Structural and energetic properties of the potential HIV-1 reverse transcriptase inhibitors d4A and d4G: a comprehensive theoretical investigation
| Authors | |
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| Year of publication | 2014 |
| Type | Article in Periodical |
| Magazine / Source | Journal of Biomolecular Structure and Dynamics |
| MU Faculty or unit | |
| Citation | |
| Web | http://www.tandfonline.com/doi/full/10.1080/07391102.2013.789401#.UoYzdScXeSk |
| Doi | http://dx.doi.org/10.1080/07391102.2013.789401 |
| Field | Physical chemistry and theoretical chemistry |
| Keywords | 2 ' 3 ' -didehydro-2' 3 ' -dideoxyadenosine; 2 ' 3 ' -didehydro-2 ' 3 ' -dideoxyguanosine; d4A; d4G; conformational analysis; hydrogen bonds; H-bonds; biological activity; nucleoside reverse transcriptase inhibitors; density functional theory |
| Description | A comprehensive quantum-chemical investigation of the conformational landscapes of two nucleoside HIV-1 reverse transcriptase inhibitors, d4A and d4G, has been performed. Both nucleosides are shaped by a sophisticated network of specific noncovalent interactions, including conventional OH_O, NH_O and weak CH_O, CH_N hydrogen bonds, as well as dihydrogen CH_HC contacts. For the OH_O, NH_O, and CH_O hydrogen bonds, natural bond orbital analysis revealed hyperconjugative interactions between the oxygen lone pairs and the antibonding orbital of the donor group. For the CH _HC contacts, the electron density migrates from the antibonding orbital, corresponding to the CH group of the sugar residue, to the bonding orbital relative to the same group in the nucleobase. The results confirm the current belief that the biological activity of d4A and d4G is connected with the termination of the DNA chain synthesis. Thus, these nucleosides act as competitive HIV-1 reverse transcriptase inhibitors. |
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