RETEPLASE

Reteplase (recombinant plasminogen activator, r-PA) is a single chain deletion mutant of alteplase that is expressed in Escherichia coli and, therefore, is expressed as an unglycosylated protein (table 1, figs 1 and 2). Reteplase includes 355 amino acids with a total molecular weight of 39 kDa. The molecule consists of cringle 2 and the protease domain of the alteplase molecule. Because of the deletion of the fibronectin finger region, the binding of reteplase to fibrin is significantly reduced in comparison with that of alteplase. Although kringle 2 (known to stimulate protease in the presence of fibrin) is part of the reteplase molecule, reteplase is stimulated in the presence of fibrin to a lower extent than alteplase, suggesting that the fibronectin finger is involved in the stimulation of the protease as well. Reteplase, in comparison with alteplase, is characterised by reduced fibrin selectivity. In the abscence of fibrin, reteplase and alteplase do not differ with respect to their activity as plasminogen activators, nor do they differ with respect to their inhibition by the plasminogen activator inhibitor type 1 (PAI-1).

The elimination of reteplase from the circulating plasma predominantly occurs in the liver. Because of the deletion of the fibronectin finger region, the epidermal growth factor domain and kringle 1, as …