Von Willebrand factor (vWF)-cleaving protease
View Patent ↗This invention is intended to isolate and identify a vWF-specific cleaving protease. The vWF-specific cleaving protease cleaves a bond between residues Tyr 842 and Met 843 of vWF and comprises a polypeptide chain having Leu-Leu-Val-Ala-Val (SEQ ID NO: 1) as a partial sequence, and more preferably comprises a polypeptide chain having the partial N-terminal amino acid sequence of a mature protein, Ala-Ala-Gly-Gly-Ile-Leu-His-Leu-Glu-Leu-Leu-Val-Ala-Val (SEQ ID NO: 2), and having a molecular weight of 105 to 160 kDa in SDS-PAGE under reducing or non-reducing conditions. Isolation and identification of this vWF-specific cleaving protease have led to the possibility of replacement therapy for patients having diseases resulting from a deficiency of the protease, such as thrombotic thrombocytopenic purpura.
1. The isolated protease encoded by the nucleotide sequence of SEQ ID NO: 15, comprising a polypeptide chain having the amino acid sequence of SEQ ID NO: 3, wherein the protease is capable of cleaving a bond between residues Tyr-842 and Met-843 of von Willebrand factor.
2. A pharmaceutical composition comprising the protease according to claim 1 .
3. The pharmaceutical composition according to claim 2 , wherein the composition treats diseases caused by deterioration in activity of a protease comprising a polypeptide chain having the amino acid sequence Leu-Leu-Val-Ala-Val, wherein the protease is capable of cleaving a bond between residues Tyr-842 and Met-843 of von Willebrand factor.
4. The pharmaceutical composition according to claim 2 , wherein the composition inhibits platelet aggregation caused by the formation of excess von Willebrand factor high-molecular-weight multimers.
5. The pharmaceutical composition according to claim 2 , wherein the composition treats thrombotic thrombocytopenic purpura.
6. The pharmaceutical composition according to claim 2 , further comprising a pharmaceutically acceptable excipient.