title: 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.affiliation: Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, PA 15261, USA. CremerN@msx.dept-med.pitt.edu
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sluis-Cremer
authors.forename: Gilda
authors.initials: G
authors.lastname: Tachedjian
mesh_terms: D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D019281:Dimerization; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology; D019427:HIV Integrase / Q000737:chemistry / Q000187:drug effects; D016333:HIV Protease / Q000737:chemistry / Q000187:drug effects; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors / Q000737:chemistry; D015497:HIV-1 / Q000201:enzymology*; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry* / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D010455:Peptides; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D016333:HIV Protease