This is a renewal application for an existing grant. This proposal aims to measure complete thermodynamic profiles including hydration effects for a variety of DNA duplexes, some with modified phosphates, and for a number of DNA or DNA/RNA duplexes with intercalated or covalently bound ligands. Experimental methods include temperature and pressure dependent UV and CD spectroscopy, high sensitivity differential scanning calorimetry, and titration calorimetry. In particular, Dr. Marky proposes: 1) to characterize the role of counterions (Cs+ ,Na+ , K+ , Mg++) in the stability of telomeric and centromeric model sequences. 2) to determine the overall hydration of hairpins (stem-loop structures) containing bulges and mismatches and to characterize hydration effects from interactions with intercalating agents. Complete thermodynamics profiles (deltaG, deltaH, delta S and deltaV) will be obtained. 3) to determine differences in thermodynamic behavior, including hydration, of DNA, RNA and mixed duplexes. 4) to thermodynamically characterize, in terms of binding mode and conformation, the hydration effects from placing covalently bound hydrophobic moieties in oligomer duplexes. 5. to obtain complete thermodynamic profiles, including heat capacity effects, for side-by-side binding of cross-linked lexitropsins to the minor groove of DNA. 6. to determine the electrostatic and hydration contributions in the formation of DNA bent structures.

National Institute of Health (NIH)
National Institute of General Medical Sciences (NIGMS)
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Special Emphasis Panel (ZRG3-BBCA (01))
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University of Nebraska Medical Center
Schools of Pharmacy
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Carr, Carolyn E; Ganugula, Rajkumar; Shikiya, Ronald et al. (2018) Effect of dC ? d(m5C) substitutions on the folding of intramolecular triplexes with mixed TAT and C+GC base triplets. Biochimie 146:156-165
Soto, Ana Maria; Gmeiner, William H; Marky, Luis A (2002) Energetic and conformational contributions to the stability of Okazaki fragments. Biochemistry 41:6842-9
Comolli, Luis R; Ulyanov, Nikolai B; Soto, Ana Maria et al. (2002) NMR structure of the 3' stem-loop from human U4 snRNA. Nucleic Acids Res 30:4371-9
Soto, Ana Maria; Loo, Jacqueline; Marky, Luis A (2002) Energetic contributions for the formation of TAT/TAT, TAT/CGC(+), and CGC(+)/CGC(+) base triplet stacks. J Am Chem Soc 124:14355-63
Soto, Ana Maria; Marky, Luis A (2002) Thermodynamic contributions for the incorporation of GTA triplets within canonical TAT/TAT and C+GC/C+GC base-triplet stacks of DNA triplexes. Biochemistry 41:12475-82
Soto, Ana Maria; Kankia, Besik I; Dande, Prasad et al. (2002) Thermodynamic and hydration effects for the incorporation of a cationic 3-aminopropyl chain into DNA. Nucleic Acids Res 30:3171-80
Kankia, Besik I; Soto, Ana Maria; Burns, Nicole et al. (2002) DNA oligonucleotide duplexes containing intramolecular platinated cross-links: energetics, hydration, sequence, and ionic effects. Biopolymers 65:218-27
Shah, D; Kelly, J; Zhang, Y et al. (2001) Evidence in Escherichia coli that N3-methyladenine lesions induced by a minor groove binding methyl sulfonate ester can be processed by both base and nucleotide excision repair. Biochemistry 40:1796-803
Soto, A M; Kankia, B I; Dande, P et al. (2001) Incorporation of a cationic aminopropyl chain in DNA hairpins: thermodynamics and hydration. Nucleic Acids Res 29:3638-45
Kankia, B I; Marky, L A (2001) Folding of the thrombin aptamer into a G-quadruplex with Sr(2+): stability, heat, and hydration. J Am Chem Soc 123:10799-804

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