Ding Fei-Xiang, Yan Hong-Li, Lu Yi-Ming, Xue Geng, Mei Qian, Huang Jing-Jing, Zhao Zhuan-You, Wang Yu-Zhao, Sun Shu-Han
Department of Medical Genetics, The Second Military Medical University, Xiangyin Road 800, Shanghai 200433, China.
J Biotechnol. 2006 Nov 10;126(3):394-405. doi: 10.1016/j.jbiotec.2006.04.037. Epub 2006 May 7.
The development of thrombolytic agent could provide invaluable progress for antithrombotic therapy. In this paper, we reported the cloning, purification and biochemical characterization of AnxB1ScuPAFap, a thrombus-ditargeting chimera composed of annexin B1, low molecular single-chain urokinase (ScuPA-32K) and fibrin-adherent peptide (dodecapeptide, Fap). In vitro test showed that, the chimera was a thrombolytic agent with anticoagulant activity and thrombus-ditargeting with the activated-platelet membrane binding and fibrin clot binding activity. Compared to urokinase, the chimera had less reperfusion time, higher reperfusion ratio, and less bleeding effects on coronary thrombolysis by clot lysis assay in dogs. Thus, the chimera appeared to be suitable for thrombolytic therapy of thrombus diseases.
溶栓剂的研发可为抗血栓治疗带来宝贵进展。在本文中，我们报道了AnxB1ScuPAFap的克隆、纯化及生化特性，AnxB1ScuPAFap是一种由膜联蛋白B1、低分子单链尿激酶（ScuPA-32K）和纤维蛋白黏附肽（十二肽，Fap）组成的血栓双靶点嵌合体。体外试验表明，该嵌合体是一种具有抗凝活性的溶栓剂，对活化血小板膜和纤维蛋白凝块具有双靶点结合活性。与尿激酶相比，通过犬类冠状动脉血栓溶解试验的凝块溶解分析，该嵌合体的再灌注时间更短、再灌注率更高，且溶栓后出血效应更小。因此，该嵌合体似乎适用于血栓性疾病的溶栓治疗。
