Depsipeptide Analogues of Gly-Ala-Gly: Proton Localization and Effects on Collision-Induced Dissociation

Depsipeptides are peptides that contain both amino acid and hydroxy acid residues. In this study, we sought to investigate how terminal hydroxyl groups and/or backbone ester linkages from hydroxy acid residues in depsipeptides affected collision-induced dissociation (CID). The canonical tripeptide glycine-alanine-glycine (GAG) was compared to all three of its depsipeptide analogues: glycolic acid-AG (gAG), G-lactic acid-G (GaG), and GA-glycolic acid (GAg). Experimental data was supported by density functional theory (DFT) calculations to gain insight into which sites on the molecules have sufficient proton affinity (PA) to localize the proton and the resulting charge-directed fragmentation processes.