Department of Parasitology, Guangdong Medical College, Zhanjiang 524023, China.
Biochem Biophys Res Commun. 2010 Feb 5;392(2):155-9. doi: 10.1016/j.bbrc.2009.12.177. Epub 2010 Jan 7.
Factor VIIa-tissue factor complex (fVIIa/TF) and factor XIa (fXIa) play important roles in the initiation and amplification of coagulation, respectively. They may be good targets for the development of novel anticoagulants to treat and prevent thromboembolic disease. In this study, we cloned, expressed and identified a novel anticoagulant peptide, AcaNAP10, from the blood-feeding nematode Ancylostoma caninum. AcaNAP10 showed potent anticoagulant activity and doubled the activated partial thromboplastin and prothrombin times at estimated concentrations of 92.9 nM and 28.8 nM, respectively. AcaNAP10 demonstrated distinct mechanisms of action compared with known anticoagulants. It inhibited fXIa and fVIIa/TF with IC(50) values of 25.76+/-1.06 nM and 123.9+/-1.71 nM, respectively. This is the first report on an anticoagulant that can inhibit both fXIa and fVIIa/TF. This anticoagulant peptide may be an alternative molecule for the development of novel anticoagulants.
组织因子 VIIa-组织因子复合物（fVIIa/TF）和因子 XIa（fXIa）分别在凝血的启动和放大中发挥重要作用。它们可能是开发新型抗凝剂以治疗和预防血栓栓塞性疾病的良好靶点。在这项研究中，我们从食血线虫Ancylostoma caninum 中克隆、表达并鉴定了一种新型抗凝肽 AcaNAP10。AcaNAP10 表现出强大的抗凝活性，在估计浓度为 92.9 nM 和 28.8 nM 时，分别使活化部分凝血活酶时间和凝血酶原时间延长一倍。AcaNAP10 的作用机制与已知的抗凝剂明显不同。它对 fXIa 和 fVIIa/TF 的抑制作用的 IC50 值分别为 25.76+/-1.06 nM 和 123.9+/-1.71 nM。这是首例报道能同时抑制 fXIa 和 fVIIa/TF 的抗凝剂。这种抗凝肽可能是开发新型抗凝剂的替代分子。
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