UMR 7203 : Structure et Dynamique des Biomolécules

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Transportable hyperpolarized metabolites

Nature Communications 8, Article number: 13975 (2017)

 

Nuclear spin hyperpolarization of 13C-labelled metabolites by dissolution dynamic nuclear polarization can enhance the NMR signals of metabolites by several orders of magnitude, which has enabled in vivo metabolic imaging by MRI. However, because of the short lifetime of the hyperpolarized magnetization (typically o1 min), the polarization process must be carried out close to the point of use. Here we introduce a concept that markedly extends hyperpolarization lifetimes and enables the transportation of hyperpolarized metabolites. The hyperpolarized sample can thus be removed from the polarizer and stored or transported for use at remote MRI or NMR sites. We show that hyperpolarization in alanine and glycine survives 16 h storage and transport, maintaining overall polarization enhancements of up to three orders of magnitude.

Investigation of Intrinsically Disordered Proteins through Exchange with Hyperpolarized Water

Angew. Chem. Int. Ed2017, 56, 389 –392

 

Hyperpolarized water can selectively enhance NMR signals of rapidly exchanging protons in osteopontin (OPN), a metastasis-associated intrinsically disordered protein (IDP), at near-physiological pH and temperature. The transfer of magnetization from hyperpolarized water is limited to solventexposed residues and therefore selectively enhances signals in 1H-15N correlation spectra. Binding to the polysaccharide heparin was found to induce the unfolding of preformed structural elements in OPN.

Dissolution dynamic nuclear polarization of deuterated molecules enhanced by cross-polarization

J. Chem. Phys., 2016, 145, 194203

 

We present novel means to hyperpolarize deuterium nuclei in 13CD2  groups at cryogenic temperatures. The method is based on cross-polarization from 1 H to 13 C and does not require any radio-frequency fields applied to the deuterium nuclei. After rapid dissolution, a new class of longlived spin states can be detected indirectly by 13C NMR in solution. These long-lived states result from a sextet-triplet imbalance (STI) that involves the two equivalent deuterons with spin I  = 1. An STI has similar properties as a triplet-singlet imbalance that can occur in systems with two equivalent I  = 1/2  spins. Although the lifetimes TSTI  are shorter than T1(Cz), they can exceed the life-time T1(Dz) of deuterium Zeeman magnetization by a factor of more than 20.

 

Recovering Invisible Signals by Two-Field Nuclear Magnetic Resonance Spectroscopy

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.

 

Kinetic isotope effects for fast deuterium and proton exchange rates

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.