Heparan sulfate and heparin

There are quantitative differences in the chemical constitution of heparan sulfate and heparin polysaccharides, but qualitative differences in their biological location and core protein. Heparin is biosynthesised only in connective tissue mast cells and attached only to a unique protein core (serglycin). The initial polysaccharide chains have a DP (dimer) of 25(T400, but can be cleaved subsequently to give an array of heparin polysaccharides. Heparan sulfate, by contrast, can be synthesised on an array of proteins in various cells, with two major subfamilies of heparan sulfate proteoglycans, the syndecans and glypi-cans, which carry fewer and shorter polysaccharide chains. 

In order to identify the new reducing end, the products from nitrous acid treatment are reduced by NaB H4. Cleavage at both iV-acetyl and VV-sulfato sites can be achieved by initial de-VV-acetylation with hydrazine (at pH 4.0) prior to nitrous acid treatment. The combined treatment yields only disaccharides, but the 0-sulfation pattern is preserved. 

There are now many X-ray crystal structures of proteins complexed with heparin fragments. Despite the possibility of distortion from the free solution conformation by interaction of the protein, in fact the points for the cx-d-GlcNSp(6S)-(l- 4)-cx-L-IdoAp(2S) glycosidic link on the pseudo-Ramachandran 

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Stnictures 1. Characteristic structural motifs in heparan sulfate and heparin... 

Heparinoid polysaccharides such as heparan sulfate and heparin are able to interact with numerous proteins and influence vital biological processes. Heparinoid mimetics were prepared to reduce the structural complexity of heparinoids and to obtain selectivities. This article summarizes the development of heparinoid mimetics of different classes including representative syntheses and biological activities. Largely simplified compounds with regard to structure and synthetic access are described which maintain or exceed the activity of heparinoid polysaccharides. One of the recipes to increase binding or modify pharmacokinetic parameters was the introduction of hydrophobic groups. 

Subsequent modifications of the polymers involve extensive formation of O-sulfate esters,1903 193 197 N-deacetylation and N-sulfation,198/199 and epimerization at C5.10 In some tissues almost all GluA is epimer-ized.200 The modifications are especially extensive in dermatan, heparan sulfates, and heparin (see also p. 177).196 201 203b The modifications are not random and follow a defined order. N-Deacetylation must precede N-sulfation, and O-sulfation is initiated only after N-sulfation of the entire chain is complete. The modifications occur within the Golgi (see Fig. 20-7) but not all... 

In the following, we summarize briefly findings on the CPL fragments from dermatan sulfate, chondroitin sulfate, heparan sulfate, and heparin. 

Oligosaccharide Fragments Isolated from the Carbohydrate-Protein Linkage-Region of Heparan Sulfate and Heparin Proteoglycans... 

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.

CIONS is also found. Although heparan sulfate and heparin are structurally similar one should keep in mind that both are found on different core proteins. 

The ido configuration is present, isolated in the middle of other monosaccharide residues, in the polycondensed chains called glycosaminoglycans of natural polysaccharides dermatan sulfate, heparan sulfate, and heparin. The derivative in question belonging to the L-series is 2-0-sulfo-L-iduronic acid. It is represented (2.34, R = R = H) in a non-conformational manner with the a-L-idopyrano configuration present in these polysaccharides. The L-ido residue is isolated in the sequence, in the centre of the chains attached to 0-1 and 0-4, respectively (Section 17.3). It is found as a mixture of the l- C4 (2.35) and l- Sq (2.36) conformations. The proportion of the skew form varies from 40 to 60% according to the attached oligosaccharide sequences, R and R (Casu et al. 1986). 

Fig. 2. Typical oligosaccharide structures of heparan sulfate and heparin.

Heparan sulfate and heparin are GAGs that are present in a variety of tissues throughout the body, regulate many processes, and bind a variety of proteins or growth factors. There are several growth... 

Hyaluronic acid (HA), a high molecular weight (MW) biopolysaccharide, was discovered by Meyer and Palmer in 1934 in the vitreous humour of cattle eyes [2]. HA is a member of a group of similar polysaccharides that have been termed connective tissue polysaccharides , mucopolysaccharides , or glycosaminoglycans . These polysaccharides include chondroitin sulfate, dermatan sulfate, keratan sulfate, heparan sulfate, and heparin. HA is a... 

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