title: Impact of γ-Amino Acid Residue Preorganization on α/γ-Peptide Foldamer Helicity in Aqueous Solution.
abstract: α/γ-Peptide foldamers containing either γ(4)-amino acid residues or ring-constrained γ-amino acid residues have been reported to adopt 12-helical secondary structure in nonpolar solvents and in the solid state. These observations have engendered speculation that the seemingly flexible γ(4) residues have a high intrinsic helical propensity and that residue-based preorganization may not significantly stabilize the 12-helical conformation. However, the prior studies were conducted in environments that favor intramolecular H-bond formation. Here, we use 2D-NMR to compare the ability of γ(4) residues and cyclic γ residues to support 12-helix formation in more challenging environments, methanol and water. Both γ residue types support 12-helical folding in methanol, but only the cyclically constrained γ residues promote helicity in water. These results demonstrate the importance of residue-based preorganization strategies for achieving stable folding among short foldamers in aqueous solution.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors.forename: Brian F
authors.initials: BF
authors.lastname: Fisher
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D000072756:Protein Conformation, alpha-Helical; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012996:Solutions; D014867:Water / Q000737:chemistry*
chemical_list: D000596:Amino Acids; D010455:Peptides; D012996:Solutions; D014867:Water