ABSTRACT

The elucidation of the etiology of AIDS and the efficacy of 3'-azido-3'-deoxythymidine, proven to prolong survival and to reduce morbidity in patients with established AIDS, have prompted intensive research directed toward the development of antiretroviral therapy for HIV infection. In addition to the requirement for a 2',3'-dideoxy structure, structure-activity studies demonstrated the need for the presence of the 5'-OH group. In the steady state, the concentration of enzyme forms free to bind dNTP is low relative to total enzyme, allowing apparent saturation of the enzyme to occur at relatively low concentrations of dNTP. In the absence of the other three 2'-deoxynucleoside-5'-triphosphates, the time course for incorporation of TTP into a defined-sequence DNA-primed RNA template66 was biphasic.