Kristallstrukturanalyse und Entwicklung von Computermodellen zur Beschreibung der Selektivität von Enzymen am Beispiel der Carboanhydrase

Ein Ziel der modernen Wirkstoffforschung ist die Entwicklung von Arzneistoffen, die selektiv mit einem Zielprotein wechselwirken. Dadurch sollen Nebenwirkungen in einem frühen Stadium der Entwicklung minimiert, wenn möglich sogar ausgeschlossen werden. Bei der strukturbasierten Entwicklung von W...

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Bibliographic Details
Main Author: Weber, Alexander
Contributors: Klebe, Gerhard (Prof. Dr.) (Thesis advisor)
Format: Doctoral Thesis
Language:German
Published: Philipps-Universität Marburg 2004
Subjects:
Kri
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Table of Contents: To minimize side effects in the drug design process the development of selective inhibitors is very important. Here selective 3D QSAR were generated that allow the extraction of physicochemical properties that are selective for carbonic anhydrase (CA) isozymes. On the other hand CA isozymes were successfully docked into CA II, compared with the poses in X-ray strcutures and the affinities of these compounds were predicted with the 3D QSAR models. The cross-reactivity of cyclooxygenase (COX)-2 inhibitors (valdecoxib, celecoxib) with CA was confirmed with affinity data and the X-ray structure of celecoxib in complex with CA II.