Document Type
Thesis
Date of Award
2004
Degree Name by School
Master of Science (MS) Heersink School of Medicine
Abstract
The thermodynamic effects of alterations of the DNA duplex by DNA base modifications or ligand binding are investigated by a combination of spectrophotometric and calorimetric methods. Examination of the effects of substituent modification on the DNA binding energetics of the anticancer agent AAC (Y-[2-(dimethylamino)ethyl]-9-aminoacridine-4-carboxamide) indicated that DNA binding affinities and energetics were enhanced upon substitution at the C5 position on the chromophore of the drug with a variety of chemical groups. A correlation between enthalpies of DNA binding and anticancer activity was evident.The impacts of DNA base modifications, including cytosine arabinoside, deaminated cytosine, and abasic sites, on the thermodynamics of duplex formation and transition and duplex thermal stability indicated a modification-induced destabilization of the double helix. The effects of cytosine arabinoside modifications on the DNA duplex were further investigated by examining the effects of cytosine arabinoside on duplex hydration using the osmotic stress method. An equivalent hydration of the unmodified and cytosine arabinoside-modified duplexes was evident. Results of the thermodynamic consequences of ligand-DNA interactions and DNA base modifications are related to their ability to modulate the activity of the essential cellular enzyme topoisomerase II.
Recommended Citation
Graves, Rachel Hutchins, "Thermodynamic Consequences of DNA Base Modifications and Ligand-DNA Interactions." (2004). All ETDs from UAB. 6931.
https://digitalcommons.library.uab.edu/etd-collection/6931
Comments
MS - Master of Science/Master of Surgery; ProQuest publication number 31751851