| 摘要 |
The invention provides staphylokinase derivatives showing a reduced immunogenicity as compared to wild-type staphylokinase, in particular staphylokinase derivatives having essentially the amino acid sequence of wild-type staphylokinase or modified versions thereof, but wherein at least one immunodominant epitope is eliminated without destroying the biological activity of the derivatives. The invention further relates to a method for producing the staphylokinase derivatives comprising the steps of preparing a DNA fragment comprising at least the part of the coding sequence of staphylokinase that provides for its biological activity; performing in vitro site-directed mutagenesis on the DNA fragment to replace one or more codons for wild-type amino acids by a codon for another amino acid; cloning the mutated DNA fragment in a suitable vector; transforming or transfecting a suitable host cell with the vector; and culturing the host cell under conditions suitable for expressing the DNA fragment, and pharmaceutical compositions comprising at least one of the derivatives for treating arterial thrombosis. |
