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

Abstract

The detailed conformational features and dynamics of heterodinucleoside monophosphates ApU, ApC, GpU, GpC, UpA, CpA, UpG, and CpG have been studied in aqueous solution by high field nuclear magnetic resonance (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) in equilibrium 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 degrees. 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 in equilibrium 3E shifts in favor of 3E upon dimerization, the effect being very conspicuous for the pu-py series (similar to 40 yields 60%) and less noticeable for the py-pu systems (similar to 47 yields 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 yields 3E is directly related to XCN 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%. However, in general, the pu-py dimers show a higher preference (27-45%) for stacked conformations than py-pu dimers (10-25%). It is proposed that the pronounced deshielding of H(5') of the 5'-nucleotidyl units upon dimerization is 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 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 found to be 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 stacked species, but also on the handedness of the stacks. The present results further confirm the interdependence of conformational bonds throughout the nucleotidyl framework.

Conformation and Flexibility of GpC and CpG in Neutral Aqueous Solution using 1H Nuclear-Magnetic-Resonance and Spin-Lattice-Relaxation Time Measurements

“…The assignments are in agreement with those of Ezra et al [4]. The determination of certain coupling constants between ribose protons was sometimes difficult because of the overlapping of the signals from the two ribose moieties.…”

The Synthesis of Deuterionucleosides

“…monophosphates that are useful for chemical synthesis of short oligomers by diester chemistry or are used directly in enzymatic syntheses of various short oligomers [218][219][220][221] .…”

Influence of uracil on the conformational behaviour of RNA oligonucleotides in solution

“…For example, the small populations of N-type conformer in UGUG compared to UAUA correspond to the small population of N-type sugar in the constituent dimers UG and GU compared to UA and AU, respectively. Moreover, it is known from studies on dimers [17] that the stacking properties of UA and AU are superior to those of UG and GU, respectively. Similarly, in the case of the present tetramers substitution of A for G results in a decrease of N-type sugar population and thus presumably in a decrease of nearest-neighbour stacking interaction.…”