Spectroscopic study and G-quadruplex DNA binding affinity of two bioactive papaverine-derived ligands

The interactions of G-quadruplex DNA with two oxidation products of papaverine, 6a,12a-diazadibenzo-a,g]fluorenylium derivative (1) and 2,3,9,10-tetramethoxy-12-oxo-12H-indolo2,1-a]isoquinolinium cation (2) were investigated. Their activity against telomerase was assessed using the conventional telomeric repeat amplification protocol (TRAP) assay. Effect of TRAP buffer and oligonucleotide length on the DNA-binding affinity of 1 and 2 were also studied. Three quadruplex-forming oligonucleotides with human telomeric sequence: dG₃(T₂AG₃)₃ (htel21), dAG₃(T₂AG₃)₃ (htel22), and d(T₂AG₃)₄ (htel24) were used in these investigations. Both ligands were capable of interacting with G4 DNA with binding stoichiometry indicating that two ligand molecules bind to G-quadruplex, which agrees with the binding model of end-stacking on terminal G-tetrads. Circular dichroism spectra revealed that preferences of quadruplex-forming oligonucleotide to adopt a particular topological structure may be also affected by the external ligand that binds to quadruplex. Telomerase activity was suppressed at very low ligand 1 and ligand 2 concentrations with an appreciable selectivity comparing with inhibition of Taq polymerase.