| 摘要 |
PROBLEM TO BE SOLVED: To obtain a new t-PA variant comprising a t-PA variant having resistance against inhibition due to the serine protease inhibitor of t-PA, capable of strengthening thrombolytic action and reducing the dose, and useful for the treatment of cardiac infarction, lung embolism, or the like. SOLUTION: This new t-PA variant has resistance against inhibition due to the serine protease inhibitor of t-PA, has an acidic amino acid or a neutral one instead of a basic amino acid at the 304-th position in t-PA, can strength thrombolytic action and reduce the dose, and is useful for the treatment of cardiac infarction, lung embolism, serious phlebothrombosis, or the like. The t-PA variant is obtained by mutating a plasmid having cDNA encoding the entire length of wild-type t-PA through oligonucleotide-mediated mutagenesis so as to substitute other amino acid for arginine at the 304-th position which is the reaction site for serine protease inhibitor of t-PA and then by subjecting the transformant to expression. |
