摘要
水蛭素是高效的凝血酶抑制剂,临床上用于血栓病的防治,效果优于肝素,但水蛭素拥有强大抗凝活性的同时伴随的出血副作用限制了它在临床的推广应用。近年来,通过设计凝血因子FXa识别序列封闭水蛭素,使其体外无活性,而在体内血栓部位被裂解后释放抗凝活性,以及能够寻靶纤维蛋白或血小板的水蛭素融合蛋白,构建了出血风险低的水蛭素抗凝药物,展现了广阔前景。本文将对近年来低出血性水蛭素衍生物的研究状况进行综述。
Hirudin extracted from the secretion of medical leech salivary gland can be used to treat clinically thrombosis as a potent specific inhibitor of thrombin. Hirudin would prolong the bleeding time while inhibit the activity of thrombin, which can induce the bleeding of thrombolysis position. The bleeding risk of hirudin hinders its clinical application. The promising methods have been developed to relieve its bleeding side effect in recent years, such as designing inactNe hirudin derivatives fused with blood coagulation factor Xa （FXa） recognition peptide to close the anticoagulant effect in vitro, but release anticoagulant activity after cleavage by FXa in vivo, or constructing low-bleeding hirudin fusion protein targeted at fibrin or platelet. Through these ways the antithrombotic activity of hirudin derivatives was released in thrombus-targeted way and was limited in the vicinity of the thrombus. The research progress of low- bleeding risk hirudin was summarized in this review.
出处
《生命的化学》
CAS
CSCD
北大核心
2011年第6期924-928,共5页
Chemistry of Life
