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Structural and thermodynamic studies of G-quadruplexes with unique structural motifs and their recognition by small molecules

  • This dissertation explores and tries to unravel the fundamental basis of G-quadruplex end-folding as well as G-quadruplex interactions with small molecules by thermodynamic and structural approaches. Selective targeting of G-quadruplexes with ligands remains elusive, either because the ligand has considerable binding affinity for other DNA structures or because it fails to discriminate between different G-quadruplex topologies. Unique structural motifs on the G-quadruplex may enhance or inhibit ligand binding to the G-quadruplex. For such aspects, it is necessary to understand the effect of G-quadruplex motifs or elements on the end-folding in order to better tune certain G-quadruplex topologies as model systems. Importantly for targeting G-quadruplex with ligands, motifs called Quadruplex-duplex (QD) junctions and interfaces are shown to be a binding hotspot for various G-quadruplex ligands containing an intercalator motif. Binding affinity and selectivity of the ligands are discussed with the support of the NMR structures.

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Metadaten
Author: Lie, Yoanes Maria Vianney
URN:urn:nbn:de:gbv:9-opus-88035
Title Additional (English):Strukturelle und thermodynamische Untersuchungen von G-Quadruplexen mit besonderen Strukturmotiven und ihre Erkennung durch kleine Moleküle
Referee:Prof. Dr. Klaus Weisz, Prof. Carlos González, Assoc. Prof., Ph.D. Lukas Trantirek
Advisor:Prof. Dr. Klaus Weisz
Document Type:Doctoral Thesis
Language:English
Year of Completion:2023
Date of first Publication:2023/09/18
Granting Institution:Universität Greifswald, Mathematisch-Naturwissenschaftliche Fakultät
Date of final exam:2023/09/06
Release Date:2023/09/18
GND Keyword:G4QD
Page Number:343
Faculties:Mathematisch-Naturwissenschaftliche Fakultät / Institut für Biochemie
DDC class:500 Naturwissenschaften und Mathematik / 540 Chemie