摘要 |
Disclosed are: a method for enhancing the enzymatic activity of ADAMTS-13 and/or a method for reducing the reactivity of ADAMTS-13 with an anti-ADAMTS-13 neutralizing antibody; and an ADAMTS-13 mutant which is produced by the method. The method is characterized by substituting at least one charged amino acid residue located in a disintegrin-like domain, a cysteine-rich domain or a spacer domain of ADAMTS-13 other than the following amino acid residues by another amino acid residue: an arginine residue at position-326, an aspartic acid residue at position-330, an aspartic acid residue at position-343 and an arginine residue at position-349 in the disintegrin-like domain; an aspartic acid residue at position-480, an arginine residue at position-488, an arginine residue at position-498, an arginine residue at position-507, an aspartic acid residue at position-533 and an aspartic acid residue at position-543 in the cysteine-rich domain; and a glutamic acid residue at position-641 and an arginine residue at position-660 in the spacer domain. Further disclosed is a therapeutic agent for a thrombotic disease, which comprises the ADAMTS-13 mutant produced by the method as an active ingredient. |