Dimerization inhibitors of HIV-1 reverse transcriptase, protease and integrase: a single mode of inhibition for the three HIV enzymes?
The genome of human immunodeficiency virus type 1 (HIV-1) encodes 15 distinct proteins, three of which provide essential enzymatic functions: a reverse transcriptase (RT), an integrase (IN), and a protease (PR). Since these enzymes are all homodimers, pseudohomodimers or multimers, disruption of protein-protein interactions in these retroviral enzymes may constitute an alternative way to achieve HIV-1 inhibition. A growing number of dimerization inhibitors for these enzymes is being reported. This mini review summarizes some approaches that have been followed for the development of compounds that inhibit those three enzymes by interfering with the dimerization interfaces between the enzyme subunits.
Camarasa
María-José
MJ
Instituto de Química Médica (C.S.I.C.), Juan de la Cierva 3, 28006 Madrid, Spain. mj.camarasa@iqm.csic.es
Velázquez
Sonsoles
S
San-Félix
Ana
A
Pérez-Pérez
María-Jesús
MJ
Gago
Federico
F
D019380:Anti-HIV Agents / Q000494:pharmacology*; D019281:Dimerization; D015195:Drug Design; D019427:HIV Integrase / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D016333:HIV Protease / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology; D006801:Humans; D008958:Models, Molecular; D018894:Reverse Transcriptase Inhibitors / Q000494:pharmacology
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D019427:HIV Integrase; D054303:HIV Reverse Transcriptase; D016333:HIV Protease