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Science 4 May 1990:
Vol. 248. no. 4955, pp. 593 - 596
DOI: 10.1126/science.2333510
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Articles

Science, Vol 248, Issue 4955, 593-596
Copyright © 1990 by American Association for the Advancement of Science

articles

Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa

L Waxman, DE Smith, KE Arcuri, and GP Vlasuk

Biological Chemistry Department, Merck Sharp & Dohme Research Laboratories, West Point, PA 19486.

A low molecular weight serine protease inhibitor (TAP) was purified from extracts of the soft tick, Ornithodoros moubata. The peptide is a slow, tight-binding inhibitor, specific for factor Xa (Ki = 0.588 +/- 0.054 nM). The inhibitor also acts as an anticoagulant in several human plasma clotting assays in vitro. Its amino acid sequence (60 residues) has limited homology to the Kunitz-type inhibitors. However, unlike other inhibitors of this class, TAP inhibits only factor Xa. It had no effect at a 300-fold molar excess on factor VIIa, kallikrein, trypsin, chymotrypsin, thrombin, urokinase, plasmin, tissue plasminogen activator, elastase, or Staphylococcus aureus V8 protease. TAP's specificity and size suggest that it may have therapeutic value as an anticoagulant.


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