Authors:
M Nadai, F Doria, M Di Antonio, G Sattin, L Germani, C Percivalle, M Palumbo, SN Richter, M Freccero
Journal name: 
Biochimie
Citation info: 
93(8):1328-1340
Abstract: 
Selective recognition and alkylation of G-quadruplex oligonucleotides has been achieved by substituted naphathalene diimides (NDIs) conjugated to engineered phenol moieties by alkyl-amido spacers with tunable length and conformational mobility. FRET-melting assays, circular dichroism titrations and gel electrophoresis analysis have been carried out to evaluate both reversible stabilization and alkylation of the G-quadruplex. The NDIs conjugated to a quinone methide precursor (NDI-QMP) and a phenol moiety by the shortest alkyl-amido spacer exhibited a planar and fairly rigid geometry (modelled by DFT computation). They were the best irreversible and reversible G-quadruplex binders, respectively. The above NDI-QMP was able to alkylate the telomeric G-quadruplex DNA in the nanomolar range and resulted 100-1000 times more selective on G-quadruplex versus single- and double-stranded oligonucleotides. This compound was also the most cytotoxic against a lung carcinoma cell line.
DOI: 
http://doi.org/10.1016/j.biochi.2011.06.015
E-pub date: 
31 Aug 2011