No 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.

The structural preferences of peptides (and depsipeptides) from the achiral MeAib and Hib residues, and the chiral Iva, (alpha Me) Val, (alpha Me) Leu, and (alpha Me) Phe residues, as determined by conformational energy computations, x-ray diffraction analyses, and 1H-nmr and spectroscopic studies, are reviewed and compared with literature data on Aib-containing peptides. The results obtained indicate that helical structures are preferentially adopted by peptides rich in these alpha-amino acids methylated at the alpha-carbon. Intriguing experimental findings on the impact of the chirality of Iva, (alpha Me) Val, and (alpha Me) Phe residues on helix screw sense are illustrated.

Terminally blocked, isotactic molecular and crystal structures of the Z-trimer is folded in a type I11 /?-turn conhomopeptides from the sterically de-protected trimer, hexamer, heptamer and formation, the longest homopeptides manding a-methylvaline of general for-octamer have been determined by X-ray form well-developed, regular, rightIn the crystal state. while the ed 3,,-helices. The screw sense in the helix Bz, Ac; n = 2-8) have been prepared of the pBrBz-blocked octamer has been step-by-step in solution and fully characconfirmed to be right-handed by solidterized. The conformations preferred in state and solution CD spectroscopy. The possible exploitation of these peptide helices as rigid and precise molecular rulers solution (B-turn and right-handed 3,,-heis discussed.lix) have been assessed by FT-IR, 'HNMR and CD spectroscopy. The