Home > Science & Mathematics > Chemistry > Strukturelle Charakterisierung Von Platin-1,3-Gg Intrastrand Crosslinks in Kurzen Oligonukleotiden Mittels Nmr-Spektroskopie Und Untersuchungen Zur Mismatch-Erkennung in Doppelstrangiger DNA Durch Sterisch Gehinderte Platinkomplexe
Strukturelle Charakterisierung Von Platin-1,3-Gg Intrastrand Crosslinks in Kurzen Oligonukleotiden Mittels Nmr-Spektroskopie Und Untersuchungen Zur Mismatch-Erkennung in Doppelstrangiger DNA Durch Sterisch Gehinderte Platinkomplexe

Strukturelle Charakterisierung Von Platin-1,3-Gg Intrastrand Crosslinks in Kurzen Oligonukleotiden Mittels Nmr-Spektroskopie Und Untersuchungen Zur Mismatch-Erkennung in Doppelstrangiger DNA Durch Sterisch Gehinderte Platinkomplexe

          
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About the Book

Dissertation auf dem Gebiet der Bioanorganischen Chemie Seit 20 Jahren wird die einfache Platin-Komplexverbindung cis-[(NH3)2PtCl2], Cisplatin, erfolgreich zur Behandlung verschiedener Tumorarten eingesetzt, wobei die DNA der Krebszellen der Angriffsort des Medikaments ist. Es werden dabei vor allem sogenannte 1,2-GG- intrastrand crosslinks gebildet. Das heisst, das Platin bindet sich kovalent an zwei benachbarte Guaninbasen desselben DNA-Strangs. Im Gegensatz dazu ist das geometrische Isomer trans-[(NH3)2PtCl2], Transplatin, therapeutisch inaktiv. Bei der Reaktion von Transplatin mit DNA werden vorwiegend 1,3-GG- intrastrand crosslinks gebildet. Diese wiederum sind unter physiologischen Bedingungen nicht stabil, sondern unterliegen interessanten Umlagerungsreaktionen, die moglicherweise der Schlussel zum Verstandnis der unterschiedlichen Aktivitaten von cis- und trans-[(NH3)2PtCl2] sind. Im ersten Teil der vorliegenden Arbeit wird die Synthese und Charakterisierung der beiden Transplatin-1,3-intrastrand Crosslinks d(CG*TG*) und d(TCG*TG*) beschrieben. (Der hochgestellte Stern markiert die Platinierungsstelle in den Oligonukleotiden.) Mit Hilfe ein- und zweidimensionaler NMR-Spektroskopie wurden Informationen uber die Konformation des Zucker-Phosphat Ruckgrates der Platin-DNA-Addukte gewonnen. Die Umlagerungsreaktion zu den korrespondierenden 1,4-intrastrand-Crosslinks wird mittels NMR-Spektroskopie verfolgt. Im zweiten Teil der Arbeit wird die Reaktivitat der sterisch anspruchsvollen monofunk-tionellen Komplexe cis-[(NH3)2Pt(1-MeC)(OH2)]2+ und cis-[(NH3)Pt(1-MeC)2(OH2)]2+ (1-MeC = 1-Methylcytosin) gegenuber exponierten Guaninbasen in doppelstrangiger DNA mit Hilfe von Gelelektrophorese untersucht. Insbesondere wird die Fahigkeit dieser Komplexe zur Erkennung verschiedener single base mismatches gepruft. In der Reihe von Platinkomplexen cis-[(NH3)2(1-MeC)Pt(OH2)]2+, cis-[( NH3)(1-MeC)2Pt(OH2)]2+ und [(1-MeC)3Pt(OH2)]2+ wird cis-[(NH3)(1-MeC)2Pt(OH2)]2+ als derjenige mit der optimalen Reaktionsgeschwindigkeit bei gleichzeitig erhaltener Selektivitat fur exponierte Guaninbasen identifiziert.


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Product Details
  • ISBN-13: 9783897226425
  • Publisher: Logos Verlag Berlin
  • Publisher Imprint: Logos Verlag Berlin
  • Height: 210 mm
  • No of Pages: 120
  • Series Title: German
  • Weight: 700 gr
  • ISBN-10: 3897226421
  • Publisher Date: 30 Apr 2001
  • Binding: Paperback
  • Language: German
  • Returnable: N
  • Spine Width: 0 mm
  • Width: 145 mm

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Strukturelle Charakterisierung Von Platin-1,3-Gg Intrastrand Crosslinks in Kurzen Oligonukleotiden Mittels Nmr-Spektroskopie Und Untersuchungen Zur Mismatch-Erkennung in Doppelstrangiger DNA Durch Sterisch Gehinderte Platinkomplexe
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Strukturelle Charakterisierung Von Platin-1,3-Gg Intrastrand Crosslinks in Kurzen Oligonukleotiden Mittels Nmr-Spektroskopie Und Untersuchungen Zur Mismatch-Erkennung in Doppelstrangiger DNA Durch Sterisch Gehinderte Platinkomplexe
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Strukturelle Charakterisierung Von Platin-1,3-Gg Intrastrand Crosslinks in Kurzen Oligonukleotiden Mittels Nmr-Spektroskopie Und Untersuchungen Zur Mismatch-Erkennung in Doppelstrangiger DNA Durch Sterisch Gehinderte Platinkomplexe

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