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Detergent-soluble proteins (DSPs) are commonly dissolved in lipid buffers for NMR experiments, but the huge lipid proton signal prevents recording of high-quality spectra. The use of costly deuterated lipids is thus required to replace nondeuterated ones. With conventional methods, detergents like dodecylphosphocholine (DPC) cannot be fully exchanged due to their high binding affinity to hydrophobic proteins. We propose an original and simple protocol which combines the use of acetonitrile, dialysis and lyophilization to disrupt the bi