Under physiological conditions, studies of intrinsically disordered proteins (IDPs) by conventional NMR methods based on proton detection are severely limited by fast amide-proton exchange with water. C-13 detection has been proposed as a solution to the exchange problem, but is hampered by low sensitivity. We propose a new pulse sequence combining proton-nitrogen cross-polarization and carbonyl detection to record high-resolution, high-sensitivity NMR spectra of IDPs under physiological conditions. To demonstrate the efficacy of this approach, we recorded a high-quality N-CO correlation spectrum of alpha-synuclein in bacterial cells at 37 degrees C.