MATERIALS AND METHODS RELATING TO ENDOTHELIAL CELL GROWTH INHIBITORS

摘要

Proteolytic enzymes are involved in generation of a number of endogenous angiogenesis inhibitors and it has been shown that urokinase-activated plasmin can process plasminogen to release an angiogenesis inhibitor, K1-5 (protease-activated kringles 1-5). However, this proteolytic protein (proteolytic K1-5) cannot be secreted (exported) from cells and thus is limited in its application as a therapeutic. The present inventors have now engineered a recombinant protein derived from plasminogen which is folded correctly such that it can be secreted from cells in which it is expressed. The inventors surprisingly found that in order to fold correctly such that it can be secreted, the recombinant protein must comprise a secretory signal peptide and a pre-activation peptide derived from plasminogen.