Plasminogen activators (PAs) are fibrinolytic therapeutics used to dissolve blood clots (thrombus) that cause ischemic stroke, acute myocardial infarction and pulmonary embolism, which are among the leading causes of morbidity and mortality worldwide. PAs have been available as enzyme therapeutics (commonly known as “clot busters”) for over two decades; however, their uncontrolled activity results in risks for excessive bleeding and intracranial hemorrhages. With the aim of reducing these potentially fatal, off-target side-effects of available PA therapeutics, we have designed two generations of semi-synthetic, intra-sterically regulated plasminogen activators. Biochemical characterization and <i>in vitro</i> whole-blood clot lysis experiments with these programmable and tunable PAs demonstrate that this approach allows for temporal control of fibrinolysis.

Design of a programmable and tunable semi-synthetic "clot buster"

255th National Meeting (2018)

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