Conformational Characterization of Terminally Blockedl-(αMe)Val Homopeptides Using Vibrational and Electronic Circular Dichroism. 310-Helical Stabilization by Peptide−Peptide Interaction

Abstract

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.