DEVELOPMENT OF TRANSITION-STATE MIMETIC HIV PROTEASE INHIBITORS

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A number of potentially useful approaches for the therapy of acquired immunodeficiency syndrome (AIDS) and its related diseases have emerged. The use of family of 2',3'-dideoxynucleotides, such as 3'-azido-2',3'-dideoxythymidine (AZT or zidovudine), 2',3'dideoxycytidine (ddC or zalcitabine), and 2',3'-dideoxyinosine (ddI or didanosine), which target the reverse transcriptase of human immunodeficiency virus type I (HIV-1), the causative agent of AIDS, is one such approach. HIV also codes a virus-specific aspartic protease which is essential for its replication. The HIV protease mediates crucial proteolytic processing of viral protein precursors at a late stage in the replication of the virus. Thus, HIV protease also represents a virus-specific target for the therapy of HIV infections.