Iztok Prislan (University of Ljubljana)

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Location: 127 Nieuwland Science Hall

"Kinentics Says Jump, G-quadruplexes Say How High"

 

Guanine-rich sequences found in telomeric DNA can self-associate to form variety of quadruplex structures. Their formation has been found to inhibit the activity of the enzyme telomerase required for the proliferation of about 80% of cancer cells so they constitute a promising target for drug design [1]. G-quadruplexes routinely adopt multiple conformations in solution that may undergo kinetically overned interconversions and folding/unfolding transitions [2]. To better understand thermodynamics and kinetics of G-quadruplex formation, we followed thermally induced folding/unfolding transitions of d(G4T4G3) quadruplexes in Na+ and K+ solutions and tried to interpret them in terms of a kinetically governed coexistence of several quadruplex structures and their unfolded forms. We used the experimental data obtained from DSC, CD and Gel electrophoresis to develop a model which allowed us to describe folding and unfolding processes followed by DSC with a single set of parameters. Fitting of the model function to experimental data resulted in positive activation energy for all steps predicted by the model [3,4].


References:
1. Huppert,J.L. Chem. Soc. Rev., 2008, 37, 1375-1384
2. Lane,A.N., Chaires,J.B., Gray,R.D. and Trent,J.O. Nucleic Acids Res., 2008, 36, 5482-5515.
3. Prislan, I., Lah, J. and Vesnaver, G., J. Am. Chem. Soc., 2008, 130, 14161–14169.
4. Prislan, I., Lah, J., Milanic, M. and Vesnaver, G., Nucleic Acids Res., 2011, 39, 1933–1942.

 

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