Authors:

Rio Ohtake

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MYC gene is responsible for producing transcription factor that stimulates various cellular processes and its deregulation contributes to the causes of many cancers. G-quadruplexes are non-canonical, globular intramolecular secondary structures of DNA that form in guanine-rich regions. Within the MYC promoter region, the formation of G-quadruplex results in repression of MYC expression and suppression of cancer cells. Thereby the stabilization of the MYC promoter G-quadruplex is an attractive drug target for the development of anti-cancer research. However, clinically available drugs have not been found yet. In our previous studies, a class of compounds, Indenoisoquinolines, that bind and stabilize G-quadruplexes, were discovered. This research project aimed to determine which Indenoisoquinolines stabilize the MYC G-quadruplex. Circular Dichroism spectroscopy (CD) is a commonly used technique to characterize the topology and thermal stability of G-quadruplexes. In this study, CD was used to measure the spectra curve and thermal denaturing curve of the MYC promoter DNA G-quadruplex in the presence and absence of Indenoisoquinolines to analyze how the compounds affect the topology and thermal stability of MYC G-quadruplex. This study was able to compare the melting temperature difference between the drug-free DNA and the drug-present DNA to observe the effectiveness of Indenoisoquinolines to stabilize the MYC G-quadruplex. Data from this study will be used in combination with cellular studies to understand the effectiveness of these drugs in cancer cells at repressing MYC expression.

Source:

Purdue University / 2023

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Co-authors:

Rio Ohtake