Observation of a Crossed Double β-Turn in a Capped ^DPro-Gly-Ala Tripeptide: One-to-One Correspondence between X-ray Crystallography, 2D-NMR, and Gas-Phase Laser Spectroscopy

Herein, we report for the first time a direct correspondence between the observation of a β-turn or a crossed double β-turn in the Boc- D Pro-Gly-Ala-NHBn-OMe ( D PGA) tripeptide by using a combination of X-ray crystallography, 2D-NMR spectroscopy, and gas-phase laser spectroscopy supported by quantum chemistry calculations. Type-II′ and type-I double β-turns, involving the D PG and GA moieties of D PGA, respectively, are observed in both condensed-phase and gas-phase experiments. Additionally, a low-energy conformer of D PGA featuring a triple γ-turn backbone is detected in the gas-phase. This work also marks the first-ever observation of a type II′ β-turn involving D PG in a polypeptide within the gas-phase. The type II′ β-turn plays a crucial role in β-hairpin formation in polypeptides and proteins, whereas the type I β-turn is the most common structural feature, enabling a 180° reversal of polypeptide chains in proteins. Furthermore, our analyses of the Cambridge Structural Database (CSD) and Protein Data Bank (PDB) reveal that the crossed double β-turn structural motif is widely present in both peptides and proteins. A comprehensive investigation of this tripeptide’s secondary structural motif, derived from both condensed-phase and gas-phase studies, highlights the localized nature of secondary structures. This reinforces the significance of the intrinsic folding tendencies of amino acid residues in determining the peptide conformation.