Prix et distinctions
Angew.Chem.Int. Ed., 2016, 55, 9886-9889
Nuclear Magnetic Resonance has benefited tremendously from the steady increase of magnetic fields. Spectacular improvements in both sensitivity and resolution have allowed the investigation of molecular systems of rising complexity. At very high fields, this progress may be jeopardized by line broadening due to chemical exchange or relaxation by chemical shift anisotropy. Here, we introduce a two-field NMR spectrometer designed for both excitation and observation of nuclear spins at two distinct magnetic fields in a single experiment. NMR spectra were obtained, with two dimensions acquired at vastly different magnetic fields. We show that signals of exchanging groups broadened beyond recognition at high field can be sharpened up to narrow peaks in a low-field dimension. Two-field NMR makes it possible to measure chemical shifts at optimal fields, allows the observation of molecular systems that suffer from internal dynamics, and opens new avenues for NMR at very high magnetic fields.
ChemBioChem 2016, 17, 1-5
An organometallic derivative of praziquantel was studied directly in worms by using inductively coupled plasma-mass spectrometry (ICP-MS) for quantification and synchrotronbased imaging. X-ray fluorescence (XRF) and IR absorption spectromicroscopy were used for the first time in combination to directly locate this organometallic drug candidate in schistosomes. The detection of both CO (IR) and Cr (XRF) signatures proved that the Cr(CO)3 core remained intact in the worms. Images showed a preferential accumulation at the worm’s tegument, consistent with a possible targeting of the calcium channel but not excluding other biological targets inside the worm.
Phys. Chem. Chem. Phys., 2016,18, 10144-10151
By monitoring the effect of deuterium decoupling on the decay of transverse 15N magnetization in D–15N spin pairs during multiple-refocusing echo sequences, we have determined fast D–D exchange rates kD and compared them with fast H–H exchange rates kH in tryptophan to determine the kinetic isotope effect as a function of pH and temperature.
Scientific Reports, 2016 Feb 3 ; 6:20237
Confocal laser scanning microscopy (CLSM) is the most popular technique for mapping the subcellular distribution of a fluorescent molecule and is widely used to investigate the penetration properties of exogenous macromolecules, such as cell-penetrating peptides (CPPs), within cells. Despite the membrane-association propensity of all these CPPs, the signal of the fluorescently labeled CPPs did not colocalize with the plasma membrane. We studied the origin of this fluorescence extinction and the overall consequence on the interpretation of intracellular localizations from CLSM pictures. We demonstrated that this discrepancy originated from fluorescence self-quenching. The fluorescence was unveiled by a “dilution” protocol, i.e. by varying the ratio fluorescent/non-fluorescent CPP. This strategy allowed us to rank with confidence the subcellular distribution of several CPPs, contributing to the elucidation of the penetration mechanism. More generally, this study proposes a broadly applicable and reliable method to study the subcellular distribution of any fluorescently labeled molecules.