An octahedral cobalt(III) complex with axial NH3 ligands that templates and selectively stabilises G-quadruplex DNA
File(s)Supporting Information-Revised-Final.pdf (3.26 MB) Vilar-ChemEurJ-2019-Co-G4-DNA-Accepted.pdf (1.68 MB)
Supporting information
Accepted version
Author(s)
Vilar, Ramon
Ruehl, Carmen L
Lim, Aaron HM
Kench, Timothy
Mann, David J
Type
Journal Article
Abstract
Guanine-rich sequences of DNA are known to readily fold into tetra-stranded helical structures known as G-quadruplexes (G4). Due to their biological relevance, G4s are potential anticancer drug targets and therefore there is significant interest in molecules with high affinity for these structures. Most G4 binders are polyaromatic planar compounds which π-π stack on the G4's guanine tetrad. However, many of these compounds are not very selective since they can also intercalate into duplex DNA. Herein we report a new class of binder based on an octahedral cobalt(III) complex that binds to G4 via a different mode involving hydrogen-bonding, electrostatic interactions and π-π stacking. We show that this new compound binds selectivity to G4 over duplex DNA (particularly to the G-rich sequence of the c-myc promoter). This new octahedral complex also has the ability to template he formation of G4 DNA from the unfolded sequence. Finally, we show that upon binding to G4, the complex prevents helicase Pif1-p from unfolding the c-myc G4 structure.
Date Issued
2019-07-22
Date Acceptance
2019-05-09
Citation
Chemistry - A European Journal, 2019, 25 (41), pp.9691-9700
ISSN
0947-6539
Publisher
Wiley
Start Page
9691
End Page
9700
Journal / Book Title
Chemistry - A European Journal
Volume
25
Issue
41
Copyright Statement
© 2019 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim. This is the accepted version of the following article: C. L. Ruehl, A. H. M. Lim, T. Kench, D. J. Mann, R. Vilar, Chem. Eur. J. 2019, 25, 9691, which has been published in final form at https://doi.org/10.1002/chem.201901569
Identifier
https://www.ncbi.nlm.nih.gov/pubmed/31087710
Subjects
Cobalt complexes
DNA
DNA binding
G-quadruplexes
Helicase
Publication Status
Published
Coverage Spatial
Germany
Date Publish Online
2019-05-14