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3 Stability of Non-canonical Nucleic Acids
The main points of the learning:
1 Study the interactions to determine the stability of canonical nucleic acids.
2 Understand the difference in factors determining stability of canonical and non-canonical nucleic acids.
3 Analyze the stability for canonical and non-canonical nucleic acids.
3.1 Introduction
It is important to understand the stabilities of both canonical and non-canonical nucleic acids for estimating nucleic acid structures and functions in vitro and in cell. In this chapter, the stabilities of non-canonical nucleic acids are introduced with comparison of the difference from those of the canonical duplex. In general, the following factors play major roles in determining the stabilities of nucleic acids: hydrogen bonding, base stacking, conformational entropy, hydration, and cation binding. Hydrogen bonding, base stacking, and conformational stress are determined by sequence of nucleic acids [1]. In contrast, the water and cation bindings are determined by conditions surrounding the nucleic acid such as cosolute and cosolvent conditions that are described next in Chapter 4 in detail [2]. Thus, this chapter surveys the factors influencing the stabilities of nucleic acids depending on sequences and their environments. Moreover, this chapter describes methods that can be used to analyze quantitatively the stabilities of the nucleic acids. To understand the basic factors influencing stabilities of the nucleic acids, the stability of duplexes is explained, and then the non-canonical structures and their stability are described.
3.2 Factors Influencing Stabilities of the Canonical Duplexes
3.2.1 Hydrogen Bond Formations
Three factors are mainly responsible for the stability for the canonical structure of duplex: base pairing between complementary strands, stacking between adjacent bases, and conformational entropy of the backbone.
Electronegative O and N atoms with free lone pairs are potential hydrogen bond acceptors. Hydrogen atoms that have strong partial positive charge and are potential hydrogen bond donors bind to electronegative atoms such as O and N. Many of the oxygen, nitrogen, and hydrogen atoms in the nitrogenous bases are very effective hydrogen bond donors and acceptors, as illustrated in Figure 3.1. Adenine (A) and thymine (T) form base pairs via hydrogen bond donors and acceptors, and the A-T base pair has two hydrogen bonds between the bases. Cytosine (C) and guanine (G) similarly form base pairs with three hydrogen bonds (Figure 3.2a). The values of free energy change at 37 °C (−Δ