| Project/Area Number |
04807162
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
Biological pharmacy
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| Research Institution | Kobe Women's College of Pharmacy |
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Principal Investigator |
SUGAHARA Kazuyuki Kobe Women's Coll.of Pharmacy, Dept.of Physiol.Chem., Professor, 薬学部, 教授 (60154449)
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| Co-Investigator(Kenkyū-buntansha) |
YAMADA Shuhei Kobe Women's Coll.of Pharmacy, Dept.of Physiol.Chem., Instructor, 薬学部, 助手 (70240017)
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| Project Period (FY) |
1992 – 1993
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| Project Status |
Completed (Fiscal Year 1993)
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| Budget Amount *help |
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1993: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 1992: ¥1,000,000 (Direct Cost: ¥1,000,000)
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| Keywords | Heparin / Chondroitin sulfate / Glycosaminoglycans / Galactose / Sulfation / ヘパラン硫酸 / デルマタン硫酸 / プロテオグリカン / グリコサミノグリカン |
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| Research Abstract |
It has become evident that the sulfated glycosaminoglycans exert various biological activities. However, their structure and biosynthetic mechanisms are not fully understood. In this study we carried out structural studies on the carbohydrate-protein linkage region of various sulfated glycosaminoglycans including chondroitin 6-sulfate ad heparin. Although the former is galactosaminoglycans and the latter is glucosaminoglycans, they share the common tetrasaccharide core structure in the carbohydrate-protein linkage region.
We discovered hitherto unreported 4-0-sulfated and 6-0-sulfated galactose-containing structures in the carbohydrate-protein linkage region of chondroitin 6-sulfate prepared from shark cartilage. These strucures were Galbeta1-3Gal(6-0-sulfate)beta1-4Xyl, Gal(6-0-sulfate)beta1-3Gal(6-0-sulfate)beta1-4Xyl and Gal(4-0-sulfate)beta1-3Gal(6-0-sulfate)beta1-4Xyl. In contrast, these structures were not detected in the corresponding region of heparin prepared from porcine intes
… More
tine. Thus, this study has clarified that there are structural differences in the carbohydrate-protein linkage region of chondroitin sulfate and heparin. Based upon these results, we propose a working hypothesis that the sulfation of the galactose residues in the linkage region may be involved in the biosynthetic sorting mechanisms of chondroitin sulfate and heparin. It is possible that tha GalNAc-transferase which transfers the first GalNAc residue to the linkage tetrasaccharide, GlcAbeta1-3Galbeta1-3Galbeta1-4Xyl, recognaizes the sulfated galactose structures while the GlcNAc-transferase which transfers the first GlcNAc residue to the linkage tetrasaccharide is inhibited by these modified structures. This study also revealed that there are a number of subclasses in the chondroitin sulfate chains based upon the structural differences in the carbohydrate protein linkage region. In the future study we plan to investigate the structural relationship between the linkage region and the repeat region where biologically active domain structures are located. Less
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