Conformational manifold of α-aminoisobutyric acid (Aib) containing alanine-Based tripeptides in aqueous solution explored by vibrational spectroscopy, electronic circular dichroism spectroscopy, and molecular dynamics simulations

Schweitzer-Stenner, Reinhard, Gonzales, Widalys, Bourne, Gregory T., Feng, Jianwen A. and Marshall, Garland R. (2007) Conformational manifold of α-aminoisobutyric acid (Aib) containing alanine-Based tripeptides in aqueous solution explored by vibrational spectroscopy, electronic circular dichroism spectroscopy, and molecular dynamics simulations. Journal of the American Chemical Society, 129 43: 13095-13109. doi:10.1021/ja0738430


Author Schweitzer-Stenner, Reinhard
Gonzales, Widalys
Bourne, Gregory T.
Feng, Jianwen A.
Marshall, Garland R.
Title Conformational manifold of α-aminoisobutyric acid (Aib) containing alanine-Based tripeptides in aqueous solution explored by vibrational spectroscopy, electronic circular dichroism spectroscopy, and molecular dynamics simulations
Journal name Journal of the American Chemical Society   Check publisher's open access policy
ISSN 0002-7863
1520-5126
Publication date 2007-10
Sub-type Article (original research)
DOI 10.1021/ja0738430
Volume 129
Issue 43
Start page 13095
End page 13109
Total pages 15
Place of publication Washington, D.C., United States
Publisher American Chemical Society
Language eng
Subject 030606 Structural Chemistry and Spectroscopy
030602 Chemical Thermodynamics and Energetics
030503 Organic Chemical Synthesis
030406 Proteins and Peptides
Abstract Replacement of the α-proton of an alanine residue to generate α-aminoisobutyric acid (Aib) in alanine-based oligopeptides favors the formation of a 310 helix when the length of the oligopeptide is about four to six residues. This research was aimed at experimentally identifying the structural impact of an individual Aib residue in an alanine context of short peptides in water and Aib's influence on the conformation of nearest-neighbor residues. The amide I band profile of the IR, isotropic and anisotropic Raman, and vibrational circular dichroism (VCD) spectra of Ac-Ala-Ala-Aib-OMe, Ac-Ala-Aib-Ala-OMe, and Ac-Aib-Ala-Ala-OMe were measured and analyzed in terms of different structural models by utilizing an algorithm that exploits the excitonic coupling between amide I‘ modes. The conformational search was guided by the respective 1H NMR and electronic circular dichroism spectra of the respective peptides, which were also recorded. From these analyses, all peptides adopted multiple conformations. Aib predominantly sampled the right-handed and left-handed 310-helix region and to a minor extent the bridge region between the polyproline (PPII) and the helical regions of the Ramachandran plot. Generally, alanine showed the anticipated PPII propensity, but its conformational equilibrium was shifted towards helical conformations in Ac-Aib-Ala-Ala-OMe, indicating that Aib can induce helical conformations of neighboring residues positioned towards the C-terminal direction of the peptide. An energy landscape exploration by molecular dynamics simulations corroborated the results of the spectroscopic studies. They also revealed the dynamics and pathways of potential conformational transitions of the corresponding Aib residues.
Keyword Potential conformational transitions
Carboxylic acids
2 amino 2 methylpropionic acid
Aminoisobutyric acids
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Excellence in Research Australia (ERA) - Collection
ERA 2012 Admin Only
Institute for Molecular Bioscience - Publications
 
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Created: Tue, 10 Feb 2009, 16:54:54 EST by Ms Sarada Rao on behalf of Institute for Molecular Bioscience