Biosynthetic and Immunochemical Investigation of Sulfated Glycosaminoglycans

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The long term objective of this project is to clarify the biosynthetic mechanisms by which different sulfated glycosaminoglycans are synthesized on the so-called common carbohydrate-protein linkage structure, GlcA beta1-3Gal beta1-3Gal beta1-4Xyl beta1-O-Ser. We performed the structural studies of the carbohydrate-protein linkage region of various proteoglycans and the enzymological studies of the regulatory mechanisms of various glycosaminoglycan sulfotransferases and obtained the following results.1. In the previous study we discovered the new structure, Gal(4-O-sulfate)beta1-3Gal beta1-4Xyl, in the carbohydrate-protein linkage region of chondroitin 4-sulfate proteoglycans from Swarm rat chondrosarcoma. In the present study we found this structure also in whale cartilage chondroitin 4-sulfate.2. We discovered another new structure, Gal beta1-3Gal(6-O-sulfate)beta1-4Xyl, in the carbohydrate-protein linkage region of chondroitin 6-sulfate proteoglycans of shark cartilage.3. The above two new structures could not be found in heparin, suggesting that they are specific to chondroitin sulfate.4. We isolated the peptidoglycans bearing both undersulfated heparan sulfate and oversulfated galactosaminoglycans derived from hybrid proteoglycans of Engelbreth-Holm-Swarm mouse tumor. The oversulfated galactosaminoglycans contained the novel GalNAc 4,6-disulfated structure.5. We found that chondroitin (internal GalNAc)6-O-sulfotransferase, heparan sulfate (GlcNH_2)2-N-sulfotransferase, keratan sulfate (Gal)6-O- sulfotransferase activities were inhibited by various sulfated glycosaminoglycans, and that the former enzymes were activated by polyamines and basic peptides including polylysine-containing segment of c-Ki-ras 2 protein.