3(10)-Helices, helix screw sense and screw sense reversal in the dehydro-peptide Boc-Val-delta Phe-Gly-delta Phe-Val-OMe.
The pentapeptide Boc-Val-delta Phe-Gly-delta Phe-Val-OME, containing two dehydro-phenylalanine (delta Phe) residues, has been synthesized and its structure investigated. In the crystalline state, the molecule adopts a right-handed 3(10)-helical conformation stabilized by two intramolecular hydrogen bonds between CO of Val1 and NH of delta Phe4, and between CO of delta Phe2 and NH of Val5, respectively. NMR measurements are consistent with the presence of 3(10)-helical structures also in acetonitrile and dimethylsulphoxide solution: the distances between backbone protons estimated from NOE connectivities are in overall agreement with those observed in the solid state; the chemical shifts of the amide protons show the smaller temperature coefficients for the NHs that in solid state are involved in intramolecular hydrogen bonds. The CD spectra in acetonitrile, chloroform, methanol and dimethylsulphoxide display exciton couplets of bands corresponding to the delta Phe electronic transition at 280 nm; the sign of the bands is consistent with the presence of helical structures having a prevalent left-handed screw sense. Addition of 1,1,1,3,3,3-hexafluoro-propan-2-ol gives rise to the gradual appearance of a couplet of opposite sign, suggesting the helix reversal from left-handed sense to right-handed sense. The conformational behaviour is discussed on the basis of the specific sequence of the peptide.