Proton-Magnetic-Resonance Study of the Solution Conformation of the alpha and beta Anomers of 5-Ethyl-2'-deoxyuridine

Abstract

1. The a and /3 anomers of 5-ethyl-2'-deoxyuridine, the latter of which is a thymidine analogue with antiviral activity, have been subjected to a conformational analysis in aqueous medium by proton magnetic resonance (PMR) spectroscopy with the aid of the iteration program 2. The results demonstrated a marked preference for the conformation C-2'-endo of the deoxyribose rings of both anomers; and this appears to be an inherent property of the deoxyribose ring itself. As regards the exocyclic 5'-CH20H group, the /3 anomer exhibited a preference for the gaucheguuche conformation ; in the case of the a anomer, all three classical conformers were equally favoured.3. A particularly extensive analysis of the conformation about the glycosidic bond, based on the chemical shifts of several sugar protons, pointed to the conformation anti for both anomers.4. The data for the protons of the 5-ethyl side chain are in accord with a symmetrical distribution of the rotamers of this substituent relative to the plane of the pyrimidine ring.5. The overall findings are compared with those earlier reported for the CI and /3 anomers of thymidine, as well as a number of other nucleosides, nucleotides and polynucleotides.6. PMR spectral data were similarly utilised to perform a conformational analysis of the cx and fl anomers of 5-ethyl-2'-deoxycytidine, an analogue of 5-methyldeoxycytidine ; the results did not differ appreciably from those for the 5-ethyldeoxyuridine anomers.It has been shown that 5-ethyluracil is a thymine analogue and will partially replace thymine in a thymine-less strain of Escherichiu coli [l], while 5-ethyldeoxyuridine readily substitutes for thymidine in phage T3 DNA [2]. The resulting DNA exhibits a T, somewhat lower than that for the corresponding thymine-containing DNA, in agreement with the destabilizing effect of a 5-ethyl substituent, relative to a 5-methyl, in several synthetic polynucleotide systems [3,4]. Furthermore 5-ethyldeoxyuridine exhibits appreciable antiviral activity against herpes simplex and vaccinia viruses [5,6].5'-Ethyldeoxyuridine differs from numerous other thymidine analogues, such as the commonly employed 5-bromodeoxyuridine, in that its pK (for dissociation of the pyrimidine N-3 hydrogen, which is the donor Ahhrrviutions. PMR, proton magnetic resonance. The terms "endo" and "exo" are employed with their usual connotations to indicate the deviation of a given furanose ring atom above or below the best plane of the remaining furanose ring atoms, by FZ 10-20 pm; "endo" and "exo" refer to analogous deviations of FZ 50-60 Pm.in Watson-Crick base pairing) is virtually identical with that for thymidine [3]. Replacement of thymine by 5-ethyluracil in synthetic or natural polynucleotides is therefore not accompanied by major modifications due to electrostatic effects.It consequently appeared of interest to examine the conformation of 5-ethyldeoxyuridine in aqueous medium. The availability of the a anomer of this nucleoside prompted a parallel study of its conformation, thus making possible a...

Principles of Nucleic Acid Structure

“…For the C4,-CS' bond, however, the preponderance of the sc conformation is less obvious than in the J3-nucleosides, a result indicated by the available crystallographic data [references in (664)] and by solution studies using nuclear magnetic resonance spectroscopy (638,665,666). In terms of intramolecular interactions, these findings suggest that the Os' ... H-C(base) interactions discussed in Section 4.9 are the main fac- tors pulling the Os' hydroxyl into the preferred sc orientation.…”

NMR study of stacking interactions and conformational adjustments in the dinucleotide-carcinogen adduct 2'-deoxycytidylyl-(3 .fwdarw. 5)-2'-deoxy-8-(N-fluoren-2-ylacetamido)guanosine

“…The 5 ' and 5'' resonances of the deoxyguanosine moiety (G5' and G5") of d-Cp(AAFG) and d-p(AAFG) were assigned from stereochemical considerations. The corresponding protons of the deoxycytidine moiety (C5' and CY') have been tentatively assigned according to the Remin-Shugar method (Remin & Shugar, 1972). The 13C resonance assignments for d-Cp-(AAFG) are based on chemical shift and spectral comparisons with d-p(AAFG) (Evans et al, , 1986 and other model compounds (Alderfer, 1984).…”

Alterations in the d(CpGpT) structure in solution as a result of [PtCl(diethylenetriamine)]+ binding

“…The H5' and the H5" resonances were assigned according to Remin and Shugar [35], i.e. the H5" signal is located upfield relative to the H5' signal.…”