NMR Studies on the syn‐anti Dynamic Equilibrium in Purine Nucleosides and Nucleotides

Abstract

The s.yn + anti equilibrium conformation about the glycosidic bond of purine nucleosides and 5'-nucleotides in different solvent systems has been investigated by means of 'H NMR spectroscopy. Quantitative values for the conformer populations were improved, relative to previous results, by a detailed study of, and a resultant derived correction for, the influence of the sugar exocyclic group carbons were employed to evaluate approximately the glycosidic angles x of the nucleosides in the conformations s,yn and anti. A critical examination is made of the applicability of relaxation methods, involving analysis of spin-lattice relaxation time of protons ( T I ) and the Overhauser effect, to determine the conformation of the base about the glycosidic bond; interpretations are provided for the lack of agreement between these methods and those based on chemical shifts in the present study. The foregoing results are also applied to an examination of the effect of the conformation of the base about the glycosidic bond on the enzymatic reactions catalyzed by 5'-nucleotidase and adenosine deaminase.We have previously described a procedure [l] for evaluation of the syn-anti conformer populations in nucleosides from the chemical shifts of the sugar protons, in particular of H-2'. Under conditions where there is a rapid exchange, on the N M R time-scale, between these two conformations, the observed chemical shift of H-2' is the mean of those for the fixed conformations syn and anti: dsVn and d o n t i , fiobs = Psyn d s y n + Punri d u n t i

Insights into the Mechanism of Bovine CD38/NAD+Glycohydrolase from the X-Ray Structures of Its Michaelis Complex and Covalently-Trapped Intermediates

“…Only an adenosine moiety adopting the energetically unfavorable syn conformation would allow the adenine ring stacked against Trp181, to be positioned into a ‘near-attack conformation’ [73] resulting in the formation of cADPR. However, our structural studies show that the anti conformation, which is favored thermodynamically [59], [74], is also stabilized by specific interactions with the active site of bCD38. It thus seems that the design of the active site of CD38 is not optimized to make cADPR and that formation of this important metabolite rather results from a stochastic conformational choreography.…”

An Unusual DNA Adduct Derived from the Powerfully Mutagenic Environmental Contaminant 3-Nitrobenzanthrone

“…For the 1 H and 13 C NMR characterization of the adducts, JEOL-JNM-A500 (500 MHz for 1 H NMR) and JEOL-JNM-LA300 (75. 45 MHz for 13 C NMR) spectrometers were used. Electron impact mass spectra (EI-MS) were recorded on a Shimadzu GC-MS QP-2000A spectrometer at 70 eV and chemical ionization mass spectra (CI-MS) on a Shimadzu GC-MS QP-5000 spectrometer with DI-50 using isobutane as a reacting gas.…”

Binding of Nucleotides and Nucleosides to Per(6‐guanidino‐6‐deoxy)cyclodextrins in Solution

“…son of chemical shifts, [12][13][14] vicinal spin-spin coupling constants, [15] 1D nuclear Overhauser enhancements, and nuclear relaxation rates, [16] as well as the effects of lanthanide cation probes (Ln 3+ ) [17] on chemical shift and relaxation rates, were analyzed. Comparison of chemical shifts indicated a dynamic syn h anti equilibrium with a preference for the anti conformation (≈70 %) in nucleosides, whereas there was a dominance for the anti conformation (virtually 100 %) in nucleotides.…”