PMID: 2502992May 1, 1989Paper

Properties of molecular variants of tissue-type plasminogen activator

Arzneimittel-Forschung
J Krause, P Tanswell

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.

Related Concepts

Related Feeds

Blood Clotting Disorders

Thrombophilia includes conditions with increased tendency for excessive blood clotting. Blood clotting occurs when the body has insufficient amounts of specialized proteins that make blood clot and stop bleeding. Here is the latest research on blood clotting disorders.