Chemical Identity

Property	Value
Chemical Formula	C287H440N80O110S6
Molecular Weight	6964 Da
CAS Number	112432-66-5
Peptide Class	Polypeptide (65 amino acids)
Origin	Hirudo medicinalis (medicinal leech)
Disulfide Bonds	3

Structure

Hirudin is a 65-amino acid polypeptide anticoagulant from the salivary glands of the medicinal leech (Hirudo medicinalis). It has three disulfide bonds in the N-terminal domain and a highly acidic C-terminal tail containing multiple sulfated tyrosine residues. The compact N-terminal core and extended C-terminus create a bivalent binding mode.

Mechanism of Action

Hirudin is the most potent natural thrombin inhibitor. The N-terminal domain binds the catalytic active site of thrombin, while the sulfated C-terminal tail binds exosite I (fibrinogen-binding site). This bivalent binding is essentially irreversible (Kd ~20 fM), providing complete and specific thrombin inhibition.

Clinical Applications

• Recombinant hirudin (desirudin, lepirudin): HIT type II treatment
• DVT prophylaxis: Post-surgical (desirudin)
• Research tool: Thrombin biology studies
• Medicinal leech therapy: Reconstructive surgery (biofilm disruption)

Pharmacokinetics

• Half-life: 60-100 minutes (native), varies by recombinant form
• Metabolism: Kidney (proteolytic degradation)
• Elimination: Renal
• Route: IV, SC (recombinant forms)

Safety and Side Effects

Bleeding (no antidote), antibody formation with repeated use (especially lepirudin), and anaphylaxis (rare). No pharmacological reversal agent exists.

References

• Markwardt, F. (1991). Hirudin and derivatives as anticoagulant agents. Thrombosis and Haemostasis, 66, 141-152.
• Dodt, J., et al. (1984). The complete amino acid sequence of hirudin. Journal of Biological Chemistry, 259, 11157-11160.