Conformational properties of purine-pyrimidine and pyrimidine-purine dinucleoside monophosphates

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Abstract
The detailed conformational features and dynamics of heterodinucleoside monophosphates ApU, ApC, GpU, GpC, UpA, CpA, UpG and CpG were studied in aqueous solution by high field NMR spectroscopy. Analysis of the resultant NMR parameters leads to a number of discernible trends throughout the series. Thus the ribose rings of the dimers exist as equilibrium mixtures of C(2'')-endo(2E) .dblarw. C(3'')-endo(3E) conformers with a proclivity for the 3E pucker in most cases; the C(4'')-C(5'') bonds of both nucleotidyl units show significant preference (74-96%) for a gg conformation and the dominant conformer (85-89%) about C(5'')-O(5'') is g''g''. Orientation about the C(3'')-O(3'') bond is coupled to the ribose conformational equilibrium and the system exists with a bias for the 3Eg- coupled conformation in which the H(3'')-C(3'')-O(3'')-P dihedral angle occupies the narrow range of 33-35.degree.. Dimerization, on the average, causes about 10% increase in gg and g''g'' populations and the g- domain becomes increasingly populated about the C(3'')-O(3'') bond. The ribose equilibrium 2E .dblarw. 3E shifts in favor of 3E on dimerization, the effect being very conspicuous for the pu-py (purine-pyrimidine) series .apprx. 40 .fwdarw. 60%) and less noticeable for the py-pu systems (.apprx. 47 .fwdarw. 58%), clearly suggesting a correlation between sequence and ribose conformational equilibrium. The temperature and dimerization data for the heterodinucleoside monophosphates show that the transition 2E .fwdarw. 3E is directly related to .chi. CN changes induced by dimerization and stacking. Analysis of the ribose coupling data shows that the percentage populations of stacked species vary from dimer to dimer with GpC displaying a maximum of 45% stacked population and UpG about 10%. In general, the pu-py dimers show a higher preference (27-45%) for stacked conformations than py-pu dimers (10-25%). The pronounced deshielding of H(5'') of the 5''-nucleotidyl units on dimerization may be associated with the presence of right-handed stacks (g-g-), whereas the chemical shift trends of H(5'') and H(5") of 3''-nucleotidyl units are probably due to the presence of left-handed stacks (g+g+) in all the dimers. In pu-py dimers, the population of the g-g- species is greater than that of g+g+. Also the population of g-g- stacks in pu-py dimers is generally greater than in their corresponding matched py-pu dimers. Thus the base sequence has not only an explicit effect on the overall populations of the stacked species, but also on the handedness of the stacks. The present results further confirm the interdependence of conformational bonds throughout the nucleotidyl framework.

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