Heparin, structure

R. A. Bradshaw and S. Wessler (Eds.), Heparin Structure, Function, and Clinical Implications, Plenum Press, New York, 1975. 

Deamination studies have aided attempts to locate the positions of the O-sulfate groups in heparin. From the results of deamination and periodate-oxidation studies, it was concluded239 that half of the uronic acid residues are sulfated at C-2, and sequential periodate oxidation, reduction with sodium borohydride, acid treatment, and deamination gave 2,5-anhydro-D-mannose 6-sulfate.240,241 Sulfated O-(hexosyluronic acid)-2,5-anhydro-D-mannose and sulfated uronic acids were subsequently isolated, and the isolation (in 65% yield) of the disulfated 0-(idosyluronic acid)-2,5-anhydro-D-mannose (137) from heparin, together with the 13C n.m.r. spectra of 137 and heparin, suggested243 that at least two thirds of the heparin structure consists of the repeating unit 138. 

A similar situation exists with the K5 antigen. Figure 15 shows that this capsular polysaccharide is practically identical with a precursor of heparin. It was in fact shown recently that the K5 polysaccharide is a substrate for the de-N-acetylase which initiates the processing of this precursor to heparin. Structural relatedness may not be the only cause for the very low immunogenicity of a coli capsular antigen, but it appears quite suggestive. 

Faham S, Hileman RE, Fromm JR, Linhardt RJ, Rees DC, Heparin structure and interactions with basic fibroblast growth factor. Science I 996 271 (5252) I I I 6-1 120. 

S. Faham, R. E. Hileman, J. R. Fromm, R. J. Linhardt, and D. C. Rees. Heparin structure and mteractions with basic fibroblast growth factor. Science, 271 ( 5252), 1116-1120, 1996. 

In the chemical literature prior to 1940, the majority of papers published on heparin were devoted to the isolation and purification of the polysaccharide. The earliest workers were concerned with the isolation of highly active, non-toxic preparations. Later, as attention was focused on the problem of heparin structure, many further attempts were made to isolate the pure substance, and extensive data on the activity and analytical composition of the various preparations have consequently accumulated. During the early period, the different research laboratories each claimed to have isolated pure heparin, but it is only within the last decade, with the application of physicochemical methods, that relatively homogeneous preparations have become available. 

Linhardt RJ. Perspective 2003 Claude S. Hudson award address in carbohydrate chemistry. Heparin structure and activity. J Med Chem 2003 46 2551-2554. 

Johnson DJ, Li W, Adams TE, Huntington JA. Antithrombin-S195A factor Xa-heparin structure reveals the allosteric mechanism of antithrombin activation. Embo J 2006 25 2029-2037. 

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