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Hamostaseologie 1989; 09(03): 114-121
DOI: 10.1055/s-0038-1655260
DOI: 10.1055/s-0038-1655260
Originalarbeiten
Die molekularbiologischen Eigenschaften des Gewebetyp-Plasminogenaktivators und seiner Varianten
Further Information
Publication History
Publication Date:
25 June 2018 (online)
Zusammenfassung
Der Gewebetyp-Plasminogenaktivator (t-PA) ist ein Schlüsselenzym der physiologischen Fibrinolyse und steht heute auch als rekombinantes Protein für therapeutische Zwecke zur Verfügung. Biotechnisch hergestelltes t-PA (Actilyse®) verzeichnet bereits beachtliche klinische Erfolge bei der Behandlung von thromboembolischen Erkrankungen, insbesondere dem akuten Herzinfarkt. t-PA aktiviert Plasminogen zu Plasmin, welches das Fibringerüst eines Thrombus auflösen kann. Diese Aktivierung erfolgt selektiv auf der Thrombusoberfläche und verursacht nur geringe systemische Nebenwirkungen. Die Halbwertszeit von t-PA in vivo ist aufgrund einer raschen hepatischen Elimination sehr kurz (3-5 min).
t-PA ist ein Glykoprotein mit Serinproteaseaktivität, dessen Polypeptidkette aus 527 Aminosäuren besteht und über insgesamt 17 Disulfidbrükken verknüpft ist. Mit dem Ziel, Fibrinspezifität und katalytische Aktivität zu erhöhen oder die Eliminationsrate zu verringern, haben zahlreiche Forschergruppen in jüngster Zeit Modifikationen der molekularen Struktur von t-PA durchgeführt. Durch diese Arbeiten wurden zwar interessante Beziehungen zwischen Struktur und Funktion des t-PA-Moleküls aufgedeckt, jedoch konnte bisher keine klinisch relevante Variante konstruiert werden, die dem natürlich vorkommenden Protein in der Summe seiner Eigenschaften überlegen ist.
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