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The dehydropeptide Ac-delta Phe-L-Val-delta Phe-NH-Me, containing two dehydrophenylalanine (delta Phe) residues, crystallizes from methanol/water in space group P212121, with a = 12.622 (1), b = 12.979 (1), and c = 15.733 (1) A. In the solid state, the molecular structure is characterized by the presence of two intramolecular hydrogen bonds which form two consecutive beta-bends. The (phi, psi) torsion angles of the three residues are very similar and close to the standard values of type III beta-bends, so the molecular conformation corresponds to an incipient right-handed 3(10)-helix, only slightly distorted. In the crystal, the molecules are linked by head-to-tail hydrogen bonds, thus forming continuous helical columns packed in antiparallel mode. There are no lateral hydrogen bonds; the only interactions are hydrophobic contacts between the apolar side chains of neighboring helical columns.

Dehydropeptide analogs of dermorphin (H-Tyr-D-Ala-Phe-Gly-Tyr-Pro-Ser-NH2) and N-terminal fragments containing one or two dehydrophenylalanine residues in the 3rd and/or 5th position, have been investigated by means of CD spectroscopy. The results indicate that the above dehydropeptides can adopt different conformations in alcohol and water solutions. In methanol and trifluoroethanol, the CD spectra are mainly consistent with the presence of folded structures, probably stabilized by intramolecular hydrogen bonds. In water, conversely, CD data indicate disruption of ordered structures and formation of preferentially extended flexible conformations. Models of the involved folded structures are tentatively proposed, taking into account the geometric features of dehydro residues and their tendency to favor hydrogen-bonded 10-membered rings.

Eleven unsaturated peptides, containing one or two dehydro-phenylalanyl (dehydro-Phe) residues and a C-terminal L-amino acid have been hydrogenated in the presence of palladium-on-charcoal. Hydrolysis of the saturated peptides thus obtained gave optically active phenylalanine showing the occurrence of asymmetric induction during the hydrogenation. Both mono-unsaturated dipeptides and doubly unsaturated tripeptides with L-Glu, L-Leu and L-Val as chiral end-group afforded L-Phe in 40-50% optical yield. In the case of the tripeptide N-acetyl-(dehydro-Phe)-(dehydro-Tyr)-L-Glu the asymmetric induction was higher (70%) for the unsaturated residue which is farther from the chiral end-group along the peptide chain. The results are discussed on the bases of Prelog rule and the rigid dissymmetric conformation of the dehydropeptides in solution.