Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 392, Issue 2, Pages 155-159Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2009.12.177
Keywords
Ancylostoma caninum; Inhibitor; Coagulation; Factor XIa; Factor VIIa; Tissue factor
Categories
Funding
- Zhanjiang Science and Technology Bidding Project, Guangdong Province [2007113]
- Department of Health of Guangdong Province [A2008471]
- Guangdong Natural Science Foundation [04011381]
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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 fur the development of novel anticoagulants to treat and prevent thromboembolic disease. In this Study, we cloned, expressed and identified a novel anticoagulant peptide, AcaNAP10, front 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 IC50 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. (C) 2010 Elsevier Inc. All rights reserved
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