Date of Award
Honors Thesis (Open Access)
Colby College. Chemistry Dept.
Shari U. Dunham
As alternative structures to the double helix, G-tetrads are thought to occur in DNA with many repeating deoxyguanosines (dG). These tetrads have one dG on each corner of a plane and can stack into tetraplexes that can be aptamers and may be found in telomeres. G-tetrads are destabilized by incorporation of 6-thiodeoxyguanosine (?sdG). Addition of metal ions that bind sulfur may stabilize these ?sdG-tetrads. We have carried out a survey of metal ion titrations into ?sG. Stable ?sG:MD? complexes were found for Hg2? (2:1), Cd2? (4:1), Ag2? (0.7:1) and Pt2? (thought to be 2:1). UV/Visible spectrophotometry indicates that G-tetrads containing two ?sG bases can be stabilized by coordination of Hg2?. 1H-NMR and HPLC experiments with Pt2? and ?sG demonstrated complex formation. A technique was developed for isolating the species via HPLC and determining the ratio of ?sG:Pt via UV/Vis and ICPAES. Studies of a thrombin inhibitor DNA aptamer containing two ?sdG bases with UV/Vis indicated formation of a Hg2?-aptamer complex. A thrombin inhibition assay conducted with the Hg2?-aptamer suggested that there was minimal inhibition, indicating the Hg2?-aptamer did not form the expected tetraplex structure. Modifications to the thrombin inhibition experiment to stabilize the Hg2?-aptamer are discussed.
Quadruplex nucleic acids, 6-thioguanosine, DNA, Chemical equilibrium, Metal ions -- Stability
Recommended CitationDrees, Julia, "Metal ion stabilization of G-tetrads containing 6-thioguanosine" (2001). Honors Theses. Paper 74.
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