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NMR Structure of a Triangulenium‐Based Long‐Lived Fluorescence Probe Bound to a G‐Quadruplex |
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| Authors: | Anita Kotar Dr Baifan Wang Dr Arun Shivalingam Dr Jorge Gonzalez‐Garcia Prof?Dr Ramon Vilar Prof?Dr Janez Plavec |
| Institution: | 1. Slovenian NMR Center, National Institute of Chemistry, Ljubljana, Slovenia;2. Department of Chemistry, Imperial College London, London, UK;3. EN-FIST Center of Excellence, Ljubljana, Slovenia;4. Faculty of Chemistry and Chemical Technology, University of Ljubljana, Ljubljana, Slovenia |
| Abstract: | An NMR structural study of the interaction between a small‐molecule optical probe (DAOTA‐M2) and a G‐quadruplex from the promoter region of the c‐myc oncogene revealed that they interact at 1:2 binding stoichiometry. NMR‐restrained structural calculations show that binding of DAOTA‐M2 occurs mainly through π–π stacking between the polyaromatic core of the ligand and guanine residues of the outer G‐quartets. Interestingly, the binding affinities of DAOTA‐M2 differ by a factor of two for the outer G‐quartets of the unimolecular parallel G‐quadruplex under study. Unrestrained MD calculations indicate that DAOTA‐M2 displays significant dynamic behavior when stacked on a G‐quartet plane. These studies provide molecular guidelines for the design of triangulenium derivatives that can be used as optical probes for G‐quadruplexes. |
| Keywords: | G-quadruplexes molecular dynamics NMR spectroscopy optical probes structure elucidation |