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Function and Structure Analyses of Anticoagulant and Vasodilator Isolated from the Salivary Glands of Blood Sucking Insects, and Development of Novel Medicine

Function and Structure Analyses of Anticoagulant and Vasodilator Isolated from the Salivary Glands of Blood Sucking Insects, and Development of Novel Medicine
吸血昆虫唾液腺抗凝剂和血管扩张剂的功能和结构分析及新药开发
批准号:
11557022
负责人:
CHINZEI Yasuo
金额:
$8.64万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
1999
资助国家:
日本
项目状态:
已结题
起止时间:
1999 至 2002

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项目成果

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中文摘要
翻译
吸血昆虫的唾液腺含有一些生物活性物质,控制宿主动物的血液凝固和血管,以帮助持续的吸血。本研究以两种吸血昆虫Triatoma infestans(Ti)、Anopheles stephensi(As)和二棘血蜱Haemaphisalis bispinosa(Hb)为材料,通过对这些生物活性分子的结构、活性和作用方式的分析,阐明这些生物活性分子的生物学意义,并尝试开发新的药物材料。我们建立了这些动物唾液腺EST数据库,分别分析了179、120和218个具有新序列的分子。经杆状病毒表达系统表达和活性分析,分别鉴定出5个、3个和3个新的生物活性分子。从按蚊As的唾液腺中分离并鉴定出一种新的杀虫蛋白Hamadarin。我们发现Hamadalin通过将凝血级联的因子XII和高分子量激肽原结合到这些分子与带负电荷表面的结合位点来抑制这些分子,结果抑制凝血级联和bladikinin的产生,从而抑制炎症。Hamadalin有可能成为开发新型抗凝血抗炎药物的先导分子。
英文摘要
The salivary glands of blood sucking insects contain some bio-active substances to control blood coagulation and blood vessel of host animals for assisting a continuous blood feeding. In this study, we searched these bio-active molecules from the glands and analyzed the molecular structure, activity and mode of action to elucidate the biological significance of these molecules, and tried to develop a material for novel medicine.We used two blood sucking insects, Triatoma infestans (Ti) and Anopheles stephensi (As), and the tick, Haemaphisalis bispinosa (Hb) as material animals. We established the data bases of salivary gland EST of these animals, and analyzed 179, 120 and 218 molecules with novel sequences, respectively. We identified 5, 3, and 3 novel bio-active molecules respectively after expression by baculo virus expression system and analysis of activities.'Hamadarin', one of them is isolated and identified from the salivary glands of anopheline mosquito As. We found hamadalin inhibits factor XII of coagulation cascade and high molecular weight kininogen by binding them to the binding sites of these molecules to negative charged surface, and as results inhibits coagulation cascade and generation of bladikinin and therefore inflammation. Hamadalin has a possibility to be a lead molecules developing novel anticoagulant and anti-inflammation drug.
期刊论文(64)
专著(0)
科研奖励(0)
会议论文
Y.Chinzei: "Function of bioactive substances in the salivary glands from blood sucking insects."Med.Entomol.Zool.,. 51:. 1-11 (2000)
Y.Chinzei:“吸血昆虫唾液腺中生物活性物质的功能。”Med.Entomol.Zool.,。
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通讯作者:
S.Iwanaga, M.Okada, H.Isawa, A.Morita, M.Yuda, Y.Chinzei: "Identification and characterization of novel salivary thrombin inhibitors from the ixodidae tick, Haemaphysalis longicornis"Eur. J. Biochem.. (in press). (2003)
S.Iwanaga、M.Okada、H.Isawa、A.Morita、M.Yuda、Y.Chinzei:“来自 ixodidae 蜱、Haemaphysalis longicornis 的新型唾液凝血酶抑制剂的鉴定和表征”Eur。
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通讯作者:
Hubert Woitasek et.al.: "Analysis of the involvement of the 3'-untranslated regions in regulating mRNA stability for vitellogenin,cyanoprotein a and"Insect Biochem.Mol.Biol.. (in press). (2002)
Hubert Woitasek 等人:“分析 3-非翻译区参与调节卵黄蛋白原、氰蛋白 a 和 Insect Biochem.Mol.Biol. mRNA 稳定性”(正在出版)。
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通讯作者:
Yuji Kaneko et al.: "Effects of recombinant nitrophorin-2 nitric oxide comples on vascular smooth muscle"Biosci. Biotech. Biochem.. 63. 1488-1490 (1999)
Yuji Kaneko 等人:“重组硝基蛋白-2 一氧化氮复合物对血管平滑肌的影响”Biosci。
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共 26 条
    Malarial parasite molecules essential for development from sporoziote to merozoite in the liver stage.
    • 批准号:
      21590472
    • 项目类别:
      Grant-in-Aid for Scientific Research (C)
    • 资助金额:
      $2.91万
    • 财政年份:
      2009
    • 负责人:
      CHINZEI Yasuo
    • 依托单位:
    Studies on the Mechanisms of Stage specific Host Infection in Malarial Parasite
    Infecton Mechanisms of Malarail Parasite Sporozoites to the Liver Cells
    • 批准号:
      16017243
    • 项目类别:
      Grant-in-Aid for Scientific Research on Priority Areas
    • 资助金额:
      $9.6万
    • 财政年份:
      2004
    • 负责人:
      CHINZEI Yasuo
    • 依托单位:
    Sage specific host cell infection mechanism of malarial parasite
    • 批准号:
      14207011
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $28.12万
    • 财政年份:
      2002
    • 负责人:
      CHINZEI Yasuo
    • 依托单位:
    海外基金