Ergebnisse Der Physiologie, Biologischen Chemie Und Experimentellen Pharmakologie: Band 53
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7 Diese Art der Informationsübertra- gung bietet eine Menge von Vorteilen, von denen hier nur drei erwähnt seien: 1. Verwendung eines einheitlichen biosynthetischen Mechanismus und nur weniger Bausteine (Aminosäuren) zur Herstellung einer unübersehbaren An- zahl möglicher Wirkstoffe. 2. Steuerung des Eintrittes der Wir- kung durch Auslösung des (sehr schnell arbeitenden) Synthesemechanismus auf der Stufe der Gene oder aber durch proteolytische Freisetzung des Wirk- stoffes aus einer unwirksamen Speicher- form (z. B. Angiotensinogen, Abb. 8). 3. Aufhebung der Wirkung in kür- zester Zeit mittels gewöhnlicher proteo- lytischer Enzyme. Für die therapeutische Anwendung von Polypeptidwirkstoffen bedingt Punkt 3 parenterale Verabreichung, weil die Stoffe im Magen-Darm-Trakt proteolytisch zerstört bzw. schlecht resorbiert werden. Diesem Nachteil steht aber der nicht zu überschätzende Vorteil gegenüber, da beim Abbau des Wirkstoffes ausschlie lich physiologische Verbindungen (Aminosäuren) entstehen. Somit ist jede Schädigung durch toxische Abbauprodukte, wie dies bei andern Pharmazeutika manchmal der Fall ist, ausgeschlossen. Im folgenden möchte ich als Beispiel hauptsächlich Wirkstoffe besprechen, an deren synthetischer Entwicklung meine Mitarbeiter und ich besonders beteiligt waren. Es sind dies das Gewebshormon Angiotensin und die Hypophysenhor- mone oc-Melanotropin, -Melanotropin und Corticotropin. Die synthetischen Einzelheiten und Probleme sollen dabei nicht besprochen werden [vgl. dazu 8 ROBERT SCHWYZER: Synthetische Polypeptide mit physiologischer Wirkung SCHWYZER 1961 (b)J, sondern der Hauptakzent liegt auf unseren, durch synthetische Abwandlung der Moleküle gewonnenen Einblicken in Struk- tur-Wirkungs-Beziehungen [für Diskussionen weiter Struktur-Wirkungs-Be- xiehungen auf dem Gebiete der Polypeptide vgl. SCHWYZER 1959, 1961 (a), (c), (d), 1963 (a), (b)J.
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