Sequences in the HSP90 promoter form G-quadruplex structures with selectivity for disubstituted phenyl bis-oxazole derivatives
Author
Ohnmacht, Stephan A.
Micco, Marialuisa
Petrucci, Vanessa
Todd, Alan K.
Reszka, Anthony P.
Gunaratnam, Mekala
Carvalho, Marta A.
Zloh, Mire
Neidle, Stephen
Attention
2299/12472
Abstract
The HSP90 protein is an important target in cancer. We report here that stable quadruplex DNAs can be formed from a promoter sequence in the HSP90 gene, on the basis of melting, circular and NMR studies, and show that these can be selectively targeted by non-macrocyclic quadruplex-stabilizing phenyl bis-oxazole derivatives. These do not bind significantly to duplex DNA and show low stabilization of the human telomeric quadruplex. These results suggest an approach to targeting HSP90 at the DNA level.