Date of Submission

Spring 2018

Academic Programs and Concentrations

Chemistry

Project Advisor 1

Swapan Jain

Abstract/Artist's Statement

Telomere shortening is primarily involved in cell death and cellular aging. However, telomerase can reverse the shortening process and allow cells to overcome apoptosis. Telomerase activity is expressed in 85-90% of cancer cells. Binding of this enzyme can be prevented by the formation of G-quadruplex structures, which include stacks of G-tetrads formed by telomeric TTAGGG tandem repeats. Therefore, G-quadruplex stability is crucial to the inhibition of telomerase activity and ligand-induced quadruplex stabilization emerges as a potential chemotherapeutic pathway due to its high selectivity and specificity towards cancer cells.

Our project aims to understand the stabilization mechanism of DNA/RNA G-quadruplex by organometallic compounds using UV/Vis spectroscopy and Isothermal Titration Calorimetry (ITC). We have shown that quadruplex stability is increased by potassium ions and further enhanced by the cationic porphyrin ligands TMPyP4 and Mn(III) TMPyP4. We also found that the anionic copper (II) phthalocyanine Cu-APC complex, discovered by the Sugimoto group, potentially interacts with both DNA and RNA quadruplexes. The nonionic benzothiophene platinum(II) complex L3, synthesized by the Anderson lab, also interacts with DNA G- quadruplex and potentially stabilizes the structures. Our studies have provided insights into improving quadruplex stability by organometallic ligands and how their stabilizing effects differ due to structural differences.

Open Access Agreement

On-Campus only

Creative Commons License

Creative Commons License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 4.0 License.

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