Stimuli Mediated Conformational Transitions and Detection of Different Secondary Structures of DNA

Abstract

Since the DNA double helix discovery in 1953 by Watson and Crick, an extensive improvement in the understanding of DNA secondary structure has been observed. Apart from the canonical double helix structure, DNA can show its polymorphism by means of folding into various other inter- and intra-molecular secondary structures like tetraplex (G-quadruplex and i-motif), A-motif, hairpin, triplex (H-DNA), sticky DNA, left-handed Z-DNA, cruciform, etc. Importantly, these unusual DNA structures have been often found to participate in many biologically important processes including genome recombination, cancer cell immortality and regulation of gene expression, which I have discussed in details in chapter 1. Understanding the molecular mechanism behind the formation and activity of these different secondary structures always has been the point of interest among researchers which can be utilised for further biomedical, materials and nanotechnological applications. In my PhD, we have tried to control the conformational transitions of different DNA secondary structures by using some external stimuli keeping the potential future biomedical applications in mind. In chapter 2, we have investigated an ionic liquid induced DNA compaction phenomenon (coil to globule transitions). In chapter 3A, we have explored the formation and stabilisation of a non-canonical DNA structure, i.e. G-quadruplex DNA (GQ DNA), and in chapter 3B, we have applied a unique strategy to control the formation of GQ DNA by incorporating the reversibility aspect in the transition. In chapter 4A, we have demonstrated a reversible approach to stabilise another tetraplex DNA, i.e. i-motif DNA in neutral and alkaline medium, unlike its characteristics by incorporating it into silica nano-channels. In chapter 4B, we have developed an i-motif sensor, selective to i-motif DNA over its complementary analog, i.e. GQ DNA unlike the reported ones in literature. Additionally, we have tried to decipher the structure-property relationship between i-motif and its ligands which will be necessary for the future designing of new i-motif ligands/sensors.