Discriminating 3₁₀‐ from α‐helices: Vibrational and electronic CD and IR absorption study of related Aib‐containing oligopeptides

Abstract

Model peptides based on -(Aib-Ala)(n)-, and (Aib)(n)-Leu-(Aib)(2) sequences, which have varying amounts of 3(10)-helical character, were studied by use of vibrational and electronic circular dichroism (VCD and ECD) and Fourier transform infrared (FTIR) absorption spectroscopies to test the correlation of spectral response and conformation. The data indicate that these peptides, starting from a length of about four to six residues, predominantly adopt a 3(10)-helical conformation at room temperature. The longest model peptides, depending on the series, may evidence some alpha-helical contribution to the spectra, while the shorter ones, with less than six residues, have much less order. The IR absorption spectra (as supported by theory) showed only small frequency changes between 3(10)- and alpha-helices. By contrast, solvent effects are a source of much bigger perturbations. The ECD results show that the intensity ratio for the approximately 222-nm to approximately 208-nm bands, while useful for distinguishing between these two helical types in some sequences, may have a narrower range of application than VCD. However, the VCD data presented here continue to support the proposed discrimination between alpha- and 3(10)-helices based on qualitative amide I and II bandshape differences. The present study shows the intensities of the 3(10)-helical amide I (peak-to-peak) to its amide II VCD to be of the same order and useful for discriminating them from alpha-helices, whose amide I dominates the amide II in intensity. This qualitative result is experimentally independent of the amount of alphaMe-substituted residues in the sequence. These experimental VCD results are consistent in detail with theoretical spectral simulations for Ac-(Ala)(8)-NH(2), Ac-(Aib-Ala)(4)-NH(2), and Ac-(Aib)(8)-NH(2) in 3(10)- and alpha-helical conformations.

Structures of plant viruses from vibrational circular dichroism

“…A b-sheet structure exhibits a small negative VCD band near 1620 cm 21 (amide I) and a negative VCD couplet in the amide II region. Characteristic VCD patterns in the amide I region for the 3 10 -helix, b-turn and polyproline II structures have also been reported (Zhao et al, 2000;Silva et al, 2002).…”

“…A b-sheet structure exhibits a small negative VCD band near 1620 cm 21 (amide I) and a negative VCD couplet in the amide II region. Characteristic VCD patterns in the amide I region for the 3 10 -helix, b-turn and polyproline II structures have also been reported (Zhao et al, 2000;Silva et al, 2002).Since water absorbs strongly in the infrared region, it is not a favourable solvent for IR absorption and VCD spectroscopy. One approach to overcoming this limitation is to use higher sample concentrations and minimize the interference from solvent absorption.…”

Unique amalgamation of primary and secondary structural elements transform peptaibols into potent bioactive cell-penetrating peptides

“…Each of the new products showed increased potency in PANC-1 cells relative to 1 (SI Appendix, Table S19). The effect was most highly pronounced when aromatic moieties (e.g., phenyl, biphenyl, naphthyl, coumarin, anthracene, and anthraquinone) (33)(34)(35)(36)(37)(38)(39) were introduced. In contrast, the coumarin-linked analog of alamethicin (43) exhibited only a minor increase in potency in PANC-1 cells (GI 50 6.75 μM for alamethicin and GI 50 structural features of the gichigamins were essential to the overall unique biological activity of this group of peptaibols.…”

Signatures of β-sheet secondary structures in linear and two-dimensional infrared spectroscopy

“…[27][28][29][30] For modestly larger systems, ab initio calculations for smaller portions of the system can be combined to build up a model of the spectroscopy. [31][32][33] These investigations are providing a better description of the influence of the local configuration and bonding on amide vibrational couplings. Although studies on larger systems with secondary structure exist, 23,26 there have been no systematic 2DIR investigations on proteins, because the interpretation of IR spectra for complex secondary and tertiary structures is still quite difficult.…”