Evidence for a (1→4)-linked 4-O-(α-L-idopyranosyluronic acid 2-sulfate)-(2-deoxy-2-sulfoamino-D-glucopyranosyl 6-sulfate) sequence in heparin

Perlin, Arthur S.; Mackie, David M.; Dietrich, Carl P.

doi:10.1016/s0008-6215(00)80341-9

Cited by 136 publications

(43 citation statements)

References 23 publications

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“…In other experiments, M-Il was obtained by lyophilization of a solution of sodium heparin (40 mg) in either 0.05 N, 0.1 N, or 1 N sodium hydroxide (10 mL), followed by the removal of excess base with ion-exchange resin, or by dialysis. The product was pale yellow, suggesting that some elimination had also occurred, a possibility reinforced (33) by the presence of the olefinic doublet at 6 5.8.…”

Section: Methodsmentioning

confidence: 99%

Novel regio- and stereoselective modifications of heparin in alkaline solution. Nuclear magnetic resonance spectroscopic evidence

Jaseja¹,

Rej²,

Sauriol³

et al. 1989

Can. J. Chem.

131

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MAHESH JASEJA, RABINDRA N. REJ, FRANCOIS SAURIOL, and ARTHUR S. PERLIN. Can. J. Chem. 67, 1449 (1989).Nuclear magnetic resonance spectroscopic evidence is presented in characterizing three new structurally modified forms of heparin. One of these, polymer M-I, represents a conversion of about two-thuds of the a-L-iduronic acid 2-sulfate residues (1) into residues of a 2,3-anhydro derivative (3), through the action of sodium hydroxide. The formation of 3 is attributed to a base-catalysed displacement of the sulfate group of 1 by an intramolecular attack of 0 -3 on C-2. In more concentrated sodium hydroxide solution, heparin is transformed almost quantitatively into polymer M-11, which differs from it in having residues of (non-sulfated) a-L-iduronic acid (4) in place of 1. It is likely that 3 is an intermediate, and that a selective nucleophilic attack of hydroxide ion at C-2 accounts for the ido configuration in 4. The third modification, giving polymer M-111, is induced when a neutral or weakly alkaline solution of M-I is heated at 70°C or above, which promotes a different stereochemistry in the hydrolysis of the 2,3-oxirane ring of 3. Hence, in contrast to residues of 4 in M-11, most of the uronic acid residues of M-I11 appear to have the alternate, a-L-galacto, configuration. As shown by a comparison of beef lung and hog mucosal heparin, the rate at which M-I is converted into M-111 is facilitated by the higher level of structural heterogeneity in the mucosal heparin. Whereas the formation of M-I, -II, and -1II is accompanied by only moderate depolymerization, these novel polymers retain little of the anti-coagulant and anti-XA activities of the unmodified heparin.Key words: NMR spectroscopy, heparin, desulfation, anhydroaldoside, base-catalysed displacement. On prCsente les spectres de rdsonance magnCtique nuclCaire de trois nouvelles formes d'hCparine modifiCes structuralement. Dans l'une d'elles, le polymkre M-I, environ les deux tiers des rCsidus sulfates de I'acide a-L-iduronique (1) ont Ct C transformCs en rCsidu du dCrivC dthydro-2,3 (3) sous I'action de l'hydroxyde de sodium. On attribue la formation du dCrivC 3 au dCplacement, catalysk par une base, du groupe sulfate du composC 1 par suite d'une attaque intramolCculaire de I'oxygkne en position 3 (0-3) sur le carbone en position 2 (C-2). Dans une solution plus concentrke d'hydroxyde de sodium, I'hCparine se transforme presque quantitativement en polymkre M-11 qui difEre de I'hCparine par la prksence de rksidus (non sulfatks) de l'acide a-L-iduronique (4) au lieu du composC 1. I1 est comrnunCment admis que le compost! 3 est un intermkdiaire, et qu'une attaque nucltophile sklective de I'ion hydroxyde en C-2 est responsable de la configuration ido dans le composC 4. La troisikme modification, conduisant au polymkre M-111, est obtenue par chauffage B 70°C ou au-dessus d'une solution neutre ou faiblement alcaline du polymkre M-I, ce qui favorise une sterkochimie diffkrente dans I'hydrolyse du cycle oxyrane-2,3 du compost 3. Cependant, contrairement au rCsi...

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Section: Methodsmentioning

confidence: 99%

Novel regio- and stereoselective modifications of heparin in alkaline solution. Nuclear magnetic resonance spectroscopic evidence

Jaseja¹,

Rej²,

Sauriol³

et al. 1989

Can. J. Chem.

131

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“…The main repeating structure of heparin was established as a disaccharide of alternating N -and 6-O-sulfated α-D-glucosamine and 2-Osulfated α-L-iduronic acid (Perlin et al 1971), with a minor proportion of N -acetyl glucosamine and β-D-glucuronic acid. (Figs.…”

Section: Heparin and Antithrombinmentioning

confidence: 99%

The specificity of interactions between proteins and sulfated polysaccharides

Mulloy

2005

An. Acad. Bras. Ciênc.

107

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Sulfated polysaccharides are capable of binding with proteins at several levels of specifi city. As highly acidic macromolecules, they can bind non-specifi cally to any basic patch on a protein surface at low ionic strength, and such interactions are not likely to be physiologically signifi cant. On the other hand, several systems have been identifi ed in which very specifi c substructures of sulfated polysaccharides confer high affi nity for particular proteins; the best-known example of this is the pentasaccharide in heparin with high affi nity for antithrombin, but other examples may be taken from the study of marine invertebrates: the importance of the fi ne structure of dermatan sulfate (DS) to its interaction with heparin cofactor II (HCII), and the involvement of sea urchin egg-jelly fucans in species specifi c fertilization. A third, intermediate, kind of specifi c interaction is described for the cell-surface glycosaminoglycan heparan sulfate (HS), in which patterns of sulfate substitution can show differential affi nities for cytokines, growth factors, and morphogens at cell surfaces and in the intracellular matrix. This complex interplay of proteins and glycans is capable of influencing the diffusion of such proteins through tissue, as well as modulating cellular responses to them.

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“…B. Purves Scholarship Holder, 1970-1971 3Harold Hibbert Memorial Fellow, 1967-1968 side (I), in terms of replacement of a hydrogen atom by deuterium (9,12,13). That is, Hs is designated as the p r o 3 hydrogen (deuterium in this position would confer an S configuration upon the carbinol group as in 2) and H,, the pro-R hydrogen as in the R diastereomer 3.…”

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confidence: 99%

Stereochemistry of Dehydrogenation by D-Galactose Oxidase

Maradufu¹,

Cree²,

Perlin³

1971

Can. J. Chem.

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The stereochemistry of dehydrogenation of the primary carbinol group of D-galactose by D-galactose oxidase has been determined. Using D-galactose-6-d and methyl 13-D-galactopyranoside-6-d, it has been established that the reaction involves removal of thepro-S 6-hydrogen atom. This conclusion is based on product analysis, and on the relative impact of the deuterium isotope effect on oxidation rates of substrates having different R : S deuteration patterns. The absolute configurations at C-6 of these substrates have been determined by selective chemical transformations to products of known configuration. The rotational conformation of the 6-carbinol group of D-galactose and its possible relationship to the specificity of the enzyme are discussed, as well as the stereochemistry of reductive deuteration of aldehydo sugar derivatives.On a dktermink la stkrkochirnie de deshydrogknation du groupement carbinol primaire du D-galactose par le D-galactose oxydase. I1 a dtk Btabli, en utilisant le D-galactose-6-d et le mkthyl f3-D-galactopyranoside-6-d, que la rkaction implique le depart de I'atome d'hydrogene-6pro-S. Cette conclusion se base sur le produit d'analyse et sur l'impact relatif de I'effet de I'isotope deuterium sur les vitesses d'oxydation des substrats ayant des modeles diffkrents de deutkration R:S. Les configurations absolues en C-6 de ces substrats ont ktk dkterminees par des transformations chimiques selectives en produits de configuration connue. La conformation rotationnelle des groupements carbinole-6 du D-galactose et sa relation possible avec la sptcificite de I'enzyme sont discutkes, de mdme que la stkrkochimie de deuteration reductive des derivks alddhydo des sucres.

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Evidence for a (1→4)-linked 4-O-(α-L-idopyranosyluronic acid 2-sulfate)-(2-deoxy-2-sulfoamino-D-glucopyranosyl 6-sulfate) sequence in heparin

Cited by 136 publications

References 23 publications

Novel regio- and stereoselective modifications of heparin in alkaline solution. Nuclear magnetic resonance spectroscopic evidence

Novel regio- and stereoselective modifications of heparin in alkaline solution. Nuclear magnetic resonance spectroscopic evidence

The specificity of interactions between proteins and sulfated polysaccharides

Stereochemistry of Dehydrogenation by D-Galactose Oxidase

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