@article{Perrone2013, abstract = {G-quadruplexes, non-canonical nucleic acid structures, act as silencers in the promoter regions of human genes; putative G-quadruplex forming sequences are also present in promoters of other mammals, yeasts and prokaryotes. Here we show that also the HIV-1 LTR promoter exploits G-quadruplex-mediated transcriptional regulation with striking similarities to eukaryotic promoters and that treatment with a G-quadruplex ligand inhibits HIV-1 infectivity. Computational analysis on 953 HIV-1 strains substantiated a highly conserved G-rich sequence corresponding to Sp1 and NF-κB binding sites. Biophysical/biochemical analysis proved that two mutually exclusive parallel-like intramolecular G-quadruplexes, stabilized by small molecule ligands, primarily fold in this region. Mutations disrupting G-quadruplex formation enhanced HIV promoter activity in cells, whereas treatment with a G-quadruplex ligand impaired promoter activity and displayed antiviral effects. These findings disclose the possibility of inhibiting the HIV-1 LTR promoter by G-quadruplex-interacting small molecules, providing a new pathway to development of anti-HIV-1 drugs with unprecedented mechanism of action.}, author = {Perrone, Rosalba and Nadai, Matteo and Frasson, Ilaria and Poe, Jerrod A. and Butovskaya, Elena and Smithgall, Thomas E. and Palumbo, Manlio and Palù, Giorgio and Richter, Sara N.}, doi = {10.1021/jm400914r}, journal = {Journal of Medicinal Chemistry}, month = {aug}, pages = {6521-6530}, title = {A dynamic G-quadruplex region regulates the HIV-1 long terminal repeat promoter}, url = {http://www.ncbi.nlm.nih.gov/pubmed/23865750}, volume = {56}, year = {2013} }