ECOTINE DERIVATIVES

摘要

This invention provides a class binding proteins that specifically bind to and modulate (e.g. enhance) the activity of polypeptides having a chymotrypsin fold (e.g. serine proteases). The binding proteins are based on the structure of ecotin. It was discovered that modification of the amino or carboxyl terminus and/or randomization of one or more of loops 50s, 60s, 80s or 100s will provide an ecotin variant library from which can be selected binding molecules (e.g. protease modulators) specific to virtually any serine protease. Depending on the ecotin variant and the target serine protease, the modulator can act as a serine protease inhibitor or as a serine protease activator. Specific agonists (enhancers) of Factor IXa are disclosed.