title: Properties of molecular variants of tissue-type plasminogen activator.
abstract: Tissue-type plasminogen activator (t-PA), an important component of the fibrinolytic system, is now available as a biotechnologically manufactured recombinant protein for therapeutic use. It has proved highly effective in the clinical therapy of acute thromboembolic diseases such as myocardial infarction and pulmonary embolism. t-PA activates plasminogen to plasmin, which subsequently dissolves the fibrin network of a blood clot. This activation by t-PA occurs selectively on the clot surface, with negligible systemic side effects. The half-life of t-PA in vivo is in the order of minutes due to rapid hepatic elimination. t-PA is a glycoprotein with serine protease activity and consists of a polypeptide chain with 527 amino acids. Recently, intensive research efforts have been devoted to modification of the molecular structure of t-PA, with the objective of further increasing fibrin specificity and catalytic activity, or reducing the rate of elimination. As a result, considerable insights into structure-function relationships within the t-PA molecule have been gained, but as yet no clinically utilizable variant has been constructed which is in all respects superior to naturally occurring t-PA.
authors.affiliation: Department of Research and Development, Dr. Karl Thomae GmbH, Biberach an der Riss, Fed. Rep. of Germany.
authors.forename: J
authors.initials: J
authors.lastname: Krause
authors.forename: P
authors.initials: P
authors.lastname: Tanswell
mesh_terms: D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D006801:Humans; D007536:Isomerism; D010959:Tissue Plasminogen Activator / Q000032:analysis* / Q000502:physiology / Q000627:therapeutic use
chemical_list: D010959:Tissue Plasminogen Activator