Different Spectral Signatures of Octapeptide 3₁₀- and α-Helices Revealed by Two-Dimensional Infrared Spectroscopy

Femtosecond two-dimensional infrared (2D IR) spectroscopy is applied to the amide I modes of the terminally protected homo-octapeptide Z-[L-(alphaMe)Val](8)-OtBu in CDCl(3), 2,2,2-trifluoroethanol (TFE), and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) solutions to acquire 2D spectral signatures that distinguish between 3(10)- and alpha-helix structures. Suppression of diagonal peaks by controlling polarizations of IR pulses clearly reveals cross-peak patterns that are crucial for structural determination. A doublet feature is observed when the peptide ester forms a 3(10)-helix in CDCl(3) and TFE and when it is at the initial stage of 3(10)- to alpha-helix transition in HFIP. In contrast, the 2D IR spectrum shows a multiple peak pattern after the peptide ester has acidolyzed and become an alpha-helix in HFIP. Electronic circular dichroism spectra accompanying the acidolysis-driven conformational change are also reported. This is the first report on the experimental 2D IR signature of a 3(10)-helical peptide. These results, using a model octapeptide, demonstrate the powerful capability of 2D IR spectroscopy to discriminate between different helical structures.