Enhanced sensitivity of rapidly exchanging amide protons by improved phase cycling and the constructive use of radiation damping

Two alternative, general methods are presented that lead to enhanced signal intensity of rapidly exchanging protons. Both methods work by avoiding saturation of the water resonance, and are convenient to implement since they do not use any selective pulses. One method carefully chooses proton pulse phases and gradient strength and position in such a way that the water is realigned along the +z axis at the beginning of the acquisition time. An alternative method is proposed for cases where the pulse sequence does not allow such phase cycling. The latter uses radiation damping to bring water back to the +z axis 20-30 ms after acquisition. The methods are applied to the triple-resonance experiments HNCA, HNCO and HN(CO)CA. Both methods require pulsed B₀ field gradients and can result in higher signal intensity by a factor of two or more.