A Biophysical Study of Small Molecule-Nucleic Acid Interactions

Nucleic acids are the biomolecules that encodes all the genetic information necessary for cellular metabolism. Binding of small molecules to DNA or RNA can alter their structures; perturb their functions as well as interactions with proteins and other ligands. This thesis focuses on the biophysical study of the interactions of three planar compounds with TAR 32 DNA (32 ntds DNA in HIV-1 LTR, Figure. The purpose for this study is to understand the binding modes of some of the potential drug target compounds, which will be useful for future rational drug design strategies.;Three small compounds interactions with DNA and RNA were investigated using UV-Visible, 1D NMR, Circular Dichroism and Gel electrophoresis. In investigating the small compounds and Nucleic acids interactions, our initial goal is to establish whether the compounds are intercalators or groove binders. UV spectra were collected of the compounds when they were titrated with single stranded and double stranded DNA and RNA, 1D imino proton NMR spectra were used to monitor the titration of compounds into the nucleic acids. Biophysical study showed that the compounds intercalate with nucleic acids, some better than others.;TDP-43 (RNP), which has been identified to play roles in diseases like cystic fibrosis and neurodegenerative diseases, binds to part of the TAR32 DNA sequence used for our study. If compounds bind to TAR32 DNA, possible inhibition of TDP-43 binding to TAR32 DNA is expected. The binding study of the protein with DNA in presence of compound is the topic for future research, which can be useful for future drug design strategies for neurodegenerative diseases.