重组日本七鳃鳗RGD毒素肽rLj-RGD3结构与抗血栓活性的关系

项目名称： 重组日本七鳃鳗RGD毒素肽rLj-RGD3结构与抗血栓活性的关系

项目编号： No.81202455

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 药物学、药理学

项目作者： 吕莉

作者单位： 大连医科大学

项目金额： 23万元

中文摘要： 重组日本七鳃鳗RGD毒素肽rLj-RGD3为源自于海洋洄游鱼类日本七鳃鳗口腔腺的可溶性蛋白，其一级结构含有3个RGD(Arg-Gly-Asp)模体。本课题前期于七鳃鳗唾液腺cDNA文库中发现其基因，对其进行了基因克隆、表达及重组蛋白的大量制备，并对其抗血栓功能进行了研究。先期研究结果表明，rLj-RGD3可凭借分子中含有的3个RGD模体而具有抗血小板聚集、抗动脉与静脉血栓形成作用，且出血不良反应小。为了研究其3个RGD模体的作用方式及其对抗血栓活性的影响，本课题拟对野生型rLj-RGD3进行RGD模体的缺失突变，并对野生型及各突变体蛋白的抗血栓作用进行研究，以确定其结构与抗血栓活性的关系及作用机制。本项目的立项与完成，将为七鳃鳗蛋白质组学与基因工程海洋药物的新药研究奠定理论基础，具有科学的原创性、重要的理论价值和广阔的应用前景。

中文关键词： rLj-RGD3；抗血栓；RGD 肽；血小板；整合素

英文摘要： RGD toxin peptide, rLj-RGD3, is a novel recombinant protein from the buccal gland of Lampetra japonica (a kind of marine migratory fish), which contains three RGD (Arg-Gly-Asp) motifs in its primary structure. The gene of Lj-RGD3 was found in the buccal gland cDNA library of Lampetra japonica, and which was cloned and expressed. The purified recombinant rLj-RGD3 was prepared and used to study the antithrombotic effects of which. Previous studies have shown that, rLj-RGD3 has the functions of anti-platelet aggregation and anti-thrombosis (venous thrombosis and arterial thrombosis) due to the RGD motifs, but its bleeding side effects was slight. In order to study the role and mechanism of the three RGD motifs in anti-thrombotic activity, RGD motif deletion mutant of wild-type rLj-RGD3 will be performed, and the antithrombotic effects of wild-type rLj-RGD3 and mutations will be studied. The relationship between the anti-thrombotic functions and structure of Lj-RGD3, as well as the mechanism would be clarified if the project proceeds successfully. These results will be valuable to the proteomics and new marine genetic engineering drug studies of Lampetra japonica with scientific originality, important theoretical significance and broad application prospects.

英文关键词： rLj-RGD3；antithrombosis；RGD peptide；platelet；integrin