Structure of recombinant habutobin protein and relation withexpression of antithrombotic activity

重组哈布图宾蛋白的结构及其与抗血栓活性表达的关系

• 批准号: 21390060
• 负责人: KOSUGI Tadayoshi
• 金额: $ 10.48万
• 依托单位: University of the Ryukyus
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2011
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21390060/
• 关键词: 抗血栓活性; 抗血小板剤; 血小板; ハブトビン; 組換え蛋白体; 蛇毒; 組換え蛋白質; 構造機能連関; 抗血栓剤; 抗血小板; 組換え体蛋白質

Habutobin expresses antithrombotic action by defibrinogenation, acceleration of fibrinolysis, and inhibition of platelet aggregation. Structural determination of the site responsible for the action of habutobin underlies the development of antithrombotic agents with multiple pharmacological actions. Habutobin cDNA was cloned and 4 fragments of recombinant habutobin (habu-mut 1, 2, 3 and 4) each with different target sites were constructed. It was found that habu-mut2 suppressed collagen-induced platelet aggregation by approximately 10%, and habu-mut3 suppressed it by approximately 20-30%. Novel antithrombotic agents can be developed by structural analysis.

哈布托宾通过去纤维蛋白原、加速纤维蛋白溶解和抑制血小板聚集来发挥抗血栓作用。哈布图宾作用位点的结构确定是开发具有多种药理作用的抗血栓药物的基础。克隆了哈布托宾 cDNA，并构建了 4 个重组哈布托宾片段（habu-mut 1、2、3 和 4），每个片段都有不同的靶位点。研究发现，habu-mut2 可抑制胶原诱导的血小板聚集约 10%，habu-mut3 可抑制约 20-30%。通过结构分析可以开发新型抗血栓药物。

项目成果

RNAi targeting embryonic myosin heavy chain isoform inhibited bound thrombin-induced migration of vascular smooth muscle cells

靶向胚胎肌球蛋白重链亚型的 RNAi 抑制结合凝血酶诱导的血管平滑肌细胞迁移

• 发表时间: 2009
• 期刊: J Vasc Res
• 影响因子: 1.7
• 作者: Sunagawa M;Shimada S;Nakamura M;Kosugi T
• 通讯作者: Kosugi T

組換えハブトビンは、家兎洗浄血小板コラーゲン凝集を抑制する

重组哈布宾抑制兔洗涤血小板胶原蛋白聚集

• 发表时间: 2012
• 作者: 中村真理子;砂川昌範;小杉忠誠
• 通讯作者: 小杉忠誠

A fragment of recombinant habutobin inhibited collagen-induced platelet aggregation

重组哈布宾片段抑制胶原诱导的血小板聚集

• 发表时间: 2013
• 作者: M. Nakamura;M. Sunagawa;T. Kosugi
• 通讯作者: T. Kosugi

Transition of pathophysiological significance of plasminogen activator inhibitor-From a chief player in antiinflammation, antifibrinolysis to that in the development of insulin resistance

纤溶酶原激活剂抑制剂病理生理意义的转变——从抗炎、抗纤维蛋白溶解的主要作用到胰岛素抵抗的发展

• 发表时间: 2010
• 期刊: Pathophysiology
• 作者: Kosugi T;Nakamura M;Sunagawa M
• 通讯作者: Sunagawa M

Recombinant habutobin exerted fibrin-forming activity on rabbit fibrinogen and inhibited collagen-induced aggregation of rabbit platelet

重组哈布托宾对兔纤维蛋白原发挥纤维蛋白形成活性并抑制胶原诱导的兔血小板聚集

• 发表时间: 2009
• 作者: Sunagawa;M
• 通讯作者: M