Modulation of the oligomeric structures of HIV-1 retroviral enzymes by synthetic peptides and small molecules.

Abstract

The efficacy of antiretroviral agents approved for the treatment of HIV-1 infection is limited by the virus's ability to develop resistance. As such there is an urgent need for new ways of thinking about anti-HIV drug development, and accordingly novel viral and cellular targets critical to HIV-1 replication need to be explored and exploited. The retroviral RNA genome encodes for three enzymes essential for viral replication: HIV-1 protease (PR), HIV-1 reverse transcriptase (RT) and HIV-1 integrase (IN). The enzymatic functioning of each of these enzymes is entirely dependent on their oligomeric structures, suggesting that inhibition of subunit-subunit assembly or modulation of their quaternary structures provide alternative targets for HIV-1 inhibition. This review discusses the recent advances in the design and/or identification of synthetic peptides and small molecules that specifically target the subunit-subunit interfaces of these retroviral enzymes, resulting in the inactivation of their enzymatic functioning.

• Authors: Nicolas Sluis-Cremer, Gilda Tachedjian
• Journal: European journal of biochemistry (Eur J Biochem) Vol. 269 Issue 21 Pg. 5103-11 (Nov 2002) ISSN: 0014-2956 [Print] England
• PMID: 12392542 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Review)

Chemical References

• Anti-HIV Agents
• Enzyme Inhibitors
• Peptides
• HIV Integrase
• HIV Reverse Transcriptase
• HIV Protease

Topics

• Anti-HIV Agents (chemistry, pharmacology)
• Dimerization
• Drug Design
• Enzyme Inhibitors (chemistry, pharmacology)
• HIV Integrase (chemistry, drug effects)
• HIV Protease (chemistry, drug effects)
• HIV Reverse Transcriptase (antagonists & inhibitors, chemistry)
• HIV-1 (enzymology)
• Models, Molecular
• Peptides (chemistry, pharmacology)
• Protein Conformation (drug effects)