Conformation-Specific Infrared and Ultraviolet Spectroscopy of Cold [YAPAA$+$H]$^{\mathrm{+}}$ and [YGPAA$+$H]$^{\mathrm{+}}$ Ions

Incorporation of the unnatural D-proline stereoisomer into a peptide sequence is a typical strategy to synthesize model $\beta $-hairpin loops. Using conformation-specific IR and UV spectroscopy of cold ($\approx $ 10 K) gas-phase ions, we unravel the inherent conformational preferences of the $^{\mathrm{D}}$P and $^{\mathrm{L}}$P diastereomers in the protonated peptide [YAPAA$+$H]$^{\mathrm{+}}$ because only intramolecular interactions are possible in this isolated regime. Consistent with the solution phase studies, one of the conformers of [YA$^{\mathrm{D}}$PAA$+$H]$^{\mathrm{+}}$ is folded into a $\beta $-hairpin turn. However, a second predominant $\gamma $-turn conformer family is identified. The [YA$^{\mathrm{L}}$PAA$+$H]$^{\mathrm{+}}$ stereoisomer discourages $\beta $-hairpin formation. We show that the \textit{trans }($^{\mathrm{D}}$P)$\to $\textit{cis} ($^{\mathrm{L}}$P) isomerization is sterically driven and can be reversed by substituting [YG$^{\mathrm{L}}$PAA$+$H]$^{\mathrm{+}}$ for [YA$^{\mathrm{L}}$PAA$+$H]$^{\mathrm{+}}$. Therefore, we provide a basis for understanding residue-specific alterations in the potential energy surface and reveal new insights into the origin of $\beta $-hairpin formation from the bottom-up.