Conformation-Specific Infrared and Ultraviolet Spectroscopy of Cold [YAPAA+H]~+ and [YGPAA+H]~+ Ions: A Stereochemical 'Twist' on the β-Hairpin Turn

摘要

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 the ~DP and ~LP diastereomers in the protonated peptide [YAPAA+H]~+, where only intramolecular interactions are possible. Consistent with the solution-phase studies, one of the conformers of [YA~DPAA+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 the ~LP diastereomer, [YA~LPAA+H]~+, is found and assigned to a structure that is not the anticipated "mirror image" β-turn. Instead, the ~LP stereocenter promotes a cis-alanine-proline amide bond. The assigned structures contain clues that the preference of the ~DP diastereomer to support a trans-amide bond and the proclivity of ~LP for a cis-amide bond is sterically driven and can be reversed by substituting glycine for alanine in position 2, forming [YG~LPAA+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.