title: Conformation-specific spectroscopy of capped glutamine-containing peptides: role of a single glutamine residue on peptide backbone preferences.
abstract: The conformational preferences of a series of short, aromatic-capped, glutamine-containing peptides have been studied under jet-cooled conditions in the gas phase. This work seeks a bottom-up understanding of the role played by glutamine residues in directing peptide structures that lead to neurodegenerative diseases. Resonant ion-dip infrared (RIDIR) spectroscopy is used to record single-conformation infrared spectra in the NH stretch, amide I and amide II regions. Comparison of the experimental spectra with the predictions of calculations carried out at the DFT M05-2X/6-31+G(d) level of theory lead to firm assignments for the H-bonding architectures of a total of eight conformers of four molecules, including three in Z-Gln-OH, one in Z-Gln-NHMe, three in Ac-Gln-NHBn, and one in Ac-Ala-Gln-NHBn. The Gln side chain engages actively in forming H-bonds with nearest-neighbor amide groups, forming C8 H-bonds to the C-terminal side, C9 H-bonds to the N-terminal side, and an amide-stacked geometry, all with an extended (C5) peptide backbone about the Gln residue. The Gln side chain also stabilizes an inverse γ-turn in the peptide backbone by forming a pair of H-bonds that bridge the γ-turn and stabilize it. Finally, the entire conformer population of Ac-Ala-Gln-NHBn is funneled into a single structure that incorporates the peptide backbone in a type I β-turn, stabilized by the Gln side chain forming a C7 H-bond to the central amide group in the β-turn not otherwise involved in a hydrogen bond. This β-turn backbone structure is nearly identical to that observed in a series of X-(AQ)-Y β-turns in the protein data bank, demonstrating that the gas-phase structure is robust to perturbations imposed by the crystalline protein environment.
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana 47901, USA. zwier@purdue.edu.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Walsh
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana 47901, USA. zwier@purdue.edu.
authors.forename: Jacob C
authors.initials: JC
authors.lastname: Dean
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: McBurney
authors.affiliation: Department of Chemistry, Ajou University, Republic of Korea.
authors.forename: Hyuk
authors.initials: H
authors.lastname: Kang
authors.affiliation: Department of Chemistry, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana 47901, USA. zwier@purdue.edu.
authors.forename: Timothy S
authors.initials: TS
authors.lastname: Zwier
mesh_terms: D005973:Glutamine / Q000737:chemistry*; D010455:Peptides / Q000737:chemistry*; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
chemical_list: D010455:Peptides; D005973:Glutamine