New platinum(II) complexes targeting the loops of the human telomeric G-quadruplex

Abstract

Two novel series of platinum(II) complexes have been designed and shown to interact with the human telomeric G-quadruplex-DNA via different binding modes: i- terpyridine-platinum (Pt-tpy) complexes covalently interact with quadruplex-DNA via selective platination of adenine residues of the loops, their interaction being driven by the aromatic surface of the ligand; ii- platinum-quinacridine hybrid (Pt-MPQ) interacts with quadruplex-DNA via a dual noncovalent/covalent binding mode, targeting preferentially guanines constitutive of external G-quartets. Therefore, platinum complexes presented herein constitute potential agents for irreversible trapping of G-quadruplex.DNA.