| Project/Area Number |
09680606
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Structural biochemistry
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
KATO Hisao National Cardiovascular Center Research Institute, Director of Division of Etiology and Pathogenesis, 病因部, 部長 (80029959)
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| Co-Investigator(Kenkyū-buntansha) |
HARA Saburo Kyoto Institute of Technology, Faculty of Engineering and Design, Professor, 繊維学部, 教授 (00028193)
大蔵 直樹 国立循環器病センター研究所, 病因部, 流動研究員
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| Project Period (FY) |
1997 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,700,000 (Direct Cost: ¥2,700,000)
Fiscal Year 1998: ¥1,200,000 (Direct Cost: ¥1,200,000)
Fiscal Year 1997: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Keywords | protease inhibitor / blood coagulation / thrombosis / arteriosclerosis / heparin / 抗血栓 |
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| Research Abstract |
(1) Degradation of TFPI by thrombin
It has been shown that TFPI exists in plasma as a free-form and liporptoein-associated forms and also as truncated forms which were caused by proteolysis. We investigated the actions of various proteases on recombinant TFPI and found that thrombin inactivated the functions of TFPI by secific cleavage of three peptide bonds of TFPI
(2) Interaction of TFPI with heparin
We analyzed the interaction of TEPI with heparin by using modified heparin in which N-sulafate, 2-0-sulfate or 6-0-sulfate residues were specifically removed.and by using shorter chains of polysaccharide. The results indicate that all sulfate residues are essential for the interaction and that sugar chain with 14 units has almost the same ability to interact with TFPI as heparin. We also investigated the interaction of two heparin binding sites of TFPI with heparin. We found that Arg257 and Arg259 were essential for the interaction with heparin by using synthetic peptides with C-terminal basic part. We isolated recombinant K3 domain by Baculo virus system and examined the interaction with heparin.
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