On the Thermal Stability of -Peptides: A Two-Dimensional Vibrational Spectroscopy Study

Abstract

Professor Dieter Seebach in Bewunderung und mit den besten W¸nschen zum 65. Geburtstag gewidmet.A temperature-dependent 2D-IR study of the amide-I band of a b-peptide forming a 12/10/12/10 helix is presented. Cross-relaxation of a spectrally separated marker amide-I mode, which could be assigned with the help of the NMR structure of the molecule, can be used as measure of conformational flexibility of the molecule. We find that the conformational flexibility of the N-terminal part of the helix increases slightly upon increasing the temperature from 08 to 808. The cross-peaks in the 2D-IR spectrum, and hence the connectivity of the corresponding peptide units, do not change, suggesting that the N-terminal part of the helix remains essentially intact at 808. This conclusion is in agreement with previous NMR and CD measurements.Introduction. ± Protein folding is the process of transferring information from one dimension into three dimensions, where the information that determines the molecular structure of a protein is encoded in its amino acid sequence. Understanding the mechanism by which the amino acid sequence of a protein folds into its unique native conformation is one of the biggest challenges in biophysical chemistry.The major degrees of freedom of the polypeptide chain are two s-bonds in each amino acid, which can freely rotate. The amide group (i.e., ÀCOÀNHÀ ) itself is close to planar since the CÀN bond has partial double-bond character. The free-energy surface of the two-dimensional configuration space of each amino acid has been extensively studied. A complicated balance of different forces results in two main local free-energy minima, which are of almost equal depth. Because of the large dimensionality of the problem in polypeptides and proteins, and because of the

Nonlinear two-dimensional vibrational spectroscopy of peptides

“…The i are the intrinsic excitation energies of the individual sites, and the β i j are the couplings between sites. Owing to its simple and physically very intuitive picture, the exciton model is now commonly used to interpret 2D-IR experiments [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33]. The traditional, and by far more common, picture, however, to describe molecular vibrations is that of normal modes [41,42].…”

Use of vibrational spectroscopy to study protein and DNA structure, hydration, and binding of biomolecules: A combined theoretical and experimental approach

“…This work has been one of the cornerstones for further developments. Other cornerstones have recently been put down by the recent collaborative multidimensional IR experiments performed in the laboratories of P. Hamm in Switzerland 117, S. Woutersen in Berlin, Germany 118–120, and G. Stock in Frankfurt, Germany 121. By performing two photon experiments one is able to determine which vibrational modes are coupled.…”

General Applicable Frequency Map for the Amide-I Mode in β-Peptides

“…14−26 On the other hand, increasing interests have been seen in recent years for establishing a relationship between the spectral and structural features of β-peptides. 27,28 Femtosecond 2D IR spectroscopy has been used to reveal the structural dynamics of a 12/10-helical β-peptide, 29 and a βpeptide model compound N-ethylpropionamide (NEPA) that has a single amide unit. 28 Nanosecond time-resolved IR with temperature-jump has been used to study the folding mechanism of a helical β-peptide.…”

“…As for β-sheet, there are two peaks located at ca . 1630 and 1680 cm –1 respectively, and the low-frequency peak has stronger absorption than the high-frequency counterpart. ,,− Femtosecond two-dimensional infrared (2D IR) spectroscopy developed in recent years has greatly enhanced the knowledge of the amide-I vibration of α-peptides, by, for example, being able to structurally decipher a network of vibrational coupling between different amide-I vibrators. − On the other hand, increasing interests have been seen in recent years for establishing a relationship between the spectral and structural features of β-peptides. , Femtosecond 2D IR spectroscopy has been used to reveal the structural dynamics of a 12/10-helical β-peptide, and a β-peptide model compound N -ethylpropionamide (NEPA) that has a single amide unit . Nanosecond time-resolved IR with temperature-jump has been used to study the folding mechanism of a helical β-peptide .…”