Sandbox Reserved 654: Difference between revisions
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Current anti-HIV drugs target viral proteins such as reverse transcriptase, protease, and integrase<ref>Garg, R. et al (1999) Chem. Rev. 99, 3525 [http://pubs.acs.org/doi/abs/10.1021/cr9703358]</ref>. However, the discovery that Tat transactivation requires Lys-50 acetylation for functional transcription of the viral genome reveals a whole new approach to interfering with virus production. Drugs that target viral proteins have proven inadequate in eradicating the virus because the fast rate of mutations in the target proteins lead to developed drug resistance. Targeting a host cell protein that is necessary for viral reproduction (such as the PCAF bromodomain) as opposed to a viral protein, has the potential to inhibit HIV production much more effectively by disrupting HIV gene expression. | Current anti-HIV drugs target viral proteins such as reverse transcriptase, protease, and integrase<ref>Garg, R. et al (1999) Chem. Rev. 99, 3525 [http://pubs.acs.org/doi/abs/10.1021/cr9703358]</ref>. However, the discovery that Tat transactivation requires Lys-50 acetylation for functional transcription of the viral genome reveals a whole new approach to interfering with virus production. Drugs that target viral proteins have proven inadequate in eradicating the virus because the fast rate of mutations in the target proteins lead to developed drug resistance. Targeting a host cell protein that is necessary for viral reproduction (such as the PCAF bromodomain) as opposed to a viral protein, has the potential to inhibit HIV production much more effectively by disrupting HIV gene expression. | ||
Given the high selectivity of the bromodomain for its target protein, small ligand molecules are currently being designed and engineered to block Tat/PCAF association<ref>Zeng, L. (2005) J. Am. Chem. Soc. 127, 2376 [http://www.ncbi.nlm.nih.gov/pubmed/15724976]</ref>. In addition, new functions of the bromodomain remain to be discovered with implications for many human diseases such as cancer and Alzheimer's disease, and well as breakthroughs in our knowledge of transcription and gene regulation. | Given the high selectivity of the bromodomain for its target protein, <scene name='Sandbox_Reserved_654/Ligand/1'>small ligand molecules</scene> are currently being designed and engineered to block Tat/PCAF association<ref>Zeng, L. (2005) J. Am. Chem. Soc. 127, 2376 [http://www.ncbi.nlm.nih.gov/pubmed/15724976]</ref>. In addition, new functions of the bromodomain remain to be discovered with implications for many human diseases such as cancer and Alzheimer's disease, and well as breakthroughs in our knowledge of transcription and gene regulation. | ||
== '''References''' == | == '''References''' == | ||
<references/> | <references/> | ||
