Fragmentation of tunichrome Sp‐1 is dominated by an unusual gas‐phase intramolecular rearrangement

Abstract

Tunichrome Sp-1 is a modified pentapeptide from the ascidian Styela plicata, having the structure H-DOPA-DOPA-Gly-Pro-dcDeltaDOPA (where DOPA = 3,4-dihydroxyphenylalanine and dcDeltaDOPA = decarboxy-(E)-alpha,beta-dehydro-DOPA). The tandem mass spectrum of the peptide is dominated by a number of abundant fragment ions that involve a gas-phase rearrangement where the dcDeltaDOPA group becomes covalently attached to the N-terminus. The high degree of rearrangement in Sp-1 compared with a related octapeptide, plicatamide, allowed for detailed multiple mass spectrometric (MS(n)) (up to n = 6) experiments, and hence permitted a detailed assessment of the origin and routes to the formation of the various rearrangement ions. Analyses on both a triple-quadrupole and a quadrupole time-of-flight mass spectrometer were made to ascertain whether the gas-phase rearrangements observed for tunichrome Sp-1 were unique to an ion trap mass spectrometer (i.e. the hypothesis being that perhaps the extended trapping times were required to facilitate this unusual gas-phase rearrangement). Interestingly, analyses on both the triple-quadrupole and quadruple time-of-flight mass spectrometers revealed an identical phenomenon, with the rearrangement fragment ions present at approximately the same abundance as the non-rearranged a-, b- and y-type sequence ions. We suggest that the smaller size of tunichrome Sp-1 compared with plicatamide facilitates the transfer of the dcDeltaDOPA group in this gas-phase rearrangement. This rearrangement was not observed for peptide analogs of tunichrome Sp-1 that did not contain the dcDeltaDOPA at the C-terminus, confirming that the presence of dcDeltaDOPA is critical for the rearrangement.

Gas-Phase Rearrangement of the O-Glucuronide of Vildagliptin Forms Product-Ion Fragments Suggesting Wrongly an N-Glucuronide

“…Migrations where a carbon atom and not a heteroatom had to be reattached before the internal losses are less common. Migration of 4-(2aminovinyl)benzene-1,2-diol has been observed in tunichrome 8, a pentapeptide containing two such moieties, and these ions were much larger with an ion trap instrument than with triple quandrupole (Taylor et al, 2003). Another example is migration of a methyl group from an aromatic methoxy group in 9 to a nitrogen in negative ionization mode (Tiller et al, 2001).…”

Cyclization reaction of peptide fragment ions during multistage collisionally activated decomposition: An inducement to lose internal amino-acid residues

“…The bottom-up sequencing requires MS/MS analysis of the proteolytic fragments and database searching using algorithms such as Mascot and Sequest [5,6]. In addition, structural elucidations of natural or synthetic peptides, including linear peptides [7,8], cyclic peptides [9,10], and peptide analogues [11] also rely on MS/MS analysis. Undoubtedly, all of the applications described above are based on understanding the dissociation mechanisms of peptides, which have been well summarized in recent reviews [12][13][14][15][16].…”

A Molecular Modeling Investigation of the Therapeutic Potential of Marine Compounds as DPP-4 Inhibitors

“…Moreover, the binding pose and interactions of CMNPD13046 were consistent in all three structures, which lends further support to the results (Figure 2C). The bioactive molecule CMNPD13046 is tunichrome Sp-1, a modified pentapeptide found in the hemocytes of the ascidian Styela plicata, with the structure H-DOPA-DOPA-Gly-Pro-dc∆DOPA, where DOPA = 3,4-dihydroxyphenylalanine and dc∆DOPA = decarboxy-(E)-α,β-dehydro-DOPA [19,20]. It is a low-molecular-weight linear peptide with a number of properties including metal chelation, sequestration of vanadium or iron, wound healing and antibacterial activity [21,22].…”