The types and intensities of tandem mass spectrometric products of side-chain interactions were investigated with a hybrid tandem instrument. Positive-ion unimolecular decomposition and collisionally activated decomposition studies were conducted on the [ M + HI + ions of two N-benzyloxycarbonyl (Cbz or Z)-protected tripeptides, Cbz-Gly-Leu-Arg-NH, and Cbz-Gly-Pro-Arg-NH, . The loss of benzyl alcohol (108 u) and the formation of other significant product ions and their dependence on collision energy and gas pressure suggest reaction between both ends of the molecule. Replacement of leucine with proline at the second position in the tripeptide produces a very intense [M + H -1081' ion and fewer lower mass fragment ions in the tandem mass spectra for Cbz-Gly-Pro-Arg-NH, than in those for Cbz-Gly-Leu-Arg-NH, . 157 132 -cH2Nz\ /' -NH3 115 Scheme 2. Pathways to formation of m/z 11 5 (y, -CH5N,) for Cbz-G ly-Leu -Arg -N H, .pathway, which is less likely, involves first the loss of CH2N, to form m/z 132, with a subsequent ammonia loss to form m/z 115. The tandem mass spectra of the deuterated analog confirm these assignments. 157