[Complete conformational family of 2',3'-didehydro-2',3'-dideoxyguanosine: quantum chemical and electron density topological study].
Comprehensive conformational analysis of the biologically active nucleoside 2',3'-didehydro-2',3'-dideoxyaguanosine (d4G) has been performed at the MP2/6-311++G(d,p)//DFT B3LYP/6-31G(d,p) level of theory. The energetic, geometrical and polar characteristics of twenty d4G conformers as well as their conformational equilibrium were investigated. The electron density topological analysis allowed us to establish that the d4G molecule is stabilized by nine types of intramolecular interactions: O5'H...N3, O5'H...C8, C8H...O5', C2'H...N3, C5'H1...N3, C5'H2...N3, C8H...H1C5', C8H...H2'C5' and N2H1...O5'. The obtained results of conformational analysis permit us to think that d4G may be a terminator of the DNA chain synthesis in the 5'-3' direction. Thus it can be inferred that d4G competes with canonical 2'-deoxyaguanosine in binding an active site of the corresponding enzyme.
A G
AG
Ponomar'ova
Ie P
IeP
Iurenko
R O
RO
Zhurakovs'kyĭ
D M
DM
Govorun
D020134:Catalytic Domain; D019295:Computational Biology; D004247:DNA / Q000737:chemistry* / Q000378:metabolism; D015224:Dideoxynucleosides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D004583:Electrons; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D018716:Molecular Mimicry; D011485:Protein Binding; D011789:Quantum Theory; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D013816:Thermodynamics
D015224:Dideoxynucleosides; D018894:Reverse Transcriptase Inhibitors; C057503:carbovir; D004247:DNA; D054303:HIV Reverse Transcriptase