title: [Energetic, conformational and electron density topological properties of 2',3'-didehydro-2',3'-dideoxythymidine: a quantum chemical study].
abstract: Comprehensive conformational analysis of 2',3'-didehydro-2',3'-dideoxythymidine (d4T), also known as anti-AIDS drug stavudine, has been performed for the first time at the MP2/6-311++G(d,p)//DFT B3LYP/6-31++G(d,p) level of the theory. It was established that d4T energy landscape contained 19 local minima, which corresponded to stable conformers. Eight types of specific intramolecular interactions, which govern the d4T conformational properties, were identified, namely: O5'H-O2, C1'H'-O2, C6H-O5', C6H-O4', C5'H1'-O2, C5'H2'-O2, C6H-H1'C5', C2'-O2. The obtained results confirm the actual point of view that d4T biological activity is, most likely, connected with termination of the DNA chain synthesis in the 5'-3' direction. Thus, d4T competes with canonical thymidine in binding an active site of HIV-1 reverse transcriptase.
authors.forename: A G
authors.initials: AG
authors.lastname: Ponomar'ova
authors.forename: Ie P
authors.initials: IeP
authors.lastname: Iurenko
authors.forename: R O
authors.initials: RO
authors.lastname: Zhurakivskiĭ
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D018360:Crystallography, X-Ray; D004279:DNA, Viral / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004583:Electrons; D006678:HIV / Q000187:drug effects / Q000502:physiology; D015658:HIV Infections / Q000188:drug therapy / Q000201:enzymology / Q000821:virology; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D008968:Molecular Conformation; D011789:Quantum Theory; D012984:Software; D013046:Specific Gravity; D018119:Stavudine / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D013816:Thermodynamics; D013936:Thymidine / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D019380:Anti-HIV Agents; D004279:DNA, Viral; D018119:Stavudine; C514824:reverse transcriptase, Human immunodeficiency virus 1; D054303:HIV Reverse Transcriptase; D013936:Thymidine