2018
DOI: 10.1021/jacs.8b07302
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Thermal Denaturation of DNA G-Quadruplexes and Their Complexes with Ligands: Thermodynamic Analysis of the Multiple States Revealed by Mass Spectrometry

Abstract: Designing ligands targeting G-quadruplex nucleic acid structures and affecting cellular processes is complicated because there are multiple target sequences and some are polymorphic. Further, structure alone does not reveal the driving forces for ligand binding. To know why a ligand binds, the thermodynamics of binding must be characterized. Electrospray mass spectrometry enables one to detect and quantify each specific stoichiometry (number of strands, cations, and ligands) and thus to simultaneously determin… Show more

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Cited by 84 publications
(92 citation statements)
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“…10 In addition, in combination with a temperature-controlled ionization source, native MS has been applied to identify protein unfolding intermediates, 11 and to investigate the thermodynamic properties of ligands binding to DNA structures. 12…”
Section: Introductionmentioning
confidence: 99%
“…10 In addition, in combination with a temperature-controlled ionization source, native MS has been applied to identify protein unfolding intermediates, 11 and to investigate the thermodynamic properties of ligands binding to DNA structures. 12…”
Section: Introductionmentioning
confidence: 99%
“…The binding ratio is commonly obtained through binding kinetic measurements, such as surface plasmon resonance (SPR) and UV/Vis spectroscopy . Previously a 2:1 ligand/quadruplex complex (MK2L2) has been reported by ESI‐MS . ITC, adopted herein, can also provide information on the possible binding stoichiometry of ligand and G‐quadruplex.…”
Section: Methodsmentioning
confidence: 99%
“…MS melting experiments were conducted by using a TCnESI source coupled to the q-TOF mass spectrometer. The details about construction and performance of the TCnESI source are described by Marchand et al 26 Briefly, the capillary emitter is embedded between two copper blocks, which are either heated or cooled by a Peltier element (Adaptive ET-127-10-13-RS, 15.7 V, 37.9 W) powered by a Kikusui PMX18-5A supply (Kikusui Electonics Corp., Japan) and remotely controlled by a LabView software (National Instruments, USA). The temperature of the copper block was monitored using a bolt-mounted thermistor sensor (5000 Ω, ON-950-44005, Omega, standard accuracy of 0.2°C from 0 to 70°C) connected to a Keithley 2701E multimeter (Equipements Scientifiques, Garchies, France) and analyzed with LabView software.…”
Section: Tcnesimentioning
confidence: 99%
“…A direct titration approach was used to determine the equilibrium dissociation constant (K d ) for each glycovariant. Subsequently, the complex's thermal stability was evaluated by employing a homebuilt temperature-control nanoelectrospray (TCnESI) 26 where free mAb dissociation was monitored as a function of temperature. Additionally, our results were validated by microscale thermophoresis (MST), SPR and a cell-based assay using engineered natural killer (NK) cells expressing the high variant (V176) of CD16a receptor.…”
Section: Introductionmentioning
confidence: 99%