Vibrational and electronic circular dichroism (VCD and ECD) and Fourier transform infrared (FTIR) spectra of the homo-oligopeptide series Z-[l-(αMe)Val] n -OtBu (n = 3−8) and selected Ac-[l-(αMe)Val] n -OtBu oligomers (n = 4, 6, 8) are presented. This is the first VCD study of a complete homopeptide series formed exclusively by Cα-methylated amino acids. VCD spectra were measured for the oligomers in 2,2,2-trifluoroethanol (TFE) and CDCl3 over the amide I and amide II spectral regions (1750−1475 cm-1). These oligopeptides, irrespective of the N-terminal group, were found to indicate formation of at least a partially 310-helical conformation for main-chain lengths as short as n = 4 and a fully developed 310-helix by n = 6 at high peptide concentrations. A 310-helical conformation for the octamer is consistent with previous spectroscopic studies and crystallographic results. The ECD spectra were measured for the oligomer series in TFE and 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) over the 260−190 nm region. The ECD spectra, again for both Nα-blocking groups, indicate a helical structure for the octamer, a mixed ordered/unordered structure at n = 6, and a predominantly coil form for n = 4. The octamer ECD band shape and FTIR absorption maximum are concentration dependent. At higher concentrations, the ECD mimics that which has been associated with a 310-helical conformation, while at lower concentrations the ECD is more typical of an α-helix. A study of the octamer in HFIP indicates a gradual transition from the 310-like to α-helical-like ECD spectra with time. While indicating the need for further study, these data are the first evidence of the possibility of a 310-helix to α-helix equilibrium shift induced by a change in peptide−peptide interactions, with aggregation favoring the 310-helical form.

Vibrational circular dichroism (VCD) and Fourier transform IR (FTIR) were measured for a series of short alanine-based peptides having the general formula Ac-(AAKAA)n-GY-NH2 (n = 1-4) from 5 to 50 degrees C in D2O and at room temperature in both TFE and H2O. In both of these latter solvents, the dominant structural form at the lowest temperature for the longest oligomers is alpha-helical. The same is true for the n = 4 peptide in D2O, but under these more dilute aqueous conditions, the shorter (n = 3) peptides have mixed helix-coil structures and the n = 1 and 2 peptides are random coils. The VCD data do not support the 310-helix as a dominant contributor to the conformation of these oligomers in any of these solvents. These vibrational spectral data are consistent with lower-concentration electronic CD results and additionally indicate increased helical stability at higher concentrations. VCD amide I data for the 22mer (n = 4) in D2O indicate that the peptide undergoes a transition from a highly helical conformation at 5 degrees C to a dominant random coil structure at approximately 45 degrees C with a Tm of approximately 25 degrees C (effective midpoint). Factor analysis of the thermal data showed that three principal components were required to describe both the VCD and FTIR data for the n = 4 peptide in D2O. The transition is characterized by a gradual loss of contribution from a spectral component representing the alpha-helical fraction. The third component is evidence of an optically detected intermediate conformation best viewed as a mixed coil-helix structure resulting from end fraying of the helical peptide as the temperature is increased. The nature of the junction between the interior helix and frayed ends is not determined by these data and could involve local (phi and psi) angles mimicking a 310-helix that would provide consistency with ESR and NMR results from Millhauser and co-workers.

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Terminally blocked (L-Pro-Aib)n and Aib-(L-Pro-Aib)n sequential oligopeptides are known to form right-handed beta-bend ribbon spirals under a variety of experimental conditions. Here we describe the results of a complete CD and ir characterization of this subtype of 3(10)-helical structure. The electronic CD spectra were obtained in solvents of different polarity in the 260-180 nm region. The vibrational CD and Fourier transform ir (FTIR) spectra were measured in deuterochloroform solution in the amide I and amide II (1750-1500 cm-1) regions. The critical chain length for full development of the beta-bend ribbon spiral structure is found to be five to six residues. Spectral effects related to concentration-induced stabilization of the structures of the longer peptides were seen in the resolution-enhanced FTIR spectra. Comparison to previous studies of (Aib)n and (Pro)n oligomers indicate that the low frequency of the amide I mode is due to the interaction of secondary and tertiary amide bonds and not to a strong difference in conformation from a regular 3(10)-helix.