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Title: Structural basis for anticancer drug design : g-quadruplex-ligand complexes and aptamers
Authors: Chung, Wan Jun
Keywords: DRNTU::Science
Issue Date: 2014
Abstract: Guanine-rich oligonucleotides have the propensity to fold into four-stranded helical structures known as G-quadruplex (G4). These structures are involved in cellular processes including replication, transcription and translation, with recent studies demonstrating their existence in cells. G4-forming genomic sequences were shown to be viable drug targets, while synthetic G4 aptamers were demonstrated to elicit anticancer activity. Hence, structural insights on G4-ligand complexes and G4 aptamers will be invaluable for G4-based drug design and development. This thesis is focused on two parts: I) structural study of two complexes between G4s and two highly efficient G4- binders, a telomestatin derivative and a bisquinolinium compound, and II) structural characterization of a G4 isolated from an anticancer aptamer, using NMR spectroscopy and X-ray crystallography. Strikingly, this G4 exhibits an unprecedented left-handed twist, which could serve as a unique recognition element.
Fulltext Permission: restricted
Fulltext Availability: With Fulltext
Appears in Collections:SPMS Theses

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