THROMBOLYTIC AGENTS DERIVED FROM STREPTOKINASE

摘要

Structural information about the streptokinase-micro plasminogen complex has been used to identify the part of the streptokinase structure not involved i n plasminogen complexation or activation. These nonessential portions can be modified to reduce antigenicity, for example, by changing the nonessential portions of streptokinose to more human-like polypeptide portions ("humanization of streptokinase"). One way this can be done is to compare th e nonessential portion to a structural database of human proteins to find similar structures. Then the streptokinase nonessential structural part is replaced with the human structural part such as by genetic engineering of a mutant encoding the individual streptokinases, which is then expressed in a bacterial host such as E. coli. Alternatively, the nonessential portions can be removed or truncated to simplify streptokinase to a smaller molecule whic h retains plasminogen activation activity. Such smaller proteins should have reduced antigenicity and be cheaper and easier to produce. The modified streptokinases are useful in treating clotting disorders.