Chondroitin derivatives

Danaparoid (Orgaran mean MW, 6,000 Da) is a mixture of nonheparin glycosaminoglycans derived from pig gut (dermatan sulfate, heparan sulfate, chondroitin sulfate). Die anti-Xa/anti-IIa ratio (22 1) is even greater than seen with LMWH. Die anti-IIa effect may be mediated in part by dermatan sulfate, which catalyzes thrombin inhibition by heparin cofactor II. 

The methylated derivatives served as the basis of elegant studies in which Jeanloz and his colleagues unequivocally established the structure of hyaluronan, dermatan sulfate, and the chondroitin sulfates. They also clarified many confusing issues, including the position of the sulfate groups in these polymers. In the course of this work, they proved that dermatan sulfate contained L-iduronic acid, a sugar not known before to occur in nature. 

The downfield displacement of the C-6 resonance of chondroitin on O-sulfation was 6.5 p.p.m., close to the 6.6 p.p.m. observed on 6-0-substitution of 3-D-glucose.152 As may be seen from Table VI, O-sulfation of a,j8-D-glucose and methyl 3-O-methyl-a-D-mannopyranoside153 causes a strong, downfield shift of the substituted resonance that is accompanied by smaller, upfield displacements of the signals of adjacent carbon atoms. Other, more-distant, substitution effects were not observed, except for the C-2 and OMe-3 signals on 4-O-sulfation of the D-mannopyranoside derivative. 

The phosphate esters and, to lesser extent, the sulphate esters of monosaccharides are very important naturally occurring derivatives. Metabolism of carbohydrates involves the formation and interconversion of a succession of monosaccharides and their phosphate esters of which glucose-1-phosphate and fruc-tose-6-phosphate are important examples. The sulphate esters of monosaccharides or their derivatives (usually esterified at carbon 6) are found in several polysaccharides, notably chondroitin sulphate, which is a constituent of connective tissues. 

Glucosamine is an amino sugar derivative occurring naturally in healthy tendons, ligaments and cartilage. Its use has been shown to be effective in the symptomatic relief of osteoarthritis, especially in combination with chondroitin, also a derivative of cartilage. 

Polysiloxanes are widely employed as biomaterials. Artificial skin can be fabricated from a bilayer fabricated from a cross-linked mixture of bovine hide, collagen, and chondroitin sulfate derived from shark cartilage with a thin top layer of polysiloxane. The polysiloxane acts as a moisture and oxygen-permeable support and protects the lower layer from the outer world. A number of drug delivery systems use polysiloxanes because of the flexibility and porous nature of the material. 

VD Nadkami, T Toida, CL Van Gorp, TL Schubert, JM Weiler, KP Hanse, EEO Caldwell, RJ Linhardt. Preparation and biological activity of N-sulfated chondroitin sulfate derivatives. Carbohydr Res 290 87—96, 1996. 

Enghild JJ, Thogersen IB, Cheng F, Fransson L, Roepstorff P, Rahbek-Nielsen H. Organization of the inter-a-inhibitor heavy chains on the chondroitin sulfate originating from SerlO of bikunin Posttranslational modification of Ial derived bikunin. Biochemistry 1999 38 11804-11813. 

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