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Current Medicinal Chemistry


ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Inhibitors of HIV-1 Tat-Mediated Transactivation

Author(s): S. N. Richter and G. Palu

Volume 13 , Issue 11 , 2006

Page: [1305 - 1315] Pages: 11

DOI: 10.2174/092986706776872989

Price: $65


The transactivation responsive (TAR) RNA is the 5-leader sequence of the HIV-1 mRNA genome and interacts with the Tat protein during transcription. Tat and the positive transcription elongation factor (PTEFb) complex bind to TAR to promote efficient transcription of the full-length HIV genome. In the absence of the TAR█Tat█P-TEFb interaction, viral transcription is inefficient, which makes this RNA-protein complex an important target for therapeutic intervention of HIV replication. Inhibitors of HIV-1 transactivation mainly target: 1) TAR RNA, 2) Tat protein and 3) Tat█P-TEFb complex. 1) Compounds against TAR RNA are the most numerous: besides cationic peptides, which were initially developed, recent advances in TAR binding inhibitors include oligonucleotide based-agents and small molecules. Specific research efforts are currently underway to increase cellular uptake. 2) By targeting the Tat protein, both transactivation and other Tatmediated intra/extracellular functions are affected. Various biopolymeric drugs are reported to effectively inhibit Tat activity. In addition, Tat-targeted antibodies have recently been developed. 3) Intracellular proteins have been discovered to disrupt Tat█P-TEFb interaction, raising the chance of inhibiting HIV-1 transcription via novel mechanisms.

Keywords: HIV-1, Inhibitors, P-TEFb, TAR RNA, Tat, Transactivation

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