Probing ligand and cation binding sites in G-quadruplex nucleic acids by mass spectrometry and electron photodetachment dissociation sequencing

Mass spectrometry provides exquisite details on ligand and cation binding stoichiometries with a DNA target. The next important step is to develop reliable methods to determine the cation and ligand binding sites in each complex separated by using a mass spectrometer. To circumvent the caveat of lig...

Full description

Saved in:
Bibliographic Details
Published in:Analyst (London) 2019-06, Vol.144 (11), p.3518-3524
Main Authors: Paul, Dababrata, Marchand, Adrien, Verga, Daniela, Teulade-Fichou, Marie-Paule, Bombard, Sophie, Rosu, Frédéric, Gabelica, Valérie
Format: Article
Language:English
Subjects:
Analytical chemistry
Biochemistry
Biochemistry, Molecular Biology
Biological Physics
Biophysics
Chemical Physics
Chemical Sciences
Life Sciences
or physical chemistry
Physics
Structural Biology
Theoretical and
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Mass spectrometry provides exquisite details on ligand and cation binding stoichiometries with a DNA target. The next important step is to develop reliable methods to determine the cation and ligand binding sites in each complex separated by using a mass spectrometer. To circumvent the caveat of ligand derivatization for cross-linking, which may alter the ligand binding mode, we explored a tandem mass spectrometry (MS/MS) method that does not require ligand derivatization, and is therefore also applicable to localize metal cations. By putting more negative charge states on the complexes using supercharging agents, and by creating radical ions by electron photodetachment, oligonucleotide bonds become weaker than the DNA-cation or DNA-ligand noncovalent bonds upon collision-induced dissociation of the radicals. This electron photodetachment (EPD) method allows one to locate the binding regions of cations and ligands by top-down sequencing of the oligonucleotide target. The very potent G-quadruplex ligands 360A and PhenDC3 were found to replace a potassium cation and bind close to the central loop of 4-repeat human telomeric sequences. Tandem mass spectrometry: native top-down sequencing by electron photodetachment dissociation (EPD) reveals ligand binding sites on DNA G-quadruplexes.
ISSN:0003-2654
1364-5528
DOI:10.1039/c9an00398c