Conformational Manifold of -Aminoisobutyric Acid (Aib) Containing Alanine-Based Tripeptides in Aqueous Solution Explored by Vibrational Spectroscopy, Electronic Circular Dichroism Spectroscopy, and Mo
文摘
Replacement of the -proton of an alanine residue to generate -aminoisobutyric acid (Aib) inalanine-based oligopeptides favors the formation of a 310 helix when the length of the oligopeptide is aboutfour to six residues. This research was aimed at experimentally identifying the structural impact of anindividual Aib residue in an alanine context of short peptides in water and Aib's influence on the conformationof nearest-neighbor residues. The amide I band profile of the IR, isotropic and anisotropic Raman, andvibrational 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 thatexploits the excitonic coupling between amide I' modes. The conformational search was guided by therespective 1H NMR and electronic circular dichroism spectra of the respective peptides, which were alsorecorded. From these analyses, all peptides adopted multiple conformations. Aib predominantly sampledthe right-handed and left-handed 310-helix region and to a minor extent the bridge region between thepolyproline (PPII) and the helical regions of the Ramachandran plot. Generally, alanine showed theanticipated PPII propensity, but its conformational equilibrium was shifted towards helical conformations inAc-Aib-Ala-Ala-OMe, indicating that Aib can induce helical conformations of neighboring residues positionedtowards the C-terminal direction of the peptide. An energy landscape exploration by molecular dynamicssimulations corroborated the results of the spectroscopic studies. They also revealed the dynamics andpathways of potential conformational transitions of the corresponding Aib residues.