Structure of a dideoxynucleoside active against the HIV (AIDS) virus

Gulbis, Jacqueline M.; Mackay, M. F.; Holan, G.; Marcuccio, Sebastian M.

doi:10.1107/s0108270193002094

Cited by 8 publications

(6 citation statements)

References 8 publications

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“…X-ray studies , of these nucleosides have shown that the glycosylic torsion angle is in anti orientation, with this geometry stabilized by the formation of self-associated species. It is also known that there exists a preference for the anti conformer for biological activity …”

Section: Resultsmentioning

confidence: 99%

Simulation of the First Hydration Shell of Nucleosides D4T and Thymidine: Structures Obtained Using MP2 and DFT Methods

et al. 2009

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A comparative theoretical analysis on the effect of the solvent on the molecular structure and energetics of the most stable conformers of the nucleoside analogue D4T (stavudine) and of the natural nucleoside thymidine (Thy) was carried out. Solvent effects were considered using the Tomasi's polarized continuum model (PCM) and including a variable number (1-13) of explicit water molecules surrounding the nucleoside in order to simulate the first hydration shell. More than 200 cluster structures with water were analyzed. B3LYP and MP2 quantum chemical methods were used. The CP-corrected interaction energies for D4T and water molecules were computed. For cases where literature data are available, the computed values were in good agreement with previous experimental and theoretical studies. In the isolated state, conformer I (anti-gg-gg) appears the most stable for D4T molecule and conformer II (anti-gg-gt) for Thy molecule. In D4T with eight water molecules, conformer II changes to conformer I. Thus, conformer I seems preferred when water molecules are situated in the first hydration shell. However, in hydrated thymidine conformer Ia (anti-gg-tg) is the more stable one, and the first hydration shell is more extended than in D4T molecule. The effect of the hydration on the total atomic charges and intermolecular distances were also discussed. Several general conclusions on hydrogen bonds network and involved interaction energies were underlined.

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Section: Resultsmentioning

confidence: 99%

Simulation of the First Hydration Shell of Nucleosides D4T and Thymidine: Structures Obtained Using MP2 and DFT Methods

et al. 2009

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“…Generally, in the progress from the syn to the anti form, the furanose ring conformer is not affected. X-Ray studies 52,53 of the nucleosides have shown that the w angle is in anti orientation and their geometries are stabilized by the formation of self-associated species. The preference for the anti conformer is necessary for biological activity.…”

Section: D4t In An Isolated Statementioning

confidence: 99%

Tautomerism of the natural thymidine nucleoside and the antiviral analogue D4T. Structure and influence of an aqueous environment using MP2 and DFT methods

Palafox

Iza

2010

Phys. Chem. Chem. Phys.

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A comparative theoretical conformational analysis of the tautomerism of the four most stable conformers of the antiviral analogue D4T (stavudine) and natural thymidine (Thy) nucleosides was carried out, by using the B3LYP and MP2 quantum chemical methods. The calculated structure data and energy values of the tautomers were compared with the T1 keto form and with the results determined for the thymine molecule. For each conformer, only two stable enol forms, T3 and T5, were obtained when considering different positions of hydrogen around the base. Tautomer T3 always appears more stable than T5, and more stable in the natural nucleoside Thy than in thymine or in D4T.The effect of water on the tautomers was estimated by using an explicit number of up to five water molecules to surround the nucleoside, and also by Tomasi's polarized continuum model (PCM). A total of about 200 clusters were optimised and the geometrical parameters and energies discussed. The water net differs in the three tautomers of D4T and Thy. Depending on the nature of the tautomers, cyclic, distributed water molecules, or clustered structures are formed. The deformation and interaction counterpoise (CP)-corrected energies between the nucleoside and water molecules were determined. The relative stabilities of all tautomers were established. The microhydrated environment stabilizes remarkably the enol forms more than the canonical keto one, although this one continues being the most stable. The changes in the intramolecular H-bondings and in the total atomic charges were discussed. Intramolecular H-bonds being stronger in D4T than in Thy could indicate a higher molecular flexibility for Thy.

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“…In these studies, as well as in others X-ray studies [67,68] of related nucleosides, the torsional angle  is always in anti orientation. The optimized thymine ring structure of the molecule is almost planar, in agreement with its experimental X-ray data available [69], and with that determined theoretically [70], as well as that reported by gas-phase electron diffraction in uracil molecule [71].…”

Section: Geometry In the Solid Statementioning

confidence: 67%

FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

Palafox

Kattan

Afseth

2018

Journal of Molecular Structure

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Structure of a dideoxynucleoside active against the HIV (AIDS) virus

Abstract: Abstract.

Cited by 8 publications

References 8 publications

Simulation of the First Hydration Shell of Nucleosides D4T and Thymidine: Structures Obtained Using MP2 and DFT Methods

Simulation of the First Hydration Shell of Nucleosides D4T and Thymidine: Structures Obtained Using MP2 and DFT Methods

Tautomerism of the natural thymidine nucleoside and the antiviral analogue D4T. Structure and influence of an aqueous environment using MP2 and DFT methods

FT-IR spectra of the anti-HIV nucleoside analogue d4T (Stavudine). Solid state simulation by DFT methods and scaling by different procedures

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