Premium
NMR Structure of a Triangulenium‐Based Long‐Lived Fluorescence Probe Bound to a G‐Quadruplex
Author(s) -
Kotar Anita,
Wang Baifan,
Shivalingam Arun,
GonzalezGarcia Jorge,
Vilar Ramon,
Plavec Janez
Publication year - 2016
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201606877
Subject(s) - g quadruplex , chemistry , stacking , affinities , molecule , crystallography , binding affinities , fluorescence , guanine , ligand (biochemistry) , stereochemistry , stoichiometry , molecular dynamics , proton nmr , computational chemistry , dna , nucleotide , receptor , physics , biochemistry , organic chemistry , quantum mechanics , gene
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.