Alteplase protein

FFeart disease, particularly clogged blood vessels, is also treated with recombinant products. Alteplase (Activase ), a human recombinant protein that breaks down fibrin, is used immediately after a stroke or heart attack to break down platelet-trapping clots in small blood vessels of the heart or brain and thus improve the patient s chances for recovery. Purified enzymes from bacteria are used for the same purposes. Abciximab (ReoPro ), a monoclonal antibody to... 

Proteins, recombinant DNA ORIGIN alteplase anistreplase tenecteplase... 

The advent of recombinant DNA technology has allowed the isolation of genes and expression of proteins that are found in biologic tissues in exceedingly small quantities. This has permitted large-scale production of enzymes such as tissue plasminogen activator (i.e., tPA, alteplase) that cannot be extracted from tissues in quantities required for therapeutic use. Table 9.2... 

Protein manipulation for enzyme proteins can serve as a good example of several possible manipulations. Alteplase is a thrombolysis enzyme protein used to prevent death in acute myocardial infarction. The protein has 527 amino acids, 5 disulfide bridges, glycosylation at several amino acids, and 5 peptide domains. Truncation of most domains leaving intact the protease domain resulted in a new biological, reteplase (Retevase), with quite similar thrombolytic activity. Another set of... 

The first protein enzyme developed in the late 1980s was alteplase (t-PA), a thrombolytic agent used to minimize complications owing to blood coagulation... 

Alteplase, reteplase Recombinant human protein 2-10 min Active tissue plasminogen activator, (t-PA) converts plasminogen to plasmin intravenous infusion (alteplase) or bolus doses (reteplase) required. Most expensive. Reteplase is somewhat longer-acting than alteplase... 

The potential utility of enzymes as pharmaceuticals was noted many decades ago, and since then, nearly two dozen enzymes have been developed to treat a variety of diseases. Almost all enzyme therapies developed to date are used to deal with a loss of function defect (a mutation that diminishes activity, a low level of production, a deletion). Hence, most enzyme drugs are used as enzyme replacement therapies (ERT) for relatively rare, inborn errors of metabolism (lEMs). As a result, many enzyme therapeutics fall under the FDA s Orphan Drug Designation. However, a few enzyme therapies can also be used to treat much more common conditions such as cancer, heart attacks, and stroke. In the United States, the first enzyme to receive FDA approval was a tissue plasminogen activator called alteplase. This protein, which is now commonly used to treat strokes, was introduced in 1987 as Activase. Since then at least 16 other enzyme drugs have been introduced into the marketplace. Some of these are described in more detail below and in Table 6.1-3. 

Nugyen TH, Carole W. Stability characterization and formulation development of Alteplase, a recombined tissue plasminogen activator. In Wang YJ, Pearlman R, eds. Stability and Characterization of Protein and Peptide Drugs Case Histories. New York Plenum Press, 1993 91-133. 

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