title: Identification of an anticoagulant peptide that inhibits both fXIa and fVIIa/tissue factor from the blood-feeding nematode Ancylostoma caninum.
abstract: 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.
authors.affiliation: Department of Parasitology, Guangdong Medical College, Zhanjiang 524023, China.
authors.forename: Deng
authors.initials: D
authors.lastname: Li
authors.forename: Qingfeng
authors.initials: Q
authors.lastname: He
authors.forename: Tao
authors.initials: T
authors.lastname: Kang
authors.forename: Huan
authors.initials: H
authors.lastname: Yin
authors.forename: Xian
authors.initials: X
authors.lastname: Jin
authors.forename: Hui
authors.initials: H
authors.lastname: Li
authors.forename: Weiqiong
authors.initials: W
authors.lastname: Gan
authors.forename: Chen
authors.initials: C
authors.lastname: Yang
authors.forename: Jingjing
authors.initials: J
authors.lastname: Hu
authors.forename: Yamin
authors.initials: Y
authors.lastname: Wu
authors.forename: Lifei
authors.initials: L
authors.lastname: Peng
mesh_terms: D000595:Amino Acid Sequence; D000722:Ancylostoma / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000925:Anticoagulants / Q000302:isolation & purification / Q000494:pharmacology*; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics; D005167:Factor VII / Q000037:antagonists & inhibitors*; D015945:Factor XIa / Q000037:antagonists & inhibitors*; D006801:Humans; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D010455:Peptides / Q000235:genetics / Q000302:isolation & purification / Q000494:pharmacology*; D011517:Prothrombin Time
chemical_list: D000925:Anticoagulants; D018076:DNA, Complementary; D010455:Peptides; D005167:Factor VII; D015945:Factor XIa