title: Conformation-Specific Infrared and Ultraviolet Spectroscopy of Cold [YAPAA+H]+and [YGPAA+H]+Ions: A Stereochemical "Twist" on the β-Hairpin Turn.
abstract: Incorporation of the unnatural d-proline (DP) stereoisomer into a polypeptide sequence is a typical strategy to encourage formation of β-hairpin loops because natural sequences are often unstructured in solution. Using conformation-specific IR and UV spectroscopy of cold (≈10 K) gas-phase ions, we probe the inherent conformational preferences of theDP andLP diastereomers in the protonated peptide [YAPAA+H]+, where only intramolecular interactions are possible. Consistent with the solution-phase studies, one of the conformers of [YADPAA+H]+is folded into a charge-stabilized β-hairpin turn. However, a second predominant conformer family containing two sequential γ-turns is also identified, with similar energetic stability. A single conformational isomer of theLP diastereomer, [YALPAA+H]+, is found and assigned to a structure that is not the anticipated "mirror image" β-turn. Instead, theLP stereocenter promotes a cis-alanine-proline amide bond. The assigned structures contain clues that the preference of theDP diastereomer to support a trans-amide bond and the proclivity ofLP for a cis-amide bond is sterically driven and can be reversed by substituting glycine for alanine in position 2, forming [YGLPAA+H]+. These results provide a basis for understanding the residue-specific and stereospecific alterations in the potential energy surface that underlie these changing preferences, providing insights to the origin of β-hairpin formation.
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Andrew F
authors.identifier: 0000-0002-5274-9078
authors.initials: AF
authors.lastname: DeBlase
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Christopher P
authors.initials: CP
authors.lastname: Harrilal
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: John T
authors.initials: JT
authors.lastname: Lawler
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Burke
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Scott A
authors.identifier: 0000-0002-1648-5570
authors.initials: SA
authors.lastname: McLuckey
authors.affiliation: Department of Chemistry, Purdue University , West Lafayette, Indiana 47907-2084, United States.
authors.forename: Timothy S
authors.identifier: 0000-0002-4468-5748
authors.initials: TS
authors.lastname: Zwier
mesh_terms: D007477:Ions / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D011392:Proline / Q000737:chemistry*; D011487:Protein Conformation; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism
chemical_list: D007477:Ions; D010455:Peptides; D011392:Proline