NMR Structure of a Triangulenium based Long-lived Fluorescence Probe Bound to G-quadruplex
File(s)
Supporting information
Accepted version
Author(s)
Type
Journal Article
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 c-myc oncogene
demonstrates their interaction at 1:2 binding stoichiometry. NMR restrained structural
calculations show that binding of DAOTA-M2 occurs mainly through the 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 to the outer G-quartets of the
unimolecular parallel G-quadruplex under study differ by a factor of two. Unrestrained MD
calculations indicate that DAOTA-M2 displays significant dynamic behavior when stacked
on a G-quartet plane. These studies provide molecular guidelines for design of triangulenium
derivatives that can be used as optical probes of G-quadruplexes.
probe (DAOTA-M2) and a G-quadruplex from the promoter region of c-myc oncogene
demonstrates their interaction at 1:2 binding stoichiometry. NMR restrained structural
calculations show that binding of DAOTA-M2 occurs mainly through the 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 to the outer G-quartets of the
unimolecular parallel G-quadruplex under study differ by a factor of two. Unrestrained MD
calculations indicate that DAOTA-M2 displays significant dynamic behavior when stacked
on a G-quartet plane. These studies provide molecular guidelines for design of triangulenium
derivatives that can be used as optical probes of G-quadruplexes.
Date Issued
2016-08-31
Date Acceptance
2016-08-02
Citation
Angewandte Chemie - International Edition, 2016, 55 (40), pp.12508-12511
ISSN
1433-7851
Publisher
Wiley
Start Page
12508
End Page
12511
Journal / Book Title
Angewandte Chemie - International Edition
Volume
55
Issue
40
Copyright Statement
This is the peer reviewed version of the following article: A. Kotar, B. Wang, A. Shivalingam, J. Gonzalez-Garcia, R. Vilar, J. Plavec, Angew. Chem. Int. Ed. 2016, 55, 12508, which has been published in final form at https://dx.doi.org/10.1002/anie.201606877. This article may be used for non-commercial purposes in accordance With Wiley Terms and Conditions for self-archiving.
Sponsor
Engineering & Physical Science Research Council (EPSRC)
The Royal Society
Grant Number
EP/H005285/1
NF140726
Subjects
G-quadruplexes
NMR spectroscopy
molecular dynamics
optical probes
structure elucidation
Organic Chemistry
03 Chemical Sciences
Publication Status
Published