Metabolomics is the systematic study of metabolites in biological fluids, cells or tissues. It reveals essential information about metabolism and disease. Metabolites have functional roles in a myriad of biological processes, as substrates and products of enzymatic reactions, but also as cofactors and regulators of a large number of biochemical mechanisms. These functions involve interactions between metabolites and macromolecules. However, methods to systematically study these interactions are still rare to date, in particular for the study of low affinity interactions.

The team from the RMN site in Paris, in collaboration with the CIRMMP (University of Florence) and the manufacturer Bruker, have developed a method for studying the weak interactions between metabolites and macromolecules in biological fluids. This new approach is based on high-resolution NMR relaxometry and does not require any invasive procedures or separation steps. High-resolution relaxometry consists of measuring the magnetic relaxation of nuclei in the stray field of a high-field magnet. The sample is moved rapidly by a shuttle system, between the magnetic center of the magnet, and chosen positions of the leakage field. We thus obtain measurements of the relaxation which cover several orders of magnitude of magnetic field, while retaining high-resolution information obtained thanks to the detection at the heart of the high-field magnet. The teams from the ENS, from the CIRMMP of Bruker, have shown that it is thus possible to detect interactions between small and macromolecules in human blood serum and to quantify the size of the complex. This work paves the way for the study of interactions between metabolites (or other small molecules) and proteins in biological fluids for interactomics or pharmaceutical applications. These results are published in JACS

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