Heparin cleavage

VIII. Selective Cleavage of Heparin and Heparan Sulfate. 84... 

Conclusive evidence for the a-L configuration of the idosyluronic-to-hexosamine bond was provided by 1H-n.m.r. studies on disaccharide 7, obtained as the major product ( 75% yield) of the cleavage of heparin by heparinase.106 This configuration is consistent also with the 1H- and 13C-n.m.r. spectra of disaccharide 6 (the major product from nitrous acid cleavage of heparin103-106) and of unmodified heparin.82-84... 

Because of a supposedly statistical cleavage of the biosynthetic precursor of heparin, and uneven distribution of incompletely transformed residues (see Sections II and VI), chains that constitute conventional heparin differ from each other, both in average length and in sulfation pattern. 

Alkali-catalyzed cleavage of glycosidic bonds of glycosaminoglycur-onates occurs by way of -elimination.223 By proper choice of the experimental conditions, it seems possible to achieve a controlled degradation of heparin by -elimination, producing fragments apparently preserving... 

Fig. 5. —Tentative Model for a Heparin Chain Containing the Linkage Region. [1 and 2 are sites of cleavage with 2-pyridone, affording fragments A and B A may be further cleaved by a more drastic treatment. The active site for antithrombin is proposed - 8 to be within fragment A. ...

Scheme 3.—Exhaustive Cleavage of Heparin (Arbitrary Sequence) with Nitrous Acid.

Extracts of Flavobacterium heparinum that had been induced to grow on heparin-like polysaccharides contain a number of enzymes that may ultimately degrade heparin and heparan sulfate to monosaccharides.137,145 240 The enzymes that cause the primary cleavage of heparinlike chains are heparinase (EC 4.2.2.7) and heparanase (EC 4.2.2.8, formerly called heparitinase241,242). 

Scheme 5.—Typical Cleavage of Heparin (Arbitrary Sequence) with Heparinase (HEPase) and Heparanase (HSase). [Fragments longer than a tetrasaccharide may be obtained by separate use of each enzyme. The combined use of the two enzymes produces only disaccharides.]...

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