Prevention of G-quadruplex folding by ligand-mediated stabilization of the G-triplex intermediate

Simple item page
dc.contributor.advisorKerwin, Sean M.
dc.contributor.authorBracey, Harrison E.
dc.contributor.committeeMemberDavid, Wendi
dc.contributor.committeeMemberLewis, Karen A.
dc.date.accessioned2021-01-14T14:39:40Z
dc.date.available2021-01-14T14:39:40Z
dc.date.issued2018-12
dc.description.abstractG-quadruplex DNA is an extensively studied non-canonical DNA structure formed in guanine rich areas of the human genome. It is proposed that G-quadruplex structures play a role in telomere assembly, replication, and transcription. Experimental evidence has shown that an intermediate in the G-quadruplex folding pathway may exist as G-triplex DNA. The structure of G-triplex DNA is similar to that of G-quadruplex DNA. However, the G-triplex structure is unique in that it has a major groove. The goals of this project are to characterize different G-triplex structure topologies and to find small molecular weight ligands that can selectively bind to the major groove and stabilize the G-triplex intermediates to prevent G-quadruplex folding. To characterize G-triplex topology and stabilization, CD spectra and CD-derived melting temperatures (Tm) were compared to UV thermal difference spectra (TDS) and UV derived Tm of a collection of model G-triplex forming oligonucleotides. Potential ligands were identified by an in silico screen between truncated thrombin binding aptamer (T1) and 1.2 million compounds using molecular docking software, Autodock Vina, and a database of commercially available ligands, ZINC12. To determine if potential ligands bind to and stabilize TBA13, UV-vis spectroscopy melting assay and a FRET bound Tm assay employing a dual-labeled T1 oligonucleotide was performed.
dc.description.departmentChemistry and Biochemistry
dc.formatText
dc.format.extent76 pages
dc.format.medium1 file (.pdf)
dc.identifier.citationBracey, H. (2018). <i>Prevention of G-quadruplex folding by ligand-mediated stabilization of the G-triplex intermediate</i> (Unpublished thesis). Texas State University, San Marcos, Texas.
dc.identifier.urihttps://hdl.handle.net/10877/13116
dc.language.isoen
dc.subjectDNA
dc.subjectG-quadruplex
dc.subjectG-triplex
dc.subjectDNA damage
dc.subjectThermal difference spectra
dc.subjectFRET
dc.titlePrevention of G-quadruplex folding by ligand-mediated stabilization of the G-triplex intermediate
dc.typeThesis
thesis.degree.departmentChemistry and Biochemistry
thesis.degree.disciplineBiochemistry
thesis.degree.grantorTexas State University
thesis.degree.levelMasters
thesis.degree.nameMaster of Science

Files

Original bundle

Now showing 1 - 1 of 1
Thumbnail Image
Name:
BRACEY-THESIS-2018.pdf
Size:
7.02 MB
Format:
Adobe Portable Document Format
Download

License bundle

Now showing 1 - 2 of 2
No Thumbnail Available
Name:
LICENSE.txt
Size:
2.13 KB
Format:
Plain Text
Description:
Download
No Thumbnail Available
Name:
PROQUEST_LICENSE.txt
Size:
4.53 KB
Format:
Plain Text
Description:
Download

Collections

Graduate Theses and Dissertations