APROTININ MUTANT HAVING IMPROVED CHARACTERISTICS

摘要

PROBLEM TO BE SOLVED: To obtain the novel subject mutant which has a positive charge in the neutral pH region, contains a specific mutation of amino acid in the binding region, has improved enzyme-inhibitory, immunological and pharmacodynamic properties and is useful for treatment of surgery operation, multiple trauma, inflammation and the like. SOLUTION: This novel aprotinin mutant has a positive charge of +3--3 at pH 7 and contains the amino acid(s) of Arg 15 or of Arg 15-Ala 17 in the binding region and shows improved enzyme-inhibitory, immunological and pharmacodynamic properties and is useful as a medicine for treatment of surgery operation, reduction of blood loss, multiple trauma, shock and inflammation. This aprotinin mutant is obtained by cloning a vector containing the aprotinin gene using a partial gene of aprotinin, inducing the site-specific mutation of the cloned gene by the PCR technique using the mutation-inducing primer and the selection primer and integrating the gene into a vector and expressing the gene in the host cells.