Recognition and Stabilization of Quadruplex DNA by a Potent New Telomerase Inhibitor: NMR Studies of the 2:1 Complex of a Pentacyclic Methylacridinium Cation with d(TTAGGGT)4

Abstract

Guided by 24 drug–DNA NOEs, the complex formed between RHPS4 (a novel fluorinated polycyclic methylacridinium salt with potent telomerase activity) and d(TTAGGGT)4 has been modeled by using MD simulations with drug molecules intercalated at the ApG and GpT steps. A low-energy structure for the 2:1 complex has a partial positive charge on the acridine 13-N atom (which acts as a pseudo potassium ion) positioned above the center of the G-tetrad (see picture).