Zyklische Hybride – Rigide Modellstrukturen fur neue Theranostika

By (author) Claudine Herlan

Extent: 381 pages

Publisher: Logos Verlag Berlin

Subjects: Earth & Life Sciences

Series: Beiträge zur organischen Synthese

Series volume number: 94

Language: German

Paperback (Published)

(January 2020)

ISBN: 9783832552374

5.75 x 8.31 inches

Price: $81.00

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Synopsis
Contributing Authors

Die hoch variable Strukturklasse der Peptide zeichnet sich durch Vertreter mit grossem Potenzial in biochemischen und medizinischen Forschungsbereichen aus. Das pharmakokinetische Profil der hoch selektiven Verbindungen ist allerdings durch eine schnelle proteolytische Degradation gepragt. Der Einbau peptidomimetischer Elemente, z. B. Peptoid-Monomeren, sowie eine Rigidifizierung ihrer 3D-Struktur kann die Bioverfugbarkeit von Peptiden signifikant erhohen. Das Ergebnis sind Peptidomimetika mit herausragender Affinitat und Spezifitat, deren modularer Aufbau den Einsatz in einem breiten Anwendungsspektrum ermoglicht. Der Naturstoff Apicidin, ein zyklisches Tetrapeptid, das wahrend eines in silico-Screenings als potenzieller Inhibitor des kanonischen Wnt/ textgreek{ss-Catenin-Stoffwechselwegs identifiziert wurde, diente als Leitstruktur einer umfassenden Bibliothek von kongeneren Makrozyklen. Der Einfluss einzelner Bausteine auf den schwierigen Ringschluss der Tetramere, auf deren multikonformationelle raumliche Struktur sowie auf ihre biologische Aktivitat wurde untersucht. Des Weiteren wurde die Performance makrozyklischer Hybride als neue Klasse zellpenetrierender Molekule erforscht. Der Zusammenhang zwischen dem Einbau einzelner Seitenketten und dem Syntheseerfolg sowie der intrazellularen Lokalisation wurde evaluiert. Die Arbeit gibt einen Einblick in Vielfaltigkeit der kaum erforschten Hybridstrukturen, die kunftig sicherlich weitere Vertreter fur diverse Anwendungen hervorbringen werden.

By (author) Claudine Herlan

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