialidases and determine their enzymatic specificity and catalytic activity, a library of 4-methylumbelliferyl sialic acid glycosides derivatised at the C-5 position were prepared from N-acetylneuraminic acid. Both α- and β-4-methylumbelliferyl sialic acid glycosides were prepared in high yields and excellent stereoselectivity. Alpha anomers were accessed via reagent control by utilising additive CH3CN and TBAI, whereas the beta anomers were synthesised through a diastereoselective addition reaction of iodine and the aglycone to the corresponding glycal followed by reduction of the resulting 3-iodo compounds. Both anomer-oriented synthetic pathways allow for gram-scale stereoselective syntheses of the desired C-5 modified neuraminic acid derivatives for use as tools to quantify the enzymatic activity and substrate specificity of known sialidases, and potential detection and investigation of novel sialidases.

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“…This approach was extended to more complex 4-methylumbelliferyl fluorogenic glycosides, such as di-, triand oligosaccharides [62][63][64][65][66][67], and challenging monosaccharides such as sialic acids [68][69][70]. 4-Methylumbelliferyl aglycone analogues were also explored to better suit the properties of glycosidases [71][72][73][74].…”

Section: Fluorogenic Glycosidase Substratesmentioning

confidence: 99%

Fluorescently labelled glycans and their applications

Yan

Yalagala

Yan³

2015

Glycoconj J

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This review summarises the literature on the synthesis and applications of fluorescently labelled carbohydrates. Due to the sensitivity of fluorescent detection, this approach provides a useful tool to study processes involving glycans. A few general categories of labelling are presented, in situ labelling of carbohydrates with fluorophores, fluorescently labelled glycolipids, fluorogenic glycans, pre-formed fluorescent glycans for intracellular applications, glycan-decorated fluorescent polymers, fluorescent glyconanoparticles, and other functional fluorescent glycans.

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Cited by 20 publications

References 27 publications

A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase

A kinetic-isotope-effect study of catalysis by Vibrio cholerae neuraminidase

Facile Anomer-oriented Syntheses of 4-Methylumbelliferyl Sialic Acid Glycosides

Fluorescently labelled glycans and their applications

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