AZT binds RNA at multiple sites.

摘要: Azidothymidine (AZT) is a widely used inhibitor of type I human immunodeficiency virus (HIV) reverse transcriptase that act as DNA chain terminator. Studies have shown primer unblocking and rescue synthesis AZT-resistant HIV-1 on RNA templates. Our recent study showed AZT bindings to the G-C, A-T base pairs backbone phosphate group duplex resulting in partial conformational changes. This was designed examine interaction with aqueous solution at physiological condition, using different drug/RNA (phosphate) molar ratios 1/800 1/2 constant concentration 1.25 or 12.5 mM (phosphate). Capillary electrophoresis, FTIR, UV-visible difference spectroscopic methods molecular modeling were determine drug binding sites, constants, effects complexation conformation. Structural analysis binds through G-C A-U bases two constants K1=7.3 x 10(5) M(-1) K2=1.90 M(-1). The distributions 54% 36% A-U, 10% group. remains A-family structure sugar pucker C2'-endo/anti conformation AZT-RNA complexes. Molecular studies show hydrogen bondings between donor groups.