
Preparation, in vivo properties and proposed clinical use of polyoxyethylene-modified tissue plasminogen activator and streptokinase
Fibrinolytic agents such as tissue plasminogen activator (tPA) and streptokinase (SK) are important drugs for the treatment of thromboembolic disease including myocardial infarction. Both agents show short half-lives and, since it is a bacterial protein, SK suffers from the added disadvantage of antigenicity. Genetically engineered forms of tPA which possess longer half-lives are being evaluated as potential second-generation drugs. There are a number of reservations as to whether these constructs will show significantly improved clinical efficacy. A general approach to the problem of short half life, however, is the coupling of poly(ethylene glycol) (PEG) to proteins. Both PEG-tPA and PEG-SK have been prepared and studied in vitro and in vivo. Not only do these conjugates show greatly prolonged circulatory half-lives, but PEG-SK reacts only poorly with anti-SK antibodies. This review considers the potential usefulness of these modified proteins as drugs. © 1991.
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- Pharmacology & Pharmacy
- 3214 Pharmacology and pharmaceutical sciences
- 1115 Pharmacology and Pharmaceutical Sciences
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Published In
DOI
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- Pharmacology & Pharmacy
- 3214 Pharmacology and pharmaceutical sciences
- 1115 Pharmacology and Pharmaceutical Sciences