3(10)-Helices, helix screw sense and screw sense reversal in the dehydro-peptide Boc-Val-delta Phe-Gly-delta Phe-Val-OMe

Title pentapeptide Boc-Val-ΔPhe-Gly-ΔPhe-Val-OMe [Boc = Me3CO2C; ΔPhe = (Z)-dehydrophenylalanine] has been synthesized and its structure investigated. In the cryst. state, the mol. adopts a right-handed 310-helical conformation stabilized by two intramol. hydrogen bonds between CO of Val1 and NH of ΔPhe4, and between CO of ΔPhe2 and NH of Val5, resp. NMR measurements are consistent with the presence of 310-helical structures also in acetonitrile and DMSO soln.: the distances between backbone protons estd. from NOE connectivities are in overall agreement with those obsd. in the solid state; the chem. shifts of the amide protons show the smaller temp. coeffs. for the NHs that in solid state are involved in intramol. hydrogen bonds. The CD spectra in acetonitrile, chloroform, methanol and DMSO display exciton couplets of bands corresponding to the ΔPhe 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. Addn. 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 behavior is discussed on the basis of the specific sequence of the peptide.