STAPHYLOKINASE VARIANT CARRYING MUTATIONS IN THE AMINO AND CARBOXY- TERMINAL EXTENSIONS

摘要

The present invention relates to the development of new derivatives of a bacterial plasminogen activator, Staphylokinase (SAK), carrying extension of one or more amino acid residues with single or multiple cysteines at the amino and/or carboxy terminal ends and their conjugation with PEG (Polyethylene Glycol), resulting in new Staphylokinase derivatives that display altered oligomeric state, enhanced thermal and protease stability and extended plasma half-life. The new derivatives of SAK were obtained by integrating additional amino acid sequences with one or more cysteine residues at one or both ends of natural coding sequences of Staphylokinase; their cloning and expression in a suitable bacterial host; purification of Staphylokinase derivatives to homogeneity and their chemical modification by integrating a PEG molecule to create new biologically active Staphylokinases having higher protein stability and improved in vivo plasma half life, that may enhance the clinical potential of Staphylokinase in thrombolytic therapy for the treatment of cardiovascular diseases.