SOLID-STATE AND SOLUTION STRUCTURE OF BOC-L-ALA-DELTA-PHE-DELTA-PHE-NHME - A DEHYDROPEPTIDE SHOWING PROPENSITY FOR 3(10)-HELICES OF BOTH SCREW SENSES

The crystal and molecular structure of the peptide Boc-L-Ala-DELTAPhe- DELTAPhe-NHMe, containing two consecutive dehydro-phenylalanine (DELTA Phe) residues, has been solved by x-ray diffraction. Two independent m olecules, X and Y, are present in the crystallographic unit. Their con formation corresponds approximately to an incipient 3(10)-helix stabil ized by two intramolecular hydrogen bonds. The (phi, psi) torsion angl es, however, have negative and positive signs in the two molecules X a nd Y, respectively. Therefore, in spite of the presence of an amino ac id residue of the L configuration, the two helical molecules have oppo site screw senses, even though the right-handed helix is less distorte d than the left-handed one in correspondence of the L-Ala residue. The CD spectra in various solvents exhibit exciton bands originating from dipole-dipole interaction between the DELTAPhe side chains. Addition of DMSO to the chloroform solution produces, as a first step, a strong increasing of the CD bands, which are then progressively canceled by increasing DMSO concentration. The nmr data parallel the behavior obse rved in the CD spectra. In CDCl3 solution, the temperature coefficient s of the NH resonances are consistent with the involvement of the last two amide protons of the sequence in intramolecular hydrogen bonds, b ut only negligibly small nuclear Overhauser effects (NOE) are observed . Addition of 5% DMSO-d6 allows the observation of diagnostic NOEs. CD and nmr data indicate that the solid state structure is retained in s olution, and are consistent with the presence of right-handed and left -handed conformers, with a prevalence of the more stable right-handed one.