Analysis of Interactions between Telomeric i‐Motif DNA and a Cyclic Tetraoxazole Compound

Abstract

The interaction of a macrocyclic tetraoxazole compound, L2H2-4OTD (1), with two aminoalkyl side chains and telomeric i-motif, was investigated by means of electrophoretic mobility shift assay, circular dichroism spectroscopy, mass spectrometry and NMR spectroscopy analyses. The results indicate that 1 interacts with the i-motif structure at two preferred binding sites.

Mechanical unfolding of ensemble biomolecular structures by shear force

“…Single-molecule mechanical unfolding of the same i-motif in presence of the L2H2-4OTD generated a similar K d (31 µM) in optical tweezers (Figure S7). This K d is also comparable to that measured by gel shift (105 µM) 13 . These results validated the accuracy of our shear flow based mechanical unfolding approach.…”

“…These shear rates are equivalent to 17-50 pN mechanical force after comparison with mechanical unfolding of the same DNA structure in optical tweezers. In the presence of an i-motif ligand, L2H2-4OTD 13 , less unfolding was observed for i-motif under the same shear force, consistent with increased mechanical stability of the L2H2-4OTD bound i-motif. Such a strategy allowed us to reveal a dissociation constant of 36 µM for the L2H2-4OTD binding to the i-motif, a value consistent with that obtained by single-molecule mechanical unfolding in optical tweezers (31 µM) and close to that measured by gel shift.…”

“…13 L2H2-4OTD is a compound that can bind to i-motif structures with a dissociation constant (K d ) in micromolar range. 13 After the above-mentioned Cy5 and Iowa Black® RQ labelled i-motif (Oligo 5, Table S2) was mixed with the L2H2-4OTD at different concentrations (6-60 µM) in the same buffer, the mixture was subjected to the shear force generated in the homogenizer (Figure 2). We anticipated more Cy5 fluorescence would be Please do not adjust margins Please do not adjust margins quenched by Iowa Black® RQ at a particular shear rate since the unfolding of the i-motif became more difficult upon the ligand binding 17 .…”

Académie des Sciences Prizes 2018

“…Lesage konzentriert sich auf die Entwicklung von Festkçrper-NMR-Spektroskopie mit Rotation im magischen Winkel und Verstärkung durch dynamische Kernpolarisation (DNP);z u diesem Thema hatte sie vor kurzem einen Beitrag in der Angewandten Chemie. [5] CØline Merlet (Centre Inter-universitaire de Recherche et dIngØnierie des MatØriaux (CIRI-MAT) und UniversitØ Paul Sabatier,T oulouse) erhält den "Prix Louis Armand". [3b] Julien Nicolas (Institut Galien Paris-Sud) wird mit dem "Prix Novocap de lAcadØmie des Sciences" ausgezeichnet.…”

“…Sie beschrieb in ChemPhysChem die Bildung von RNA-"Kissing"-Komplexen, und sie war Koautorin eines ChemBioChem-Beitrags über Wechselwirkungen zwischen einem makrocyclischen Te traoxazol und i-Motiven in telomerer DNA. [5] CØline Merlet (Centre Inter-universitaire de Recherche et dIngØnierie des MatØriaux (CIRI-MAT) und UniversitØ Paul Sabatier,T oulouse) erhält den "Prix Louis Armand". Merlet studierte an der École Nationale SupØrieure de Chimie de Paris und der UMPC und promovierte 2013 unter Anleitung von Mathieu Salanne und Benjamin Rotenberg an der UMPC.V on 2013 bis 2017 war sie als Postdoktorandin bei Clare Grey und Daan Frenkel an der University of Cambridge,und 2017 wurde sie als CNRS-Forscherin am CIRIMATangestellt.…”