hirudin is the most potent and specific thrombin inhibitor and is derived from the medicinal leech . it is reported to inhibit thrombin with an equilibrium dissociation constant value of 2 . 2 × 10 - 14 m . synthetic thrombin inhibitors have been designed based on the hirudin sequence but with a dramatically reduced size . the bulky active site inhibitor segment , hirudin 1 - 48 , has been substituted by small non - substrate type active site inhibitors of thrombin , e . g ., dansyl - arg -. the linker segment has also been modified using a combination of ω - amino acids to reduce the molecular weight but retaining sufficient length to span the two principal binding domains . among the inhibitors designed , dansyl - arg --- 4 - aminobutyric acid )- asp - tyr - glu - pro - ile - pro - glu - glu - ala --- oh showed the highest affinity and displays a competitive - type inhibition . the incorporation of the non - substrate type active site inhibitor segment and the linker of ω - amino acids into the bivalent thrombin inhibitors not only improved in vitro thrombin inhibitory activity to the pm level , overcame proteolytic susceptibility at the level of the &# 34 ; normal &# 34 ; scissile bond and confered high in vivo activity .