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Evaluation of critical groups required for the binding of heparin to antithrombin.

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Evaluation of critical groups required for the binding of heparin to antithrombin.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Atha, D. H. Stephens, A. W. Rosenberg, R. D.
Abstract	We have examined the quantitative importance of various monosaccharide residues of an octasaccharide domain of heparin that are responsible for the binding of this oligosaccharide to antithrombin. Different fragments of the octasaccharide were prepared by enzymatic digestion and the avidities of these oligosaccharides for antithrombin were determined by equilibrium dialysis. The data show that the non-reducing-end and the reducing-end tetrasaccharides contribute equally to the binding energy of the octasaccharide. The O6-sulfate group of the N-acetyl glucosamine moiety within the nonreducing-end tetrasaccharide is responsible for approximately equal to 45% of the binding energy of the octasaccharide. Neither the two non-sulfated uronic acid groups that flank this residue nor the N-sulfated glucosamine residue on the reducing end of this tetrasaccharide sequence that bears the unique O3-sulfate substituent contribute significantly to the binding energy of the octasaccharide. We suggest that the lack of sulfation of the two uronic acid moieties within the nonreducing-end tetrasaccharide may be required to permit the N-acetyl glucosamine O6-sulfate group to interact with a specific region on the antithrombin molecule. However, we cannot exclude the possibility that the O3-sulfate group plays an important role in orienting this O6-sulfate group within the nonreducing-end tetrasaccharide.
ISSN	00278424
e-ISSN	10916490
Journal	Proceedings of the National Academy of Sciences of the United States of America
Issue Number	4
Volume Number	81
Language	English
Publisher	National Academy of Sciences
Publisher Date	1984-04-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Antithrombins Metabolism Heparin Animals Chemical Phenomena Chemistry Kinetics Molecular Weight Structure-Activity Relationship Comparative Study Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Multidisciplinary
Content Type	Text
Resource Type	Article
Subject	Multidisciplinary

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