Tick anticoagulant peptide

In addition to the AT-dependent agents discussed above, various direct Xa inhibitors (e.g., tick anticoagulant peptide, antistatin, DX-9065a) are undergoing clinical testing. Unlike fondaparinux, these drugs also inhibit surface-bound Xa within prothrombinase. 

Stereo diagram of the NMR solution structure of the tick anticoagulant peptide. The crucial N-terminus Arg3 is indicated along with the pattern of cysteine bonds. 

Vlasuk GP. Structural and functional characterization of tick anticoagulant peptide (TAP) a potent and selective inhibitor of blood coagulation factor Xa. Thrombosis and Haemostasis 1993 70 212-216. 

Waxman L, Smith DE, Arcuri KE, Vlasuk GP. Tick anticoagulant peptide (TAP) is a novel inhibitor of blood coagulation factor Xa, Science 1990 248 593. 

In contrast to unfractionated heparin, the factor Xa inhibitor tick anticoagulant peptide (TAP) effectively inhibited coronary arterial thrombosis in a canine electrolytic injury model (57). TAP was also effective in inhibition of the procoagulant properties of whole blood clots in vitro however, it was stated that TAP might be not optimal due to its slow binding kinetics (54). Meanwhile, several low molecular weight direct factor Xa inhibitors are in clinical development (Table I), some of them specifically for the treatment and secondary prevention of ACS. DX-9065a, ZK-807834 and otamixaban have been intensively characterized in vitro and in vivo and are in clinical investigations for the treatment of acute arterial thrombosis. 

Wei A, et al. Unexpected binding mode of tick anticoagulant peptide complexed to bovine factor Xa. J. Mol. Biol. 1998 283 147-154. 

Laroche, Y., Storme, V., De Meutter, J., Messens, )., and Lauwereys, M. (1994) High-level secretion and very efficient isotopic labeling of tick anticoagulant peptide (TAP) expressed in the methylotrophic yeast, Pichia pastoris. Biotechnology (N.Y.), 12, 1119—1124. 

---