title: Spectroscopic study and G-quadruplex DNA binding affinity of two bioactive papaverine-derived ligands.
abstract: 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-indolo[2,1-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: dG(3)(T(2)AG(3))(3) (htel21), dAG(3)(T(2)AG(3))(3) (htel22), and d(T(2)AG(3))(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.
authors: Faculty of Chemistry, A. Mickiewicz University, 60-780 Poznan, Poland.
authors: Elzbieta
authors: E
authors: Galezowska
authors: Anna
authors: A
authors: Masternak
authors: Blazej
authors: B
authors: Rubis
authors: Artur
authors: A
authors: Czyrski
authors: Maria
authors: M
authors: Rybczyńska
authors: Tadeusz W
authors: TW
authors: Hermann
authors: Bernard
authors: B
authors: Juskowiak
mesh_terms: D001665:Binding Sites; D004247:DNA / Q000737:chemistry*; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D010208:Papaverine / Q000031:analogs & derivatives* / Q000737:chemistry*; D013056:Spectrophotometry, Ultraviolet
chemical_list: D008024:Ligands; D004247:DNA; D010208:Papaverine