Characterization of anticoagulant proteins, kallikrein- and factor Xa inhibitors from the Korean leech, Hirudo nipponia = 거머리로부터 혈액응고에 관련된 kallikrein 및 factor Xa 억제제의 특성분석

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I. Plasma kallikrein inhibitor: A new serine proteinase inhibitor of plasma kallikrein was screened and purified from a native Korean leech species, Hirudo nipponia. The inhibitor, named piguamerin, showed potent inhibitions of plasma and tissue kallikreins as well as trypsin. Sequencing analyses by automated Edman degradation revealed 48 amino acid residues with molecular mass of 5090 Da. Piguamerin is similar to antistasin-type inhibitors with the same spacing of ten cysteines, but shows differences from hirustasin, antistasin, and ghilanten at the surrounding residues of arginine27. The purified inhibitor modulated plasma clotting in tests of activated partial thromboplastin time. The new inhibitor was the first plasma kallikrein inhibitory member of the antistasin-type inhibitors specifically found from leeches, and may be related to the regulation of blood sucking process modulating the action of kallikreins in host vessels. II. Coagulation factor Xa inhibitor: A coagulation factor Xa inhibitor was screened and purified from the body extract of the blood-sucking leech H. nipponia. The inhibitor was found to be a polypeptide of 7366 Da named as tenastasin, with extraordinary richness in proline and lysine. It showed a specific inhibitory activity against human coagulation factor Xa with 0.5 nM of Ki value and 1:1 stoichiometric ratio, but no effect on various serine proteinases such as thrombin, trypsin, chymotrypsin, and elastase. It could prolong the clotting of human plasma at nanomolar concentrations with in vitro potency comparable to those of antistasin or tick anticoagulant peptide (TAP). The partially obtained sequence did not display high similarity toward different factor Xa inhibitors as well as proteinase inhibitors. Therefore, tenastasin, as a specific factor Xa inhibitor, might be useful for the application to various thrombotic diseases.
Advisors
Kang, Ke-Won강계원
Description
한국과학기술원 : 생물과학과,
Publisher
한국과학기술원
Issue Date
1998
Identifier
144187/325007 / 000945047
Language
eng
Description

학위논문(박사) - 한국과학기술원 : 생물과학과, 1998.8, [ viii, 87 p. ]

URI
http://hdl.handle.net/10203/27440
Link
http://library.kaist.ac.kr/search/detail/view.do?bibCtrlNo=144187&flag=dissertation
Appears in Collection
BS-Theses_Ph.D.(박사논문)
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