Peptide foldamers as building blocks for ordered nanomolecular architectures - A structural investigation

The determination of the structural features of ordered, sterically constrained peptides (foldamers) in solution, in membrane phase and supported onto appropriate surfaces can be performed making use of a technique less powerful but cheaper than NMR, having a high potentiality. This method combines the results of time-resolved FRET (fluorescence resonance energy transfer) measurements with those of molecular mechanics calculations. Once the structure of the main chain has been evaluated by other spectroscopic techniques, such as IR and CD, the deepest energy minimum conformers can be obtained by molecular mechanics, so that the theoretical interprobe distance and orientation and their relative population can be compared with those obtained by time-resolved fluorescence experiments. Where comparison between calculated and measured quantities is successful, a good piece of structural information is obtained, otherwise the experimental results can be used as constraints for structural calculations. By applying this technique to a number of peptides or bioactive pseudopeptides in solution (mainly methanol or water/methanol) or in model membranes (liposomes), we were able to determine, with a high degree of confidence, their structure. Some of these structures were later confirmed by X-ray diffraction data in the solid state. The application of this method to some peptides is presented and discussed.