ISSN:
1434-1948
Keywords:
Nucleotides
;
Conformation analysis
;
NMR spectroscopy
;
Pseudorotational equilibrium
;
Anomeric effect
;
Chemistry
;
General Chemistry
Source:
Wiley InterScience Backfile Collection 1832-2000
Topics:
Chemistry and Pharmacology
Notes:
A conformational study is reported on 2′-deoxyguanosine 5′-methylmonophosphate [MepdG (1)] and 2′-deoxyguanosine 3′-methylmonophosphate [dGpMe (2)] and their interactions with Mg2+, Zn2+ and Hg2+ ions. The conformation of MepdG (1) and dGpMe (2) in D2O solution was inferred from vicinal proton-proton, proton-phosphorus and carbon-phosphorus NMR coupling constants and nuclear Overhauser effects (NOE). The chemical shift changes showed that hard Mg2+ ions interact preferentially with the phosphate oxygen atoms in MepdG (1), whereas in the case of dGpMe (2) the interaction with the phosphate oxygen atoms competes with the interaction to the C6=O carbonyl group. Softer Zn2+ and Hg2+ ions were found to show strong binding affinity towards N7 in both MepdG (1) and dGpMe (2). Analysis of J coupling constants and NOEs measured as a function of metal ion concentration revealed that: (i) N → S pseudorotational equilibria are biased towards C2′-endo pseudorotamers in M2+-free MepdG (1) and dGpMe (2) by 68% and 75% at 298K, respectively. Titration of MepdG (1) and dGpMe (2) with Mg2+ ions caused no observable changes in N → S pseudorotational equilibrium, whereas the interactions of Zn2+ and Hg2+ ions with N7 resulted in the shift towards N-type pseudorotamers which can be explained by the strengthening of the anomeric effect as softer metal ions bind to N7 and make the imidazole moiety less electron-rich. (ii) The binding of divalent metal ions to MepdG (1) and dGpMe (2) causes a shift of the syn → anti equilibrium towards anti, which is larger for softer Zn2+ than for harder Mg2+ ions. (iii) The conformational equilibrium across the C4′-C5′ bond (γ torsion) in dGpMe (2) is not affected by the increased concentration of M2+ ions. (iv) βt conformers are preferred by ca. 77% in aqueous solution of MepdG (1) and only small changes of ca. 1 percentage point in βt population have been found upon metal ion binding to MepdG (1). (v) The two-state εt → ε- conformational equilibrium is biased towards εt rotamers by 63.5% in dGpMe (2). Interaction of hard Mg2+ and softer Zn2+ or Hg2+ ions with dGpMe (2) resulted in the minor increase (〈 3 percentage points) in the population of εt conformers.
Additional Material:
4 Ill.
Type of Medium:
Electronic Resource
