Five-membered ring formation in unimolecular reactions of peptides: a key structural element controlling low-energy collision-induced dissociation of peptides

Abstract

Unimolecular fragmentation reactions of peptides in low-energy collision-induced dissociation are reviewed in the mechanistic context of five-membered ring formation. This structure of intermediates or of fragment ions is recognized as a key element that governs unimolecular peptide fragmentation within the structural framework determined by the peptide backbone and its side-chains. A collection of collision-induced dissociation reactions is presented covering (i) b-ion formation, (ii) the fragmentation of N -terminally acylated peptides, (iii) neutral loss of the C -terminal amino acid in alkali or silver cationized peptides, (iv) the fragmentation of isoAsp-containing peptides and (v) the fragmentation of negatively chargedAsp-or Glu-containing peptides. It appears that for all possible nucleophile-electrophile interactions leading to a five-membered ring structure an associated unimolecular peptide fragmentation reaction can be observed.

Selective identification and quantitative analysis of methionine containing peptides by charge derivatization and tandem mass spectrometry

“…Under low-energy collisional activation conditions, the cleavage of most bonds within a protonated peptide ion is thought to require localization of an ionizing proton at the cleavage site. Fragmentation then proceeds via "charge-directed" neighboring group participation mechanisms involving nucleophilic attack from an adjacent functional group [51][52][53][54]. The formation of product ions resulting from "enhanced" cleavage at the N-terminal side of proline residues has been consistently noted in the literature, presumably because of the higher local proton affinity of the proline imide bond compared with a conventional amide bond.…”

“…Intramolecular transfer of an acidic proton present in either the precursor ion (Pathway 1), or in the product ion formed following methionine side chain cleavage (Pathway 2a or 2b) would result in "mobilization" of this proton, thereby allowing it to be involved in subsequent fragmentation reactions according to the mobile proton model developed for rationalizing the fragmentation of protonated peptide ions [51][52][53][54][55][56]. Note that if the reaction proceeds via Pathway 2 of Scheme 4, the amide bond incorporated into the cyclic product would not be amenable to subsequent cleavage.…”

Discrimination Between Peptide O-Sulfo- and O-Phosphotyrosine Residues by Negative Ion Mode Electrospray Tandem Mass Spectrometry

“…Table 2). The unusually facile expulsion of water from 6a is induced by N-terminal location of Glu, the side chain of which can rapidly interact with the N-terminal peptide amine to form a stable cyclic amide structure [38].…”

Electrospray ionisation-cleavable tandem nucleic acid mass tag–peptide nucleic acid conjugates: synthesis and applications to quantitative genomic analysis using electrospray ionisation-MS/MS

“…Thus, this pair of tags allows a pair of PNA probes to be distinguished by MS/MS analysis. Each tag is linked to a PNA oligonucleotide probe by a second linker, comprising aspartic acid and proline that is easily cleaved by CID (37). As shown in Figure 2, the aspartic acid/proline linker is used to cleave the tags from their oligonucleotides during electrospray ionization of the tagged oligonucleotides.…”