ESI-MSⁿstudy on the fragmentation of protonated cyclic-dipeptides

Abstract

Cyclic dipeptides are relatively simple compounds that can exhibit a great variety of important biological activities. The fragmentation pathways of protonated cyclic dipeptides have been studied by electrospray ionization multistage mass spectrometry (ESI-MSn). The mass spectra studies of the cyclic dipeptides showed that the cyclic dipeptides with the similar substituents, the side chains of amino acid residues at the diketopiperazine ring, followed the same fragmentation pathway. In the fragmentation spectra of protonated cyclic dipeptides, some characteristic fragment ions were observed and could be used to distinguish the cyclic dipeptides. The hydrogen/deuterium (H/D) exchange experiment and the high-resolution mass spectrometry (Q-TOF) were used to verify and rationalize the proposed fragmentation pathways. These observations may have some potential applications in the structural elucidation and interpretation of the mass spectra of homologous compounds.

Comparative studies on similarities and differences of cyclodipeptide oxidases for installation of C–C double bonds at the diketopiperazine ring

“…In a previous study, fragment F (Fig. 5) was observed as major peaks in the MS 2 spectra of phenylalanine-and tyrosine-containing CDPs (Guo et al 2009), which was confirmed in this study by detection of ions at m/z 120.08 and 136.07 in 1a, 1b, 2a, and 2c (Table S7, Fig. S52 and Fig.…”

“…Specific MS 2 fragmentation patterns of cyclodipeptides have been reported (Furtado et al 2007;Guo et al 2009). In order to find the key MS fragments of dehydrogenated CDPs, we used incubation mixtures of the three CDOs with 1a-3a for MS 2 analysis (Figs.…”

The aspartimide problem persists: Fluorenylmethyloxycarbonyl‐solid‐phase peptide synthesis (Fmoc‐SPPS) chain termination due to formation of N‐terminal piperazine‐2,5‐diones

“…Although Electrospray ionization‐Mass spectrometry (ESI‐MS) studies of cyclic dipeptides are described in literature, we were not able to discriminate between the two possible cyclic structures (ie, six‐ vs seven‐membered ring) by MS. Therefore, the nature of this side reaction was not known when we initiated our investigations .…”

“…To the best of our knowledge, there is no published study describing whether a six-or seven-membered species or a mixture is formed and to what extent this side-reaction occurs. 12,13 Although Electrospray ionization-Mass spectrometry (ESI-MS) studies of cyclic dipeptides are described in literature, 14 we were not able to discriminate between the two possible cyclic structures (ie, six-vs seven-membered ring) by MS. Therefore, the nature of this side reaction was not known when we initiated our investigations.…”

Simultaneous determination of hydrophobicity and dissociation constant for a large set of compounds by gradient reverse phase high performance liquid chromatography–mass spectrometry technique

“…phenyl salicylate degradation to salicylic acid and phenol), poor solubility or primarily ionization problems. The ESI is more aggressive ion source than, for example APCI, and it is reported [27,28] that ionization of some of the compounds could lead to fragmentation preventing their observation in the MS spectrum. Some of the analyzed substances (e.g.…”