Spectroscopic study on oncogene promoter I-motif's folding behavior and stability at neutral pH

Abstract

During the past decades, there has been a notable growth in the application of spectroscopic techniques in chemistry and biology sciences since spectroscopy is one of the most accessible, easy-to-use and theory-supported methods to understand biomacromolecule behavior. In this project, both steady-state and time-resolved spectroscopic techniques have been applied. Amounts of UV-Vis absorption, fluorescence and circular dichroism measurements have been taken and analyzed. Here our study of interest is i-motif's folding behavior and stability under neutral pH environment. I-motif is a four-stranded DNA secondary structure built by intercalated hemiprotonated cytosine-cytosine base pairs, which predominantly exists at slightly acidic pH. Therefore, its folding ability under physiological pH condition is a long-lasting interested issue. In 2018, this unique DNA tetraplex structure has been proved to be exist in human nuclei. Then study towards i-motif becomes an interest to many research groups. Here in this project, we first selected several natural oncogene promoter i-motifs for investigation and then focused on c-MYC i-motif, an unusual stable one at pH 7. Concerning this central i-motif, we collected and studied its absorption, fluorescence, circular dichroism and transient absorption spectroscopic characteristics and used these to analyze and explore potential factors that influence i-motif's folding, stability, and binding with small molecules. Importantly, in this project, we discovered two new factors that influence the stability of i-motif structure at neutral pH, dangling end and buffer species, observed i-motif conformer phenomenon and characterized the binding behavior between i-motif and DAPI molecule.