Thiazole orange-carboplatin triplex-forming oligonucleotide (TFO) combination probes enhance targeted DNA crosslinking
Hennessy J., Klimkowski P., Singleton D., Gibney A., Coche M., Farrell NP., El-Sagheer AH., Brown T., Kellett A.
We report a new class of carboplatin-TFO hybrid that incorporates a bifunctional alkyne-amine nucleobase monomer called AP-C3-dT that enables dual ‘click’ platinum(ii) drug conjugation and thiazole orange fluorophore coupling. Thiazole orange enhances the binding of Pt(ii)-TFO hybrids and provides an intrinsic method for monitoring triplex formation. These hybrid constructs possess increased stabilisation and crosslinking properties in comparison to earlier Pt(ii)-TFOs, and demonstrate sequence-specific binding at neutral pH.