Helix Formation In Peptides Research Articles

Моделирование спирализации пептидов, содержащих в своем составе аспарагиновую или глутаминовую кислоту

Моделирование спирализации пептидов, содержащих в своем составе аспарагиновую или глутаминовую кислоту

Factors governing helix formation in peptides confined to carbon nanotubes.

The effect of confinement on the stability and dynamics of peptides and proteins is relevant in the context of a number of problems in biology and biotechnology. We have examined the stability of different helix-forming sequences upon confinement to a carbon nanotube using Langevin dynamics simulations of a coarse-grained representation of the polypeptide chain. We show that the interplay of several factors that include sequence, solvent conditions, strength (lambda) of nanotube-peptide interactions, and the nanotube diameter (D) determines confinement-induced stability of helicies. In agreement with predictions based on polymer theory, the helical state is entropically stabilized for all sequences when the interaction between the peptide and the nanotube is weakly hydrophobic and D is small. However, there is a strong sequence dependence as the strength of the lambda increases. For an amphiphilic sequence, the helical stability increases with lambda, whereas for polyalanine the diagram of states is a complex function of lambda and D. In addition, decreasing the size of the "hydrophobic patch" lining the nanotube, which mimics the chemical heterogeneity of the ribosome tunnel, increases the helical stability of the polyalanine sequence. Our results provide a framework for interpreting a number of experiments involving the structure formation of peptides in the ribosome tunnel as well as transport of biopolymers through nanotubes.

Spectroscopic Evidence for Backbone Desolvation of Helical Peptides by 2,2,2-Trifluoroethanol: An Isotope-Edited FTIR Study

2,2,2-Trifluoroethanol (TFE) is widely used to induce helix formation in peptides and proteins, but the mechanism behind this effect is still poorly understood. Several recent papers have proposed that TFE acts by selectively desolvating the peptide backbone groups of the helix state. Infrared (IR) spectroscopy of the amide I band of polypeptides can be used to probe both secondary structure and backbone solvation, making this technique well suited for addressing the effect of TFE on polypeptide conformation. In this paper, we report the IR spectra as a function of TFE concentration for an alanine-rich peptide based on the repeat (AAKAA)(n)(). The IR spectra confirm that TFE desolvates the helical state of the peptide to a greater extent than the random coil state. Moreover, using a series of specifically (13)C-labeled peptides, the precise residues desolvated in the presence of TFE were identified. The residues most desolvated by TFE are the alanines located at position i - 4 in the sequence, where i is a lysine residue. This pattern of desolvation is consistent with molecular dynamics simulations which predict strong interactions between the lysine side chain at position n and the backbone carbonyl of the alanine at position i - 4. This is the first direct spectroscopic evidence of specific desolvation of helix backbone atoms in model alanine-rich peptides.

Osmolyte effects on helix formation in peptides and the stability of coiled-coils.

The ability of several naturally occurring substances known as osmolytes to induce helix formation in an alanine-based peptide have been investigated. As predicted by the osmophobic effect hypothesis, the osmolytes studies here do induce helix formation. Trimethylamine-N-oxide (TMAO) is the best structure-inducing osmolytes investigated here, but it is not as effective in promoting helix formation as the common cosolvent trifluoroethanol (TFE). We also provide a semiquantitative study of the ability of TMAO to induce helix formation and urea, which acts as a helix (and protein) denaturant. We find that on a molar basis, these agents are exactly counteractive as structure inducing and unfolding agents. Finally, we extend the investigations to the effects of urea and TMAO on the stability of a dimeric coiled-coil peptide and find identical results. Together these results support the tenets of the osmophobic hypothesis and highlight the importance of the polypeptide backbone in protein folding and stability.

Disrupting Helix Formation in Unsolvated Peptides

Protonated polyalanine peptides form helices in the gas phase when their most basic protonation site (the N-terminus) is blocked by acetylation: Ac-An+H+ (Ac = acetyl and A = alanine). The glycine analogues, Ac-Gn+H+ (G = glycine), on the other hand, form random globules. The disruption of helix formation in unsolvated Ac-AnGxAm+H+ peptides has been examined as a function of n+m, and x using high resolution ion mobility measurements and molecular dynamics simulations. A surprisingly large block of glycine residues is required to disrupt helix formation in these peptides. For example, Ac-A5G3A5+H+ and Ac-A6G5A6+H+ both remain helical at room temperature. According to molecular dynamics simulations, the glycines do not cause a localized disruption of the helices, as might be expected for a residue considered a helix breaker. This is consistent with helix disruption occurring through a global effect on the relative energies of the helix and globule rather than through a localized entropic effect.

Promotion of helix formation in peptides dissolved in alcohol and water-alcohol mixtures

ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTPromotion of helix formation in peptides dissolved in alcohol and water-alcohol mixturesCharles L. Brooks III and Lennart NilssonCite this: J. Am. Chem. Soc. 1993, 115, 23, 11034–11035Publication Date (Print):November 1, 1993Publication History Published online1 May 2002Published inissue 1 November 1993https://doi.org/10.1021/ja00076a089RIGHTS & PERMISSIONSArticle Views204Altmetric-Citations48LEARN ABOUT THESE METRICSArticle Views are the COUNTER-compliant sum of full text article downloads since November 2008 (both PDF and HTML) across all institutions and individuals. These metrics are regularly updated to reflect usage leading up to the last few days.Citations are the number of other articles citing this article, calculated by Crossref and updated daily. Find more information about Crossref citation counts.The Altmetric Attention Score is a quantitative measure of the attention that a research article has received online. Clicking on the donut icon will load a page at altmetric.com with additional details about the score and the social media presence for the given article. Find more information on the Altmetric Attention Score and how the score is calculated. Share Add toView InAdd Full Text with ReferenceAdd Description ExportRISCitationCitation and abstractCitation and referencesMore Options Share onFacebookTwitterWechatLinked InReddit PDF (278 KB) Get e-Alerts Get e-Alerts

Confromational Studies on Peptides Containing Enantiometric α‐Methyl α‐Amino Acids. Part I. Differential conformational properties of (R)‐ and (S)‐2‐methylaspartic acid

AbstractThe conformational properties of four model peptides of the general formula Ac‐Tyr‐Xaa‐Yaa‐Zaa‐Ala‐Lys‐Glu‐ala‐Ala‐Glu‐Lys‐Ala‐Zaa‐Yaa‐Xaa‐Lys‐NH2 (Xaa‐Yaa‐Zaa = Ala‐Ala‐(R)‐Asp(2‐Me), 1; Ala‐Ala‐(S)‐Asp(2‐Me), 2; Ala‐Aib‐Asp, 3; Ala‐Ala‐Asp, 4; Asp(2‐Me) = 2‐methylaspartic acid; Aib = 2‐aminoisobutyric acid) were studied by CD spectroscopy in solution, to evaluate the helix‐inducing potential of enantiomerically pure 2‐methylaspartic acid as a function of its chirality at C(2). At neutral pH and 1°, all peptides exhibit significant helix formation in aqueous solution, the degree of helicity increasing in the order 4 3 ≈ 1. Lowering the pH to 2 results in a dramatic increase in helicity for peptide 1, while the diastereoisomeric peptide 2 now exists in a predominantly unordered conformation. Helix induction by protonated (R)‐Asp(2‐Me) exceeds Aib‐induced helix formation in peptide 3, and the helix content of 1 in aqueous solution at pH 2 is comparable to the degree of helicity in the strongly helix‐inducing solvent 2,2,2‐trifluoroethanol.

The helix–coil transition in heterogeneous peptides with specific side‐chain interactions: Theory and comparison with CD spectral data

Natural and synthetic peptides that contain detectable intramolecular alpha-helical structure in aqueous solution have been used to evaluate the helical propensities for the common amino acids. Experimental spectroscopic data must be fit to a model of the helix-coil transition in order to determine quantitative stability constants for each amino acid. We present here a statistical mechanical description of helix formation in peptides or protein fragments that takes into account multiple internal conformations, heterogeneity in the stabilizing effects of different side chains, and specific side-chain-side-chain interactions. The model enables one to calculate values of [theta]222 for a given peptide using the length dependence of the helix signal computed by a quantum mechanical treatment of the n pi * transition that dominates the 222-nm band. In addition, the helical probability at any residue in the chain is readily computed, and should prove useful as nmr spectral data become available. The free energy of specific side-chain interactions, including ion pair formation, can be evaluated. Application of the analysis to experimental data on a pair of isomeric peptides, only one of which contains ion pairs, indicates that forming a single glutamate-lysine ion pair stabilizes the alpha-helix by 0.50 kcal/mole in 10 mM sodium ion and pH 7. A survey of the CD data measured for a variety of model peptides is presented, indicating that a single set of s values and sigma constant can account for some but not all of the available results.

Folding of a peptide corresponding to the alpha-helix in bovine pancreatic trypsin inhibitor.

A short peptide corresponding to the alpha-helical region of BPTI shows partial folding in aqueous solution (pH 7) as judged by circular dichroism (CD). Folding is temperature and denaturant sensitive, and the peptide is monomeric. The difference CD spectrum, obtained from spectra at two temperatures, indicates that the peptide folds as an alpha-helix. Difference CD spectroscopy provides a sensitive assay for helix formation in peptides exhibiting small amounts of structure. Helix stability in this peptide shows a marked pH dependence which is consistent with stabilizing charged side-chain interactions with the helix dipole and/or salt bridge formation.