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Strukturelle Untersuchungen zur anaplastischen Lymphomkinase

Strukturelle Untersuchungen zur anaplastischen Lymphomkinase

Carla Donadoni

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Editorial:
KS OmniScriptum Publishing
Año de edición:
2025
Materia
Biologia, ciencias de la vida
ISBN:
9786200687029
73,72 €
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Die ALK-Tyrosinkinase wird als NMP/ALK-Fusionsprotein in etwa 60 % der Fälle von anaplastischem großzelligem Lymphom (ALCL) und in anderen Krebsarten wie nicht-kleinzelligem Lungenkrebs (NSCLC) und Neuroblastom exprimiert. Die konstitutive Aktivierung der ALK-Kinasedomäne ist für die maligne Transformation verantwortlich. Die strukturelle Charakterisierung der ALK-Kinasedomäne und Informationen über Wechselwirkungen zwischen Medikamenten und Proteinen könnten für die rationale Entwicklung neuer spezifischer Medikamente zur Behandlung von ALK+ ALCL und anderen ALK+ Tumoren sehr nützlich sein. Diese Arbeit konzentrierte sich auf die Herstellung und Reinigung verschiedener Formen der ALK-Kinasedomäne, um gute Kandidaten für ALK-Strukturuntersuchungen mittels Röntgenkristallographie und STD-NMR zu erhalten. Die beste rekombinante Proteinform wurde verwendet, um potenzielle ALK-Inhibitoren zu screenen und die Wechselwirkung zwischen der ALK-Kinasedomäne und einem neuen Kinase-Inhibitor nachzuweisen. Die Ergebnisse dieser Arbeit könnten den Weg für die Entwicklung neuer spezifischer Medikamente zur Behandlung von ALK+-Erkrankungen ebnen. Diese Arbeit könnte ein methodisches Modell für die Herstellung und Reinigung rekombinanter Proteine und für weitere Studien zur Wechselwirkung zwischen Medikamenten und Proteinen liefern.

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