Structural motifs of the nucleotidyl unit and the handedness of polynucleotide helices

The nucleotide building blocks of nucleic acids show a preference for two major conformational motifs mainly determined by the sugar puckering and the concerted changes in the glycosyl sugar‐base torsion angle: 3 E‐low anti (χ) and 2 E‐high anti (χ). The backbone C4′C5′ bond torsion prefers the gauche 1 range while the C5′O5′ torsion displays a somewhat broader trans range. Thus the two preferred sugar‐base‐backbone relationships are: 3 E‐anti‐gauche + and 2 Eanti‐ gauche + . In 5′‐nucleotides there is an extreme reluctance for the syn base. Guanine is notoriously peculiar and has a tendency for syn. When the base is syn, the steric conflict with the phosphate is relieved by a concerted rotation around the C4′C5′ bond to the trans (or gauche − ) states, leading to three additional nucleotide motifs: 3 E‐syn‐trans and 3 E‐syn‐trans (or gauche − ). The gauche − state is highly destabilized for the 3 E. , Superhigh χ's are known to drive the backbone into left‐handed structures, as exemplified by the unnatural Ikehara polymers [M. Sundaralingam and N. Yathindra, Int. J. Quantum Biol. QB4 , 285–303 (1977)]. In the recently discovered left‐handed Z helices of the alternating deoxy‐CG tetra‐ and hexanucleotides it may be regarded that the C residues assume the preferred “right‐handed” conformational combination 2 E‐anti‐gauche + , while the G residues assume the less favored “left‐handed” combination 2 E‐syn‐trans. , In the latter, steric interactions between the syn base and the 5′‐phosphate drive the C4′C5′ torsion into the trans range , and the electrostatic interactions between the syn base and the 3′‐phosphate now drive the sugar into 2 E (a variant of 3 E). The departure from the preferred nucleotide conformations leads to correlated changes in the ester P′O bonds of the internucleotide phosphodiester groups, which alternatively adopt (in Z‐DNA) the “left‐handed” double gauche (gauche + , gauche + ) and the “right‐handed” (gauche′, trans) conformations. The pseudorotational mobility of the furanose ring provides a simple and elegant way of understanding conformational fluctuations and flexibility of nucleic acids. Thermal fluctuations capitalize on the pseudorotation property of the furanose ring. Because the furanose ring is linked to the base and the phosphate, these fluctuations are correlated to the rotational mobility of the base and the phosphate and lead to phenomena such as premelting changes, breathing modes, or opening of base pairs. Such motions are instrumental in the polymorphic transitions of nucleic acid helices (e.g. A ⇄ B, B ⇄ C, B ⇄ Z, …) or in functional processes, such as unwinding and fork formation. It is also proposed that concerted changes in the sugar‐phosphate backbone torsion angles, akin to a crankshaft motion, can bring about the B ⇄ Z transition without necessarily disrupting the hydrogen bonds.