Structural parameters and natural occurrence of 2-deoxy-2, 3-didehydro-N-glycoloyneuraminic acid

Nöhle, Ulrich; Shukla, Ashok; Schröder, Cornelia; Reuter, Gerd; Schauer, Roland; Kamerling, Johannis P.; Vliegenthart, Johannes F.G.

doi:10.1111/j.1432-1033.1985.tb09219.x

Cited by 15 publications

(5 citation statements)

References 19 publications

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“…Another 10 modified forms are found in nature as derivatives of the 2,3-unsaturated sialic acid 2,3-dehydro-N-acetyl-D-neuraminic acid (Neu5Ac2en) [34,169,177]. Interestingly, Neu5Ac2en and its N-glycolyl derivative are very effective inhibitors of sialidases [178,179]. This sugar has been used as lead structure for computer-aided drug design of a potent inhibitor of…”

Section: Review Articlementioning

confidence: 99%

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Reuter¹,

Gabius²

1999

Cellular and Molecular Life Sciences (CMLS)

214

141

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Protein and lipid glycosylation is a ubiquitous phenomenon. The task of cataloguing the great structural variety of the glycan part has demanded considerable efforts over decades. This patient endeavor was imperative to discern the inherent rules of glycosylation which cannot affirm assumptions on a purely coincidental nature of this type of protein and lipid modification. These results together with theoretical considerations uncover a salient property of oligosaccharides. In comparison with amino acids and nucleotides, monosaccharides excel in their potential to serve as units of hardware for storing biological information. Thus, the view that glycan chains exclusively affect physiochemical properties of the conjugates is indubitably flawed. This original concept has been decisively jolted by the discovery of endogenous receptors (lectins) for distinct glycan epitopes which are as characteristic as a fingerprint or a signature for a certain protein (class) or cell type. Recent evidence documents that these binding proteins are even endowed with the capacity to select distinct low-energy conformers of the often rather flexible oligosaccharides, granting entry to a new level of regulation of ligand affinity by shifting conformer equilibria. The assessment of the details of this recognition by X-ray crystallography, nuclear magnetic resonance spectroscopy, microcalorimetry and custom-made derivatives is supposed to justify a guarded optimism in satisfying the need for innovative drug design in antiadhesion therapy, for example against viral or bacterial infections and unwanted inflammation. This review presents a survey of the structural aspects of glycosylation and of evidence to poignantly endorse the notion that carrier-attached glycan chains can partake in biological information transfer at the level of cell compartments, cells and organs.

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Section: Review Articlementioning

confidence: 99%

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Reuter¹,

Gabius²

1999

Cellular and Molecular Life Sciences (CMLS)

214

141

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“…N-Acetylneuraminate pyruvate-lyase was obtained from Wako Chemicals, Osaka. 2,3-Didehydro-2,3-dideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid (KDN2en), 2,3-didehydro-2,3,4-trideoxy-D-glycero-D-galacto-2-nonulopyranosonic acid (4-deoxy-KDN2en), and 2-deoxy-2,3-didehydro-N-glycolylneuraminic acid (Neu5Gc2en) were chemically synthesized according to literature procedures (25,27). 2 …”

Section: Chemicalsmentioning

confidence: 99%

Catalysis by a New Sialidase, Deaminoneuraminic Acid Residue-cleaving Enzyme (KDNase Sm), Initially Forms a Less Stable α-Anomer of 3-Deoxy-D-glycero-D-galacto-nonulosonic Acid and Is Strongly Inhibited by the Transition State Analogue, 2-Deoxy-2,3-didehydro-D-glycero-D-galacto-2-nonulopyranosonic Acid, but Not by 2-Deoxy-2,3-didehydro-N-acetylneuraminic Acid

Terada

Kitajima

Inoue

et al. 1997

Journal of Biological Chemistry

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Deaminoneuraminic acid residue-cleaving enzyme (KDNase Sm) is a new sialidase that has been induced and purified from Sphingobacterium multivorum. Catalysis by this new sialidase has been studied by enzyme kinetics and 1 H NMR spectroscopy. V max /K m values determined for synthetic and natural substrates of KDNase Sm reveal that 4-methylumbelliferyl-KDN (KDN␣2MeUmb, V max /K m ‫؍‬ 0.033 min ؊1 ) is the best substrate for this sialidase, presumably because of its good leaving group properties. The transition state analogue, 2,3-didehydro-2,3-dideoxy-D-galacto-D-glycero-nonulosonic acid, is a strong competitive inhibitor of KDNase Sm (K i ‫؍‬ 7.7 M versus K m ‫؍‬ 42 M for KDN␣2MeUmb). 2-Deoxy-2,3-didehydro-N-acetylneuraminic acid and 2-deoxy-2,3-didehydro-N-glycolylneuraminic acid are known to be strong competitive inhibitors for bacterial sialidases such as Arthrobacter ureafaciens sialidase; however, KDNase Sm activity is not significantly inhibited by these compounds. This observation suggests that the hydroxyl group at C-5 is important for recognition of the inhibitor by the enzyme.Reversible addition of water molecule (or hydroxide ion) to the reactive sialosyl cation, presumably formed at the catalytic site of KDNase Sm, eventually gives rise to two different adducts, the ␣-and ␤-anomers of free 3-deoxy-D-glycero-D-galacto-nonulosonic acid. 1 H NMR spectroscopic studies clearly demonstrate that the thermodynamically less stable ␣-form is preferentially formed as the first product of the cleavage reaction and that isomerization rapidly follows, leading to an equilibrium mixture of the two isomers, the ␤-isomer being the major species at equilibrium. Therefore, we propose that KDNase Sm catalysis proceeds via a mechanism common to the known exosialidases, but the recognition of the substituent at C-5 by the enzyme differs.

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“…636,637 A number of other naturally occurring sialic acids have also been synthesized along organic chemical or aldolase-catalyzed routes. Examples are as follows: Neu2en5Ac, 638 Neu2en5Gc, 75,638 Neu2en5,9Ac 2 , 56 Neu2en5, 7,9Ac 3 , 56 Neu2en9Ac5Gc, 56 Neu2en5GcAc, 56 Kdn, [639][640][641] Kdn2en, 642 Neu2, 7an5Ac, 643,644 Neu5Ac8Me, 645 Neu5Ac9P, 51 Neu5Ac1,7lactone, [646][647][648] Neu5Gc1,7lactone, 647 and Kdn1,7lactone. 647 See also refs.…”

Section: Growing Interest From the Organic And Enzymatic Chemistrymentioning

confidence: 99%

Exploration of the Sialic Acid World

Schauer

Kamerling

2018

Advances in Carbohydrate Chemistry and Biochemistry

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248

225

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The Sialic Acid World Table 1 Survey of Reported Structures of Naturally Occurring Members of the Sialic Acid Family-cont'd Name Abbreviation References5-N-Acetyl-8-O-acetyl-9-Olactyl-neuraminic acid Neu5,8Ac 2 9Lt 45 5-N-Acetyl-8-O-methylneuraminic acid Neu5Ac8Me 6,19,25,33,46 5-N-Acetyl-4-O-acetyl-8-Omethyl-neuraminic acid Neu4,5Ac 2 8Me 19 5-N-Acetyl-9-O-acetyl-8-Omethyl-neuraminic acid Neu5,9Ac 2 8Me 6,19,33,46 5-N-Acetyl-9-O-methylneuraminic acid Neu5Ac9Me 47 5-N-Acetyl-4-O-sulfoneuraminic acid Neu5Ac4S 48 5-N-Acetyl-8-O-sulfoneuraminic acid Neu5Ac8S 19,32,49,50 5-N-Acetyl-4-O-acetyl-8-Osulfo-neuraminic acid Neu4,5Ac 2 8S 19 5-N-Acetyl-9-O-phosphoneuraminic acid f,g Neu5Ac9P 51 5-N-Acetyl-2-deoxy-2,3didehydro-neuraminic acid g,h Neu2en5Ac 6,30,33,43,52-54 5-N-Acetyl-9-O-acetyl-2deoxy-2,3-didehydroneuraminic acid g Neu2en5,9Ac 2 55,56 5-N-Acetyl-2-deoxy-2,3didehydro-9-O-lactylneuraminic acid g Neu2en5Ac9Lt 55,565-N-Acetyl-2,7-anhydroneuraminic acid g,i

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Structural parameters and natural occurrence of 2-deoxy-2, 3-didehydro-N-glycoloyneuraminic acid

Cited by 15 publications

References 19 publications

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Eukaryotic glycosylation: whim of nature or multipurpose tool?

Exploration of the Sialic Acid World

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