Hemostatic effects of phospholipid vesicles carrying fibrinogen γ chain dodecapeptide in vitro and in vivo

Yosuke Okamura, Ippei Maekawa, Yuji Teramura, Hitomi Maruyama, Makoto Handa, Yasuo Ikeda, Shinji Takeoka*


研究成果: Article査読

52 被引用数 (Scopus)


We studied prototypes of platelet substitutes that bear on their surface a dodecapeptide, HHLG-GAKQAGDV (H12). The peptide is a fibrinogen γ chain carboxy-terminal sequence (γ400-411) and recognizes specifically the active form of glycoprotein (GP) IIb/IIIa on the surface of activated platelets. We conjugated H12 to the end of poly(ethylene glycol) chains on the surface of a phospholipid vesicle with an average diameter of 220 nm to prepare H12-PEG-vesicles. The half-life of the H12-PEG-vesicles was significantly prolonged by PEG modification, and the ability of H12 on the surface of the vesicle to recognize GPIIb/IIIa was maintained even though the surface was modified with PEG chains. The H12-PEG-veiscles enhanced the in vitro thrombus formation of platelets that were adhering to a collagen-immobilized plate, when thrombocytopenia-imitation blood was passed over the plate. Based on the flow cytometric analyses of PAC-1 binding and P-selectin expression, the H12-PEG-vesicles were shown not to cause platelet activation. Furthermore, the H12-PEG-vesicles dose-dependently shortened the tail bleeding time of thrombocytopenic rats. It was confirmed that the H12-PEG-vesicles had a hemostatic effect and may be a suitable candidate for an alternative to human platelet concentrates transfused into thrombocytopenic patients.

ジャーナルBioconjugate Chemistry
出版ステータスPublished - 2005

ASJC Scopus subject areas

  • バイオテクノロジー
  • バイオエンジニアリング
  • 生体医工学
  • 薬理学
  • 薬科学
  • 有機化学


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