Dimerization of human immunodeficiency virus type 1 reverse transcriptase. A target for chemotherapeutic intervention

Abstract

Recombinant human immunodeficiency virus type 1 reverse transcriptase has been used to investigate the process of dimer formation and the properties of the different mono- and dimeric forms of the enzyme. The studies show that reverse transcriptase activity is exclusively confined to the dimeric forms. As we also demonstrate, the association rate constant between the monomers is relatively low so that the dimer-monomer equilibrium is very slowly established. This offers a new and potentially interesting target for antiviral chemotherapy with presumably higher specificity than the currently used nucleoside analogs (Yarchoan, R., Mitsuya, H., Myers, C.E., and Broder, S. (1989) N. Eng. J. Med. 321, 726-738), which in their active triphosphorylated form are also inhibitors of cellular polymerases.