title: A γ-amino acid that favors 12/10-helical secondary structure in α/γ-peptides.
abstract: H-bonded helices in conventional peptides (containing exclusively homochiral α-amino acid residues) feature a uniform H-bonding directionality, N-terminal side C═O to C-terminal side NH. In contrast, heterochiral α-peptides can form helices in which the H-bond directionality alternates along the backbone because neighboring amide groups are oriented in opposite directions. Alternating H-bond directions are seen also in helices formed by unnatural peptidic backbones, e.g., those containing β- or γ-amino acid residues. In the present study, we used NMR spectroscopy and crystallography to evaluate the conformational preferences of the novel γ-amino acid (1R,2R,3S)-2-(1-aminopropyl)-cyclohexanecarboxylic acid (APCH), which is constrained by a six-membered ring across its Cα-Cβ bond. These studies were made possible by the development of a stereoselective synthesis of N-protected APCH. APCH strongly enforces the α/γ-peptide 12/10-helical secondary structure, which features alternating H-bond directionality. Thus, APCH residues appear to have a conformational propensity distinct from those of other cyclically constrained γ-amino acid residues.
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison , Madison, Wisconsin 53706, United States.
authors.forename: Michael W
authors.initials: MW
authors.lastname: Giuliano
authors.forename: Stacy J
authors.initials: SJ
authors.lastname: Maynard
authors.forename: Aaron M
authors.initials: AM
authors.lastname: Almeida
authors.forename: Li
authors.initials: L
authors.lastname: Guo
authors.forename: Ilia A
authors.initials: IA
authors.lastname: Guzei
authors.forename: Lara C
authors.initials: LC
authors.lastname: Spencer
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000596:Amino Acids / Q000737:chemistry*; D003509:Cyclohexanecarboxylic Acids / Q000737:chemistry; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D017433:Protein Structure, Secondary
chemical_list: D000596:Amino Acids; D003509:Cyclohexanecarboxylic Acids; D010455:Peptides; C044895:cyclohexanecarboxylic acid