dc.contributor.advisor |
Marcud, Andrew |
|
dc.contributor.author |
Ji, Huiying |
|
dc.date.accessioned |
2019-04-30T21:14:12Z |
|
dc.date.available |
2019-04-30T21:14:12Z |
|
dc.date.issued |
2019-04-30 |
|
dc.identifier.uri |
http://hdl.handle.net/1794/24545 |
|
dc.description.abstract |
Understanding the local conformations of DNA at the level of individual nucleic acid
bases is important for the study of the mechanism of DNA sequence-dependent behavior.
Here we apply linear absorption, circular dichroism (CD), and fluorescence spectroscopy
to study the DNA local base conformation using 6-methyl Isoxanthopterin (6-MI) labeled
DNA. We interpret excitation–emission peak shift (EES) measurements of the 6-MI, both
as a ribonucleotide monophosphate in solution and as a site-specific substituent for guanine
in various DNA constructs, by implementing a simple two-state model. We show that the
spectroscopic properties of the 6-MI probe in DNA can be used to obtain detailed
information about local base conformations and conformational heterogeneity and
fluctuations. Based on these findings, we apply a simple theoretical model to calculate CD
of 6-MI substituted DNA constructs. We find that our model can be used to extract basesequence-
dependent information about the local conformation of the 6-MI probe as
modulated by the local base or base-pair environment. We next apply 6-MI to probe the
ligand insertion of small molecules to duplex DNA, further extending the potential of 6-
MI as a useful reporter of local nucleic acid base conformation. These studies served to
establish a new level of sophistication in qualitatively analyzing 6-MI structural behavior
in terms of local base stacking and unstacking conformations.
v
This dissertation contains previously published and unpublished co-authored
material. |
en_US |
dc.language.iso |
en_US |
|
dc.publisher |
University of Oregon |
|
dc.rights |
All Rights Reserved. |
|
dc.subject |
Fluorescence spectroscopy |
en_US |
dc.subject |
Local base conformation of DNA |
en_US |
dc.subject |
Theoretical circular dichroism calculation |
en_US |
dc.title |
Local Nucleic Acid Base Conformation Study by Guanine Fluorescent Analogue 6- Methyl Isoxanthopterin (6-MI) Labeled DNA |
|
dc.type |
Electronic Thesis or Dissertation |
|
thesis.degree.name |
Ph.D. |
|
thesis.degree.level |
doctoral |
|
thesis.degree.discipline |
Department of Chemistry and Biochemistry |
|
thesis.degree.grantor |
University of Oregon |
|