由于严重的出血副作用，寻找安全有效的靶向性抗血栓药物具有重要的意义。炎症促进高凝状态，血栓又激活多种炎症途径，炎症部位高表达的选择素可作为血栓前状态及血栓形成的标志物。唾液酸路易斯寡糖（SLeX）是选择素的特异性底物，可以作为药物的特异性糖类载体发挥靶向作用。血栓调节蛋白（TM）可作用于多个环节发挥抗凝、纤溶、抗炎等功能。我们推测将重组血栓调节蛋白活性片段（rTM）和SLeX通过点击化学方法定点偶联，构建得到的rTM-PEG-（multi-）SLeX糖蛋白化合物可靶向定位于血栓形成部位，并通过调控NF-κB信号通路起到抗血栓作用。在已获得的rTM-N3及rTM-PEG500-SLeX基础上，本项目拟构建并优化筛选得到性质优良的rTM-PEG-（multi-）SLeX糖蛋白化合物，明确其靶向抗血栓作用及机制，从一个新的视角为血栓性疾病的靶向预防和治疗探索一条可行的研究策略。

The effectiveness of the developed antithrombotic agents so far remains limited by systemic side effects, such as major bleeding complications. It has great significance to find safe and effective targeted agents. Thrombosis and inflammation are biologically inseparable processes. Inflammatory are capable of activating coagulation and inhibiting fibrinolysis, whereas the procoagulant thrombin is capable of stimulating multiple inflammatory pathways. Selectins as adhesion molecules expressed during endothelial activation can be the biomarkers of thrombosis. Sialyl lewis x (SLex) is the specific substrate of selectins. As a specific drug vehicle, we propose SLeX decorated TM through a polyethylene glycol（PEG）triazole structure termed as an inflammatory site-specific antithrombotic agent through the NF-κB signal pathway. Based on the preliminary study, in this project, we will synthetize a series ofrTM-PEG-（multi-）SLeX glycoprotein, test the anticoagulant activity ,site-specific property and mechanism, provide a rational design strategy for generating anticoagulant drugs.