Heparin, disaccharide, structure

Fig. 2.5. Interactions of chemokines with heparin disaccharides. (A to C) Monomeric forms of chemokines are displayed as cartoons with residues found to interact with heparin colored red. (A) Monomer of crystal structure of CCL5 (RANTES) with heparin disaccharide I-S bound (red). (B) CXCL4 (PF4) with low-molecular-weight heparin (MW <9000d). (C) CXCL8 with heparin disaccharide I-S. (D) CXCL12 (SDF-la) with heparin disaccharide I-S. (E) CCL2, human IP-10, with conserved residues from murine IP-10 highlighted.

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 48-9. Structure of heparin. The polymer section illustrates structural features typical of heparin however, the sequence of variously substituted repeating disaccharide units has been arbitrarily selected. In addition, non-O-sulfated or 3-0-sulfated glucosamine residues may also occur. (Modified, redrawn, and reproduced, with permission, from Lindahl U et al Structure and biosynthesis of heparin-like polysaccharides. Fed Proc 1977 36 19.)...

Shaw JP, Johnson Z, Borlat F, et al. The X-ray structure of RANTES heparin-derived disaccharides allows the rational design of chemokine inhibitors. Structure (Cambridge) 2004 12 2081-93. 

Both positional linkages (uronic acid to hexosamine and hexosamine to uronic acid) were established as being (1 — 4) by structural analysis of the previously mentioned (see Section IV), crystalline disaccharides containing D-glucuronic acid, isolated from an acid hydrolyzate of carboxyl-reduced heparin.128-129 Further evidence was obtained from the structure of the D-glucuronic acid-containing counterpart of disaccharides 6 and 8, obtained as minor products from pig-mucosal heparin following nitrous acid deamination,1110 136-138 and acid hydrolysis followed by N-acetylation,130 respectively. 

Whereas the configuration at C-l of the amino sugar units in heparin was established as a-D by early studies, especially the structural characterization129 of crystalline disaccharide 9, the configuration of the D-glucuronic acid has been the subject of controversy. It was originally presumed to be a-D, on the basis of the structure proposed for a disaccharide obtained, in addition to 9, from desulfated, carboxyl-reduced heparin.129... 

Fig. 2 Structures of the major and minor disaccharide sequences of heparin and heparan sulfate as well as the major disaccharide units of chondroitin sulfate, dermatan sulfate, keratan sulfate, and hyaluronic acid, where Ac is acetyl.

After hydrolysis of carboxyl-reduced and partially desulfated heparin with hydrochloric acid, Wolfrom and coworkers117 isolated a disaccharide that was identified118 as 2-amino-2-deoxy-4-0-a-D-glucopyran-osyl-D-glucopyranose ( maltosamine ) hydrochloride, which gave a crystalline N-acetyl derivative (50). This structure was subsequently... 

An understanding of the structures of the molecules of heparin and heparan sulfate has come, in part, from studies with degradative enzymes, but also with biosynthetic enzymes. Both polysaccharides are based on the disaccharide unit which, in the initial stage of biosynthesis, consists of... 

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.

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