β‐Turn Analogues in Model αβ‐Hybrid Peptides: Structural Characterization of Peptides Containing β2,2Ac6c and β3,3Ac6c Residues
- 3 May 2012
- journal article
- research article
- Published by Wiley in Chemistry – An Asian Journal
- Vol. 7 (7), 1671-1678
- https://doi.org/10.1002/asia.201200052
Abstract
The effect of gem-dialkyl substituents on the backbone conformations of β-amino acid residues in peptides has been investigated by using four model peptides: Boc-Xxx-β2,2Ac6c(1-aminomethylcyclohexanecarboxylic acid)-NHMe (Xxx=Leu ( ), Phe ( ); Boc=tert-butyloxycarbonyl) and Boc-Xxx-β3,3Ac6c(1-aminocyclohexaneacetic acid)-NHMe (Xxx=Leu ( ), Phe ( )). Tetrasubstituted carbon atoms restrict the ranges of stereochemically allowed conformations about flanking single bonds. The crystal structure of Boc-Leu-β2,2Ac6c-NHMe ( ) established a C11 hydrogen-bonded turn in the αβ-hybrid sequence. The observed torsion angles (α(ϕ≈−60°, ψ≈−30°), β(ϕ≈−90°, θ≈60°, ψ≈−90°)) corresponded to a C11 helical turn, which was a backbone-expanded analogue of the type III β turn in αα sequences. The crystal structure of the peptide Boc-Phe-β3,3Ac6c-NHMe ( ) established a C11 hydrogen-bonded turn with distinctly different backbone torsion angles (α(ϕ≈−60°, ψ≈120°), β(ϕ≈60°, θ≈60°, ψ≈−60°)), which corresponded to a backbone-expanded analogue of the type II β turn observed in αα sequences. In peptide , the two molecules in the asymmetric unit adopted backbone torsion angles of opposite signs. In one of the molecules, the Phe residue adopted an unfavorable backbone conformation, with the energetic penalty being offset by a favorable aromatic interaction between proximal molecules in the crystal. NMR spectroscopy studies provided evidence for the maintenance of folded structures in solution in these αβ-hybrid sequences.Keywords
Funding Information
- Department of Biotechnology (DBT), India
This publication has 66 references indexed in Scilit:
- Characteristic Structural Parameters for the γ‐Peptide 14‐Helix: Importance of Subunit PreorganizationAngewandte Chemie, 2011
- Structural Chemistry of Peptides Containing Backbone Expanded Amino Acid Residues: Conformational Features of β, γ, and Hybrid PeptidesChemical Reviews, 2010
- Expanding the Peptide β-Turn in αγ Hybrid Sequences: 12 Atom Hydrogen Bonded Helical and Hairpin TurnsJournal of the American Chemical Society, 2009
- Hybrid αγ Polypeptides: Structural Characterization of a C12/C10Helix with Alternating Hydrogen-Bond PolarityAngewandte Chemie, 2008
- Foldamers with Heterogeneous BackbonesAccounts of Chemical Research, 2008
- Helix Bundle Quaternary Structure from α/β-Peptide FoldamersJournal of the American Chemical Society, 2007
- Expanding the polypeptide backbone: hydrogen-bonded conformations in hybrid polypeptides containing the higher homologues of α-amino acidsJournal of The Royal Society Interface, 2007
- Theoretical prediction of the basic helix types in α,β-hybrid peptidesPeptide Science, 2006
- π-π interactions: the geometry and energetics of phenylalanine-phenylalanine interactions in proteinsJournal of Molecular Biology, 1991
- Aromatic-Aromatic Interaction: A Mechanism of Protein Structure StabilizationScience, 1985