Bivalirudin is a small synthetic 20-amino-acid peptide that is a specific and reversible inhibitor of thrombin (Parry et al., 1994) (Fig. 1). Although it is an analogue of hirudin, its amino acid sequence is considerably shorter. Bivalirudin unites a carboxy-terminal segment of 12 amino acids (dodecapeptide) derived from native hirudin (residues 53-64), plus a sulfated tyrosine at position 63, to an active site-binding tetrapeptide sequence (D-Phe-Pro-Arg-Pro) at its amino terminal (Maraganore et al., 1990; Nawarskas and Anderson, 2001; White and Chew, 2002). Four glycine residues bridge these two segments together. The amino-terminal segment has a high affinity and specificity for binding to the active site of thrombin (Fareed et al., 1999; Sciulli and Mauro, 2002), while the carboxy terminal binds to the fibrinogen recognition site of thrombin at exosite 1 (Thiagarajan and Wu, 1999; Reed and Bell, 2002). One difference between bivalirudin and hirudin is that the binding of bivalirudin to the active site of thrombin is transient, whereas with lepirudin, irreversible thrombin-hirudin complexes are formed (Weitz and Hirsh, 1998; Nawarskas and Anderson, 2001).

Bivalirudin is produced by solid phase peptide synthesis (Maraganore et al., 1990). Its molecular mass is 2180 Da. Bivalirudin has no structural similarity to heparin.

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