A possible improvement for structure-based drug design illustrated by the discovery of a Tat HIV-1 inhibitor.
The HIV-1 Tat protein is a promising target for AIDS therapy, due to its extra-cellular roles against the immune system. From the 2D-NMR structure of Tat, we have designed molecules, called TDS, able to bind to Tat and inhibit HIV-1 replication in vitro. This new family of antivirals is composed of a triphenylene aromatic ring substituted with at least one carbon chain bearing a succinimide group. These ligands are prepared from triphenylene or 2,6,10-trimethylphenylene in 3-6 steps depending on the target molecule.
Laboratoire de Synthèse Organique, CNRS UMR 6513, Faculté des Sciences, 2 rue de la Houssinière, BP 92208, 44322 Nantes Cedex 3, France.
Mickaël
M
Montembault
Giang
G
Vo-Thanh
Abdallah
A
Deyine
Valérie
V
Fargeas
Monique
M
Villiéras
Ané
A
Adjou
Didier
D
Dubreuil
Didier
D
Esquieu
Catherine
C
Grégoire
Sandrine
S
Opi
Jean-Marie
JM
Péloponèse
Grant
G
Campbell
Jennifer
J
Watkins
Jean
J
de Mareuil
Anne-Marie
AM
Aubertin
Christian
C
Bailly
Erwann
E
Loret
Jacques
J
Lebreton
D019380:Anti-HIV Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D015696:Gene Products, tat / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D013329:Structure-Activity Relationship; D054322:tat Gene Products, Human Immunodeficiency Virus
D019380:Anti-HIV Agents; D015696:Gene Products, tat; D054322:tat Gene Products, Human Immunodeficiency Virus