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New peptide which inhibits GPIIb/IIIa

Research Project

Project/Area Number 13671055
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Hematology
Research InstitutionFaculty of Medicine, University of Yamanashi

Principal Investigator

OZAKI Yukio  University of Yamanashi, Faculty of Medicine, Professor, 医学部, 教授 (30134539)

Co-Investigator(Kenkyū-buntansha) SATOH Kaneo  University of Yamanashi, Faculty of Medicine, Research Assistant, 医学部, 教務職員 (20242662)
ASAZUMA Naoki  University of Yamanashi, Faculty of Medicine, Research Associate, 医学部, 助手 (60293445)
Project Period (FY) 2001 – 2002
Project Status Completed (Fiscal Year 2002)
Budget Amount *help
¥4,000,000 (Direct Cost: ¥4,000,000)
Fiscal Year 2002: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2001: ¥3,000,000 (Direct Cost: ¥3,000,000)
KeywordsPlatelets / fibrinogen / GPIIb / IIIa / GPR peptide / platelet aggregation / surface plasmon resonance / 血小板疑集 / 凝集阻害 / フィブリノーゲン
Research Abstract

We found that some collagen-derived peptides containing the GPR sequence inhibited not only collagen-induced platelet aggregation but also that induced by other agonists of platelet activation. The GPR-containing peptides are closely related to the structure of fibrinopeptide A-cleaved fibrinogen end, while it does not bind to fibrinogen itself. Several lines of evidence suggest that these peptides interact with GPIIb/IIIa. However, unlike RGD peptides, they do not have partial agonist effects on GPIIb/IIIa. In order to prove that these peptides interact with GPIIb/IIIa, we purified GPIIb/IIIa from intact platelets, using ConA affinity columns and fixed them onto a tip for the measurement of surface plasmon resonance. Fibrinogen in this system bound to GPIIb/IIIa with the expected affinity constant. However, we were able to demonstrate the inhibitory effect of these GPR-containing peptides on the interaction between GPIIb/IIIa and fibrinogen, the binding between GPIIb/IIIa and these GPR-containing peptides. On the other hand, the biotinylated peptide, fixed to the tip in this system, interacted with GPIIb/IIIa albeit to a small extent. The discrepancy implies that GPIIb/IIIa during the purification procedures may have undergone changes, and have properties distinct from native GPIIb/IIIa. In order to address this issue, GPIIb/IIIa was transfected into CHO cells, and the effects of the GPR-containing peptides on fibrinogen binding to GPIIb/IIIa or their direct binding to GPIIb/IIIa was evaluated. However, we were able to demonstrate the interaction between GPIIb/IIIa and the GPR-containing peptides. Thus, in contrast to our original expectation, it is suggested that the GPR-containing peptides do not interact with GPIIb/IIIa.

Report

(3 results)
  • 2002 Annual Research Report   Final Research Report Summary
  • 2001 Annual Research Report
  • Research Products

    (9 results)

All Other

All Publications (9 results)

  • [Publications] Yi Wu: "Role of Fc receptor γ-chain in platelet glycoprotein Ib-mediated signaling"Blood. 97. 3836-3845 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki-Inoue, K: "Rac, a small guanosine trisphoate-binding protein, and p21-activeted kinase are activated during platelet spreading on collagen-coated surfaces"Blood. 98. 3708-3716 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yi, Wu: "Role of Fc receptor γ-chain in platelet glycoprotein Ib-mediated signaling"Blood. 97. 3836-3845 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Suzuki-Inoue, K: "Rac, a small guanosine trisphosphate-binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surface"Blood. 98. 3708-3716 (2001)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2002 Final Research Report Summary
  • [Publications] Yi Wu: "Role of Fe receptor γ-chain in platelet glycoprotein Ib-mediated signaling"Blood. 97. 3836-3845 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki-Inoue, K: "Rac, a small guanosine trisphoate-binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surfaces"Blood. 98. 3708-3716 (2001)

    • Related Report
      2002 Annual Research Report
  • [Publications] Suzuki-Inoue, K., Ozaki, Y., Kainoh, M., Shin, Y., Wu, Y., Yatomi, Y., Ohmori, T., Tanaka, T., Satoh, K., Morata, T.: "Rhodocytin induces platelet aggregation, by interacting with glycoprotein Ia/IIa(GPIa/IIa, integrin alpha2beta1) : involvement of GPIa/IIa-associated Src and protein tyrosine phosphorylation"Journal of Biological Chemistry. 276. 1643-1652 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Osada, M., Ohmori, T., Yatomi, Y., Satoh, K., Hosogaya, S., Ozaki, Y.: "Involvement of Hic-5 in platelet activation : integrin α IIbβ3-dependent tyrosine phosphorylation and association with proline-rich tyrosine kinase 2"Biochemical Journal. 355. 691-697 (2001)

    • Related Report
      2001 Annual Research Report
  • [Publications] Suzuki-Inoue, K., Ozaki, Y., Yatomi, Y., Ohmori, T., Satoh, K.: "Rac, a small GTP-binding protein, and p21-activated kinase are activated during platelet spreading on collagen-coated surfaces : roles of integrin alpha2 beta1"Blood. 98. 3708-3716 (2001)

    • Related Report
      2001 Annual Research Report

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Published: 2001-04-01   Modified: 2016-04-21  

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