Role of Alkali Metal Ions in G-Quadruplex Nucleic Acid Structure and Stability

G-quadruplexes are guanine-rich nucleic acids that fold by forming successive quartets of guanines (the G-tetrads), stabilized by intra-quartet hydrogen bonds, inter-quartet stacking, and cation coordination. This specific although highly polymorphic type of secondary structure deviates significantly from the classical B-DNA duplex. G-quadruplexes are detectable in human cells and are strongly suspected to be involved in a number of biological processes at the DNA and RNA levels. The vast structural polymorphism exhibited by G-quadruplexes, together with their putative biological relevance, makes them attractive therapeutic targets compared to canonical duplex DNA. This chapter focuses on the essential and specific coordination of alkali metal cations by G-quadruplex nucleic acids, and most notably on studies highlighting cation-dependent dissimilarities in their stability, structure, formation, and interconversion. Section 1 surveys G-quadruplex structures and their interactions with alkali metal ions while Section 2 presents analytical methods used to study G-quadruplexes. The influence of alkali cations on the stability, structure, and kinetics of formation of G-quadruplex structures of quadruplexes will be discussed in Sections 3 and 4. Section 5 focuses on the cation-induced interconversion of G-quadruplex structures. In Sections 3 to 5, we will particularly emphasize the comparisons between cations, most often K⁺ and Na⁺ because of their prevalence in the literature and in cells.