NMR studies of flexible peptides in cavities mimicking the synaptic cleft

Interaction of neuropeptides with postsynaptic receptors is characterized by a high entropic barrier originating from the combination of nanomolar concentration with low conformer population. The influence of high viscosity environments on conformer distribution can help overcoming this difficulty. In the attempt of simulating the physicochemical conditions of the synaptic cleft, 15N-labeled enkephalin has been studied in polyacrilamide gels swollen by different aqueous solutions in the temperature range 273-293 K. NOESY spectra in the gel pores are consistent with a conformational selection or a slowing down of internal motions that can favor the interaction of the peptide with the receptor.