Targeting Guanine Quadruplexes with Luminescent Platinum(II) Complexes Bearing a Pendant Nucleobase.

Abstract

Guanine quadruplexes are tetra-stranded nucleic acid structures currently raising significant interest in the context of the development of potential anticancer therapeutics with a new mode of action. They are composed of planar guanine tetrads, allowing a high-affinity targeting by using molecules with a large π surface. However, the extreme topological versatility of guanine quadruplexes impedes a straightforward targeting of particular preselected guanine-rich sequences. We report here a systematic study of a family of luminescent platinum(II) complexes devised to overcome this challenge. By attaching a pendant adenine or thymine nucleobase as a substituent to one of the ligands at the platinum center, an additional recognition site is introduced with the aim of modulating the affinity of the metal complex to different DNA sequences. By comparing different attached nucleobases and a series of linker moieties, first conclusions are drawn with respect to the scope of this approach.