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Updated: May 14, 2026

Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
Introduction of cyclically constrained γ-residues stabilizes an α-peptide hairpin in aqueous solution
George A Lengyel1, Geoffrey A Eddinger, W Seth Horne
1Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, United States.
Abstract:
The synthesis and structural characterization of hybrid α/γ-peptides resulting from a 1:1 α→γ residue substitution at cross-strand positions in a hairpin-forming α-peptide sequence are described. Cyclically constrained γ-residues based on 1,3-substituted cyclohexane or benzene scaffolds support a native-like hairpin fold in aqueous solution, and the unnatural residues stabilize the folded state by ∼0.2 kcal/mol per α→γ substitution.
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