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Quadruplex DNA‐Stabilising Dinuclear Platinum(II) Terpyridine Complexes with Flexible Linkers
Authors:Dale L Ang  Dr Benjamin W J Harper  Dr Leticia Cubo  Dr Oscar Mendoza  Prof Ramon Vilar  Prof Janice Aldrich‐Wright
Institution:1. Nanoscale Organisation and Dynamics Group, School of Science and Health, Western Sydney University, Penrith, Australia;2. Department of Chemistry, Imperial College London, London, UK;3. Institute of Chemical Biology, Imperial College London, London, UK
Abstract:Four dinuclear terpyridineplatinum(II) (Pt–terpy) complexes were investigated for interactions with G‐quadruplex DNA (QDNA) and duplex DNA (dsDNA) by synchrotron radiation circular dichroism (SRCD), fluorescent intercalator displacement (FID) assays and fluorescence resonance energy transfer (FRET) melting studies. Additionally, computational docking studies were undertaken to provide insight into potential binding modes for these complexes. The complexes demonstrated the ability to increase the melting temperature of various QDNA motifs by up to 17 °C and maintain this in up to a 600‐fold excess of dsDNA. This study demonstrates that dinuclear Pt–terpy complexes stabilise QDNA and have a high degree of selectivity for QDNA over dsDNA.
Keywords:circular dichroism  DNA  FRET  G-quadruplexes  platinum
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