Thermal Stability of Dehydrophenylalanine‐Containing Model Peptides as Probed by Infrared Spectroscopy: a Case Study of an α‐Helical and a 3₁₀‐Helical Peptide

Abstract

The temperature-dependent secondary-structural changes in the two known helical model peptides Boc-Val-deltaPhe-Ala-Leu-Gly-OMe (1; alpha-helical) and Boc-Leu-Phe-Ala-deltaPhe-Leu-OMe (2; 3(10)-helical), which both comprise a single dehydrophenylalanine (deltaPhe) residue, were investigated by means of FT-IR spectroscopy (peptide film on KBr). Both the first-order and the better-resolved second-order derivative IR spectra of 1 and 2 were analyzed. The nu(NH) (3240-3340 cm(-1)), the Amide-I (1600-1700 cm(-1)), and the Amide-II (1510-1580 cm(-1)) regions of 1 and 2 showed significant differences in thermal-denaturation experiments (22 degrees --> 144 degrees), with the 3(10)-helical peptide (2) being considerably more stable. This observation was rationalized by different patterns and strengths of intramolecular H-bonds, and was qualitatively related to the different geometries of the peptides. Also, a fair degree of residual secondary-structural elements were found even in the 'denatured' states above 104 degrees (1) or 134 degrees (2).

pH and Substrate Effect on Adsorption of Peptides Containing Z and E Dehydrophenylalanine. Surface-Enhanced Raman Spectroscopy Studies on Ag Nanocolloids and Electrodes

“…In addition, ligands with the phenyl ring in the Z configuration show distinctly higher ability of metal ion binding through nitrogen atoms, when compared to peptides with Δ (E) Phe. , The deprotonated carboxylic group also participates in coordination of the metal ions, but this interaction is much weaker for the Z isomer of ΔPhe than the E counterpart due to the steric hindrance. This effect was observed to be stronger for short peptides. , Recently, several experimental and theoretical studies on molecular structure of dehydropeptides have been reported, but they have been focused mainly on the analysis of IR, , circular dichroism, NMR spectra, and X-ray diffraction − supported by quantum-chemical calculations. , Up to now, the Raman and SERS profiles of short peptides containing dehydroamino acid residues have been studied by our group only. , In our previous work we reported IR, Raman, and SERS spectra of three dipeptides Boc-Gly-X, where X is ΔAla, Δ (Z) Phe, and Δ (E) Phe. SERS spectra were collected by using Ag sol as a metal substrate.…”

“…Additionally, the ΔPhe moiety exists in the two isomeric forms, Z and E, which can influence the biological activity of the peptide. 8 This class of nonproteinogenic amino acids can be found in many biological peptides with antiviral, antitumor, anti-inflammatory, or immunosuppressive activities. 9,10 Dehydroamino acids are also used in de novo synthesis of protein mimics for structure−function relationship studies.…”

“…This effect was observed to be stronger for short peptides. 13,14 Recently, several experimental and theoretical studies on molecular structure of dehydropeptides have been reported, but they have been focused mainly on the analysis of IR, 8,15 circular dichroism, 16 NMR spectra, 15 and X-ray diffraction 15−17 supported by quantum-chemical calculations. 18,19 Up to now, the Raman and SERS profiles of short peptides containing dehydroamino acid residues have been studied by our group only.…”

“…The presence of this bond decreases the conformational flexibility of proteins. Additionally, the ΔPhe moiety exists in the two isomeric forms, Z and E , which can influence the biological activity of the peptide . This class of nonproteinogenic amino acids can be found in many biological peptides with antiviral, antitumor, anti-inflammatory, or immunosuppressive activities. , Dehydroamino acids are also used in de novo synthesis of protein mimics for structure–function relationship studies. , In addition, potentiometric and electronic absorption studies on coordination ability of dehydropeptides toward Ni(II) and Cu(II) ions have shown that the presence of the double C α C β bond makes the dehydropeptides more efficient ligands than the parent peptides. , These dehydropeptides form various coordination modes, in which N atoms of the N-terminal amino group and of amide bonds are usually metal binding sites.…”

Handedness preference and switching of peptide helices. Part II: Helices based on noncodedα‐amino acids

“…Spectroscopic measurements were extensively employed for the assessment of the local (NMR) and overall (IR absorption) conformational properties of ΔPhe‐rich peptides in solution; although with these compounds, CD spectroscopy (refer to later in the text) proved by far to be the technique of choice. In particular, IR absorption studies were not only conducted in solvents of low polarity but also extended to the solid state (KBr film, ZnSe crystal surface, Ag nanocolloids, and electrodes) as well, where related spectroscopies (Raman, surface‐enhanced Raman scattering, and vibrational CD) were also utilized . These analyses were expanded to N α ‐methylated ΔPhe residues where the cis tertiary amide conformation was shown to prevail.…”