Type of Document Dissertation Author Rahimian, Maryam Author's Email Address mrahimian1@student.gsu.edu URN etd-10282008-071339 Title BINDING, BENDING AND G JUMPING IN THE MINOR GROOVE: EXPERIMENTAL AND THEORETICAL APPROACHES Degree Ph.D. Department Chemistry Advisory Committee
Advisor Name Title Dr. W. David Wilson Committee Chair Dr. David W. Boykin Committee Member Dr. Donald Hamelberg Committee Member Dr. Stuart A. Allison Committee Member Keywords
- Circular dichroism
- Cooperativity
- G jumpers
- Minor groove binders
Date of Defense 2008-09-26 Availability restricted Abstract It has been shown that heterocyclic diamidines, a class of minor groove binders, are promising antimicrobial agents. These compounds bind none covalently to the minor groove of A/T rich regions of the kinetoplast DNA and kill the parasite. The mechanism of action of these compounds is not well understood, yet many hypotheses have been proposed. One of the methods that improve the specificity is cooperative binding. Since there are many binding sites available in k-DNA thus the cooperativity in adjacent binding sites is desirable. A library of compounds has been scanned and few of those compounds identified that are able to bind to two adjacent A/T binding sites separated by a single G. Many biophysical methods such as isothermal titration calorimetry, surface Plasmon resonance, circular dichroism and thermal melting have been used to explore the thermodynamic profiles and binding mode of these compounds. The pulsed field gradient NMR was used to investigate the structural changes to the DNA sequence upon binding of the minor groove binders and find a correlation between their biological difference and structural changes. The molecular dynamics was applied to look at the interaction of some of the heterocyclic diamidines to the DNA with more details and predict the unknown structures.Files
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