Abstract
The conformational propensities of the Aib residue on the example of two model peptides Ac-Aib-NHMe (1) and Ac-Aib-NMe2 (2), were studied by B3LYP and M06-2X functionals, in the gas phase and in the polar solvents. To verify the reliability of selected functionals, we also performed MP2 calculations for the tested molecules in vacuum. Polarizable continuum models (PCM and SMD) were used to estimate the solvent effect. Ramachandran maps were calculated to find all energy minima. Noncovalent intramolecular interactions due to hydrogen-bonds and dipole attractions between carbonyl groups are responsible for the relative stabilities of the conformers. In order to verify the theoretical results, the available conformations of similar X-ray structures from the Cambridge Crystallographic Data Center (CCDC) were analyzed. The results of the calculations show that both derivatives with the Aib residue in the gas phase prefer structures stabilized by intramolecular N–H⋯O hydrogen bonds, i.e., C5 and C7 conformations, while polar solvent promotes helical conformation with φ, ψ values equal to +/−60°, +/−40°. In addition, in the case of molecule 2, the helical conformation is the only one available in the polar environment. This result is fully consistent with the X-ray data.Graphical abstractEffect of solvent on the Ramachandran maps of the model peptides with Aib residue
Highlights
Achiral α-aminoisobutyryl residue (Aib, α,α-dimethylglycine) is a common component in peptides produced by various microorganisms [1,2,3,4]. gem-Dimethyl substitution on the Cα-atom severely reduces the conformational freedom of this amino acid residue
We present the results of density functional theory (DFT) calculations on the conformational properties of two model peptides with Aib residues: Ac-Aib-NHMe (1) and Ac-Aib-NMe2 (2)
The results of the theoretical calculations presented in this paper highlight the effect of chloroform and water on the conformational properties of model peptides with Aib residue
Summary
Achiral α-aminoisobutyryl residue (Aib, α,α-dimethylglycine) is a common component in peptides produced by various microorganisms [1,2,3,4]. gem-Dimethyl substitution on the Cα-atom severely reduces the conformational freedom of this amino acid residue. Achiral α-aminoisobutyryl residue (Aib, α,α-dimethylglycine) is a common component in peptides produced by various microorganisms [1,2,3,4]. Gem-Dimethyl substitution on the Cα-atom severely reduces the conformational freedom of this amino acid residue. Fungal peptides with proven antibiotic activity containing at least one α,α-dimethylglycine residue are called peptaibiotics [5]. Since the Aib amino acid is not ribosomally encoded, peptides containing this residue are more resistant to proteolytic enzymes than peptides containing protein amino acids only. The Aib residue is used as a modifier of naturally occurring and biologically active peptides [7, 8] due to its unique structural features, introduced by the presence of two methyl groups at Cα
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