Effect of the ΔPhe residue configuration on a didehydropeptides conformation: A combined CD and NMR study

Abstract

Conformations of two pairs of dehydropeptides with the opposite configuration of the ∆Phe residue, Boc-Gly-∆ Z Phe-Gly-Phe-OMe (Z-OMe), Boc-Gly-∆ E Phe-Gly-Phe-OMe (E-OMe), BocGly-∆ Z Phe-Gly-Phe-p-NA (Z-p-NA), and Boc-Gly-∆ E Phe-Gly-Phe-p-NA (E-p-NA) were compared on the basis of CD and NMR studies in MeOH, TFE, MeCN, chloroform, and DMSO. The CD results were used as the additional input data for the NMR-based determination of the detailed solution conformations of the peptides. It was found that E-OMe is unordered and Z-OMe, Z-p-NA, and E-p-NA adopt the β-turn conformation. There are two overlapping β-turns in each of those peptides: type II and type III' in Z-OMe and Z-p-NA, and two type III in E-p-NA. The ordered structure-inducing properties of ∆ Z Phe and ∆ E Phe in the peptides studied depend on the Cterminal blocking group. In methyl esters the ∆ Z Phe residue is a strong inducer of ordered conformations whereas the ∆ E Phe one has no such properties. In p-nitroanilides, both isomers of ∆Phe cause the peptides to adopt ordered structures to a similar extent.

Influence of solvents on conformation of dehydropeptides

“…The strong positive bands at 220 nm and strong and broad negative bands at 270 nm are observed only for peptide Boc-Gly-Gly-D Z PhePhe-OMe in acetonitrile and methanol solutions. Such kind of spectra, as it was indicated before [58], is typical for tetrapeptide which is adopting type II b-turn, with DPhe at the i + 2 position. Also in case of tetrapeptide 2 the same tendency, which was show for tripeptide 1, to adopt less ordered conformation in less polar solvent is observed.…”

“…Secondary structure, adopted by hexapeptide 3 in DMSO, is stabilized by two intramolecular hydrogen bonds, which involved amide protons of Phe [3] and Gly [4] residues. Although temperature factor of the amide proton of Phe [3] is slightly bigger than 4.6 (ppb/K), we suggest that this proton participates in hydrogen bond formation, because chemical shift of this proton demonstrate significant independence from solvent polarity [58] (see Table 9). Obtained results for the tripeptide 1 and tetrapeptide 2 are similar to those obtained previously for their structural analogues containing E-isomer of DPhe [60].…”

Self‐Synthesizing Models of Helical Proteins Based on Aromatic Disulfide Chemistry

“…Calculations of the lowest‐energy structures, carried out for the TASP molecules which exhibited ordered conformations in solution according to CD, were performed with an X‐PLOR NIH 2.21 program package . We used the same calculation procedure as in the conformational investigations of dehydropeptides . Each of 1000 structures was calculated using simulated annealing (initial temperature=1000 K, final temperature=100 K).…”

A general method for preparation of N‐Boc‐protected or N‐Fmoc‐protected α,β‐didehydropeptide building blocks and their use in the solid‐phase peptide synthesis

“…They contain a double bond between the C α and C β carbon atoms which results in their planar conformation and fixed values of the φ and ψ torsion angles. These features endow them with particular conformational properties . Recently, it has been found that peptides with α,β‐didehydro‐α‐amino acid residues can form hydrogels and may be used as a platform for drug delivery which make these residues important for medicinal chemistry.…”