The two peptides, rich in Calfatetrasubstituted amino acids, Ac-[AibL-(alfaMe)Val-Aib]2-l-His-NH2 (1) and Ac-[Aib-L-(alfaMe)Val-Aib]2-O-tBu (2a) are prevalently helical. They present the unique property of changing their conformation from the alfa- to the 3 10-helix as a function of the polarity of the solvent: a in more polar solvents, 3 10 in less polar ones. Conclusive evidence of this reversible change of conformation is reported on the basis of the circular dichroism (CD) spectra and a detailed two-dimensional NMR analysis in two solvents (trifluoroethanol and methanol) refined with molecular dynamics calculations. The X-ray diffractometric analysis of the crystals of both peptides reveals that they assume a prevalent 3 10-helix conformation in the solid state. This conformation is practically superimposable on that obtained from the NMR analysis of 1 in methanol. The NMR results further validate the reported CD signature of the 3 10-helix and the use of the CD technique for its assessment.
