Japan Energy Corporation

Fuji Yakuhin Kogyo Kabushiki Kaisha

Nippon Mining Co., Ltd.

Akiko Sukesada

Satoru Misawa

Tadanori Morikawa

Kyoichi Kobashi

Masaharu Nakano

Eriko Nukui

Koichi Wada

Ryo Muramatsu

Hitoshi Matsuda

Disclosed are hirudin analogs, a method of manufacture thereof, and anticoagulant compositions containing the same. Sequences Asp.sup.33 -Gly.sup.34 or Asp.sup.62 -Ala.sup.63 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 Val.sup.1 -Val.sup.2 of naturally-occurring hirudin substituted with Ile.sup.1 -Ile.sup.2 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.

Hirudin analogs, methods of manufacture thereof and anticoagulant

The present invention relates to hirudin variants having high anti-thrombin and anti-platelet activity, methods for producing them, and anti-coagulants having said variants as active ingredients. Hirudin variants shown in formula (I) having tyrosine residues or having their hydroxyl group sulfated. Methods for producing hirudin variants by sulfating hydroxyl group of said tyrosine residues, and anti-coagulants having hirudin variants shown in formula (I) as active ingredients.

Anticoagulant hirudin variants and methods for their production

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Toda, Japan

Akiko Sukesada