@phdthesis{Haase2020, author = {Linn Karen Haase}, title = {Sugar-modified guanosine analogs as versatile tools for shaping G-quadruplex architectures}, journal = {Zucker-modifizierte Guanosinanaloga als vielseitige Werkzeuge zum Modellieren von G-Quadruplexstrukturen}, url = {https://nbn-resolving.org/urn:nbn:de:gbv:9-opus-43293}, pages = {175}, year = {2020}, abstract = {G-quadruplexes (G4s) have been in the focus of research in the last decades for their regulatory roles in vivo and for their use in nano- and biotechnology. However, an understanding of the various factors that drive a particular quadruplex fold remains limited, challenging rational therapeutic targeting and design of these tetrahelical structures. In this regard, insights from modified G-quadruplexes may help to deepen our knowledge of G-quadruplex structure. In this dissertation, sugar-modified guanosine analogs are exploited for their altered conformational preferences regarding both glycosidic bond angle and sugar pucker by their incorporation into different syn positions of the G-core of a model G-quadruplex. Induced structural perturbations as characterized by NMR spectroscopy range from a local change in tetrad polarity to a complete refolding into an unusual structure with a V-shaped loop, a unique G4 structural element in the focus of this work. Detailed conformational analysis of the introduced G analogs and high-resolution structures of the modified quadruplexes reveal a complex interplay of glycosidic torsion angle, sugar pucker preferences and local interactions, which may all play a leading role in driving G4 folding.}, language = {en} }