N-Acetylgalactosamine 4,6-O-sulfate residues mediate binding and activation of heparin cofactor II by porcine mucosal dermatan sulfate

Glycobiology
Anna Margrét HalldórsdóttirDouglas M Tollefsen

Abstract

Dermatan sulfate (DS) accelerates the inhibition of thrombin by heparin cofactor II (HCII). A hexasaccharide consisting of three l-iduronic acid 2-O-sulfate (IdoA2SO3)-->N-acetyl-D-galactosamine 4-O-sulfate (GalNAc4SO3) subunits was previously isolated from porcine skin DS and shown to bind HCII with high affinity. DS from porcine intestinal mucosa has a much lower content of this disaccharide but activates HCII with potency similar to that of porcine skin DS. Therefore, we sought to characterize oligosaccharides from porcine mucosal DS that interact with HCII. DS was partially depolymerized with chondroitinase ABC, and oligosaccharides containing 2-12 monosaccharide units were isolated. The oligosaccharides were then fractionated by anion-exchange and affinity chromatography on HCII-Sepharose, and the disaccharide compositions of selected fractions were determined. We found that the smallest oligosaccharides able to bind HCII were hexasaccharides. Oligosaccharides 6-12 units long that lacked uronic acid (UA)2SO3 but contained one or two GalNAc4,6SO3 residues bound, and binding was proportional to both oligosaccharide size and number of GalNAc4,6SO3 residues. Intact DS and bound dodecasaccharides contained predominantly IdoA bu...Continue Reading

References

May 29, 1986·Biochemical and Biophysical Research Communications·M F ScullyV V Kakkar
Sep 6, 2002·Glycobiology·Janet M Trowbridge, Richard L Gallo
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Aug 19, 2004·Blood·Cristina P VicenteDouglas M Tollefsen

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Citations

Jan 5, 2010·Biological & Pharmaceutical Bulletin·Reiko Ishii-NozawaKoichi Takeuchi
Jan 10, 2014·Chemical Communications : Chem Comm·Jeyakumar KandasamyPeter H Seeberger
Mar 16, 2007·Comparative Biochemistry and Physiology. Part B, Biochemistry & Molecular Biology·Maisa L S SouzaLuiz-Claudio F Silva
Feb 28, 2013·The FEBS Journal·Martin A ThelinAnders Malmstrom
Aug 21, 2013·Molecular Genetics and Metabolism·Roger LawrenceJeffrey D Esko
Dec 30, 2006·Arteriosclerosis, Thrombosis, and Vascular Biology·Douglas M Tollefsen
Oct 15, 2013·American Journal of Clinical Pathology·Bettina KovácsLászló Muszbek

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