Heparin repeating units

The interesting oligomers (28) containing "open-chain" uronic acid analogues were prepared by use of the pentenyl disaccharide analogue (27). The pentamer was converted into the polysulfate which is related to the heparin repeating unit. ... 

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. 

Disaccharides of the hexuronic acid-hexosamine type constitute the fundamental repeating unit of many mucopolysaccharides, from which they are derived by hydrolytic degradation. Further hydrolytic treatment results generally in destruction of the uronic acid moiety of the disaccharide. Structural studies have been made on the disaccharides from hyaluronic acid (hyalobiouronic acid), chondroitinsulfate (chondrosine), and heparin (heparosine). 

Figure 2. Structures of the glycosaminoglycans and their linkage regions to protein. Two disaccharide repeating units are shown to emphasize the microheterogeneity that exists in some cases. Heparan sulfate and heparin show many structural similarities. However, heparan sulfate contains more GlcNAc(a-1 — 4)GlcUA repeating units fewer glucosamine residues are N-sulfated, and few iduronic acid residues are sulfated at C2.

Heparin is particularly highly, though variably, sulfated. The repeating unit consists of D-gtocuronic or L-iduronic add linked to D-glucosamine — [hexuronic... 

Most of the polysaccharides of interest in this text are termed glycosaminoglycans, polymers that contain an amino sugar in the repeat unit. Glycosaminoglycans that are abundant in mammalian tissues include hyaluronan, chondroitin sulfate, dermatan sulfate, keratan sulfate, and heparin-heparan sulfate (see Table 2.4). Most of these glycosaminoglycans,... 

Knowledge of the chemical repeating pattern is a prerequisite to analysis of the diffraction patterns from polysaccharides. Among the complex polysaccharides studied thus far, heparin has presented the most problems. Nieduszynski and Atkins22 -24 previously interpreted the data by using a tetrasaccharide repeat unit for heparin they have now taken the repeat unit to be a disaccharide, composed of substituted 2-amino-2-deoxy-D-glucose and L-iduronate residues.25 In a re-... 

P. C. Wyss, J. Kiss, and W. Arnold, Synthesis of heparin saccharides IV, Synthesis of disaccharides possessing the structure of a repeating unit of heparin, Helv. Chim. Acta., 58 (1975) 1847-1864. 

Heteropolysaccharides are long-chain polymers that contain more than one type of monosaccharide, many of which are amino sugars. As a result, they are often referred to as gly-cosaminoglycans, which include chondroitm sulfate, hyaluronic acid, and heparin. Hyaluronic acid is abundant in the fluid of joints and in the vitreous humor of the eye. Chondroitin sulfate is an important component of cartilage and heparin has anticoagulant function. The structures of the repeat units of these polymers are shown below. 

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