Conformational studies on polynuc leotides and nucleic acids

Abstract

After an introduction to the nucleic acids and the conformational studies on them at the monomeric and polymeric levels, the need for investigations on the conformations of 3?-nucleotides is outlined. The significance of such an analysis on the understanding of polynucleotide double-helical structures has been brought out. It is found that 3?-nucleotides are indeed flexible with the torsion about the O3?–O3* bond taking up gauche conformations in addition to the conventional trans conformations. Further, towards appreciating the role played by the flexibility of nucleotides in determining polynucleotide structures, conformational analysis of 5?-nucleotides has also been carried out. These studies emphasize the significance of the flexibility of the sugar ring in addition to that exhibited by the other conformational parameters of the nucleotide unit. The salient features of the energetics studies on nucleotides have been incorporated into the stereochemical criteria, which provide input conformational parameters for model-building studies. It is found that only a limited number of classes of the backbone conformational parameters are meaningful from the viewpoint of polynucleotide double-helical structures. Further, it has been demonstrated that the nature of the sugar pucker and the glycosidic orientation of the bases are the conformational parameters which significantly influence the handedness of the base-paired double-helical structures. It has been shown that left- and right-handed base-paired double-helical structures are appropriately classified in terms of the glycosidic torsion. The implications of the flexibility of the nucleotide unit and the interrelationships between the backbone torsion angles on the structure determination of polynucleotides, both from medium-resolution crystal structure data and fibre diffraction data, are briefly discussed.