Hirudin analogs, methods of manufacture thereof and anticoagulant compositions having these as active ingredients

摘要

Disclosed are hirudin analogs, a method of manufacture thereof, and anticoagulant compositions containing the same. Sequences Asp33-Gly34 or Asp62-Ala63 of naturally-occurring hirudins or their analogs were substituted as disclosed to suppress the formation of succinimide- or beta- forms, thereby yielding hirudin analogs with high stability, high anti-thrombin activity, and therapeutic potential as anticoagulants. Hirudin analogs having Val1-Val2 of naturally-occurring hirudin substituted with Ile1-Ile2 are preferred for their high antithrombiin activity. The invention also provides DNAs encoding the amino acid sequence of hirudin analogs, expression vectors, recombinant microogranisms, and a method of manufacturing hirudin analogs using recombinant microorganisms.