摘要 : An extensive conformational analysis of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine, d4T), a nucleoside reverse transcriptase inhibitor widely used in anti-retroviral therapy, is presented. At 298.15 K all 19 allowed d4T con... 展开 An extensive conformational analysis of 2',3'-didehydro-2',3'-dideoxythymidine (stavudine, d4T), a nucleoside reverse transcriptase inhibitor widely used in anti-retroviral therapy, is presented. At 298.15 K all 19 allowed d4T conformers are within the 5.51 kcal/mol Gibbs free energy range. Eight types of specific intramolecular interactions, which govern the conformational properties of d4T, were identified, namely: O5?H...O2, C1?H...O2, C6H...O5?, C6H...O4?, C5?H1...O2, C5?H2...O2, C6H...H1C5? and C2?...O2. The results confirm the current point of view that the biological activity of d4T is, most likely, connected with termination of the DNA chain synthesis in the 5'-3' direction. Thus, d4T competes with canonical thymidine for binding to the HIV-1 reverse transcriptase active site 收起