Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5370574 | Biophysical Chemistry | 2017 | 9 Pages |
â¢C8-conjugates of pyrrolobenzodiazepines with benzofused rings modulate sequence-selective DNA binding.â¢The conjugates bind best to guanines flanked by A/T-rich sequences.â¢Bi- and tri-phasic melting curves show that 14-mer oligonucleotides can bind more than one ligand.
DNA footprinting and melting experiments have been used to examine the sequence-specific binding of C8-conjugates of pyrrolobenzodiazepines (PBDs) and benzofused rings including benzothiophene and benzofuran, which are attached using pyrrole- or imidazole-containing linkers. The conjugates modulate the covalent attachment points of the PBDs, so that they bind best to guanines flanked by A/T-rich sequences on either the 5â²- or 3â²-side. The linker affects the binding, and pyrrole produces larger changes than imidazole. Melting studies with 14-mer oligonucleotide duplexes confirm covalent attachment of the conjugates, which show a different selectivity to anthramycin and reveal that more than one ligand molecule can bind to each duplex.
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