CHAPTER 17: Thermodynamics of the Folding and Interconversion of G-quadruplex DNA Structures

In 1953, Watson and Crick presented their iconic structure of double-stranded DNA. However, DNA may adopt other structures that appear only in specific contexts. Widely recognized are the so-called G-quadruplexes (G4) formed from G-rich sequences in the presence of specific cations. These structures have been extensively studied, e.g. their role in gene regulation and their links with diseases such as cancer, Alzheimer's disease and diabetes are areas of extensive research. In recent years, progress has been made in understanding why guanine-rich sequences fold into different intermediate and folded G4 structures and why they interconvert between themselves depending on temperature and concentrations of co-solvents, co-solutes and ligands. In this chapter, it is shown how the relevant thermodynamic and sometimes also kinetic parameters are obtained employing spectroscopic and calorimetric techniques using an appropriate model analysis of experimental data. It is demonstrated how the parameters obtained can be interpreted in terms of the thermodynamic driving forces accompanying the G4 folding/interconversion and how they are translated into phase diagrams that provide an elegant description of the G4 phase space over a wide range of solution conditions.