Spectroscopic study of binding of a cationic Pheophorbide-a to an antiparallel quadruplex Tel22

Abstract

To study the binding of a water-soluble cationic Pheophorbide-a derivative (CatPheo-a) ta a Na +-stabilized antiparallel quadruplex formed by 22-mer oligonucleotide d[AG3(T 2 AG 3) 3 ] of the human DNA telomeric sequence (Tel22, PDB ID: 143D). Methods. Absorption and polarized fluorescence spectroscopy were used to determine the properties of DNA-ligand complexes. Fluorescence titration was applied to evaluate the Tel22 dye binding affinity. Absorption melting was used to estimate the effect of CatPheo-a on thermodynamic parameters of the Tel22 quadruplex folding. IR spectroscopy was used to detect singlet oxygen generation. Results. CatPheo-a was found to bind effectively to the Tel22 quadruplex via two competitive binding modes, which are characterized by opposite changes in the dye fluorescence. The spectroscopic properties of CatPheo-a + Tel22 complexes were determined. Thermodynamic parameters of the Tel22 quadruplex folding with/without CatPheo-a were calculated. Conclusions. CatPheo-a destabilizes the quadruplex structure of Tel22 with a twofold decrease in the equilibrium quadruplex folding constant at 37°C. The efficiency of singlet oxygen generation by CatPheo-a is higher than that by the anionic Pheo-a.