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.