Redesigning t-PA for improved thrombolytic therapy.
Attempts are being made to redesign the structure of tissue-type plasminogen activator (t-PA) in order to increase its plasma half-life, increase its fibrin affinity or decrease its rate of interaction with plasma inhibitors. The principal strategies employed so far have been to construct hybrid enzymes, to mutate the polypeptide sequence of t-PA or to add extra fibrin-binding elements. It has been relatively easy to alter the half-life of t-PA but more difficult to do this with retention of the full specific activity of the molecule; the most promising molecules will have to be evaluated in the clinic before we know whether the redesign of t-PA has been truly successful.
Robinson
J H
JH
SmithKline Beecham Pharmaceuticals, Epsom, Surrey UK.
Browne
M J
MJ
D000596:Amino Acids; D015195:Drug Design; D005337:Fibrin / Q000378:metabolism; D006207:Half-Life; D006801:Humans; D009154:Mutation; D010959:Tissue Plasminogen Activator / Q000235:genetics / Q000493:pharmacokinetics / Q000627:therapeutic use*
D000596:Amino Acids; D005337:Fibrin; D010959:Tissue Plasminogen Activator