Heparin periodate oxidation

Periodate Oxidation of Heparin and Related Compounds, A. B. Foster, R. Harrison, T. D. Inch, M. Stacey, and J. M. Webber, Biochem. /., 80 (1961) 12P-13P (Proceedings of the Biochemical Society 405th Meeting at Univ. of Birmingham, April 28-29, 1961). 

In contrast to L-iduronic acid residues, most of which are sulfated at C-2, D-glucuronic acid residues in heparin and heparan sulfate are largely or exclusively nonsulfated. This was especially proved by their susceptibility to periodate oxidation,123 and through characterization of D-glucuronic acid-containing di- and tetra-saccharides from deamina-tive104 109 110 138 or heparinase - heparanase cleavage137,145 of heparin. 

Periodate oxidation was used in early work for obtaining information on the substitution pattern of heparin.1,100 102 In fully N-substituted (N-sulfated or N-acetylated, or both) glycosaminoglycans, the only bond susceptible to splitting by periodate is C-2-C-3 of unsubstituted uronic acid residues. As illustrated in Scheme 4 for heparin, only nonsulfated D-glucuronic acid and L-iduronic acid residues are split by periodate. 

Trifluoroacetic acid is volatile, and thus readily removed. This acid was used by Albersheim and coworkers for the hydrolysis of plant cell-walls,39 and has since been employed for cell walls,40-43 plant mucilages,44 blood-group oligosaccharides,45 peptidogalactoman-nans,46 heparin,47 and disaccharides in blood and urine.48,49 It has also been suggested as an alternative to 6 M hydrochloric acid in the determination of amino sugars,50 and for the hydrolysis of polyalcohols produced by periodate oxidation of polysaccharides.503 Lee... 

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. 

J13, Jorpes, J. E., Wemer, B., and Aberg, B., The fuchsin-sulphurous acid test after periodate oxidation of heparin and allied polysaccharides. ]. Biol. Chetn. 176, 277-282 (1948). 

Periodate oxidation was used in early work for obtaining information on the substitution pattern of heparin. In fully N-substituted (N-... 

L.-A. Fransson, Periodate oxidation of the D-glucuronic acid residues in heparan sulphate and heparin, Carbohydr. Res., 62 (1978) 235-244. 

Data obtained from n.m.r. analysis and from potentiometric titration of variously desulphated and periodate-oxidized heparins have supported the interpretation that non-sulphated cx-L-iduronate residues may adopt two ring conformations. The non-sulphated L-iduronic acid residues in heparin and heparin sulphate have been shown to be resistant to periodate oxidation at pH 3.0, under conditions which will oxidize a large proportion of the D-gluc-uronic acid residues. ... 

Studies of the periodate oxidation of heparin and of its product of degradation have also been used as a basis for proposing various chemical structures. The lack of precision of this method, and the erroneous conclusion derived from similar studies on other glycosaminoglycuronoglycans, render the structural allocation uncertain. The liberation of ammonia by periodate oxidation of an A -desulfated heparin suggests, however, the absence of linkage at position 3 of the glucosamine residue . ... 

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