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Article Dans Une Revue Analytical Chemistry Année : 2023

Solution and Gas-Phase Stability of DNA Junctions from Temperature-Controlled Electrospray Ionization and Surface-Induced Dissociation

Résumé

DNA three-way junction (TWJ) structures transiently form during key cellular processes such as transcription, replication, and DNA repair. Despite their significance, the thermodynamics of TWJs, including the influence of strand length, base pair composition, and ligand binding on TWJ stability and dissociation mechanisms, are poorly understood. To address these questions, we interfaced temperaturecontrolled nanoelectrospray ionization mass spectrometry (TC-nESI-MS) with a cyclic ion mobility spectrometry (cIMS) instrument that was also equipped with a surface-induced dissociation (SID) stage. This novel combination allowed us to investigate the structural intermediates of three TWJ complexes and examine the effects of GC base pairs on their dissociation pathways. We found that two TWJ-specific ligands, 2,7-tris-naphthalene (2,7-TrisNP) and tris-phenoxybenzene (TrisPOB), lead to TWJ stabilization, revealed by an increase in the melting temperature (T m) by 13 or 26 °C, respectively. To gain insights into conformational changes in the gas phase, we employed cIMS and SID to analyze TWJs and their complexes with ligands. Analysis of IM arrival distributions suggested a single-step dissociation of TWJs and their intermediates for the three studied TWJ complexes. Upon ligand binding, a higher SID energy by 3 V (2,7-TrisNP) and 5 V (TrisPOB) was required to induce 50% dissociation of TWJ, compared to 38 V in the absence of ligands. Our results demonstrate the power of utilizing TC-nESI-MS in combination with cIMS and SID for thermodynamic characterization of TWJ complexes and investigation of ligand binding. These techniques are essential for the TWJ design and development as drug targets, aptamers, and structural units for functional biomaterials.
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Dates et versions

hal-04238369 , version 1 (13-10-2023)

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Adam Pruška, Julian A Harrison, Anton Granzhan, Adrien Marchand, Renato Zenobi. Solution and Gas-Phase Stability of DNA Junctions from Temperature-Controlled Electrospray Ionization and Surface-Induced Dissociation. Analytical Chemistry, 2023, 95 (38), pp.14384-14391. ⟨10.1021/acs.analchem.3c02742⟩. ⟨hal-04238369⟩
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