Fragmentation chemistry observed in hydrogen deficient radical peptides generated from N-nitrosotryptophan residues

The N-nitrosation reaction has been utilized to add an NO group to the indole nitrogen of tryptophan in several peptides. These peptides can be electrosprayed and then subjected to collision-induced dissociation (CID). The input of CID energy causes the homolytic cleavage of the labile nitrogen–nitrogen single bond resulting in removal of the NO group and generation of a hydrogen deficient peptide radical. This N-nitrosation reaction serves as a simple way to create peptide radicals in the gas phase. Here we examine features of CID for several N-nitrosopeptides and give mechanisms which explain the observed chemistry. In particular, tryptophan side chain loss is frequently an abundant fragmentation channel. Interestingly dissociation of the N–NO bond occurs concomitantly with CO2 loss for peptides with C-terminal tryptophan residues. The location of the nascent radical is an important factor in both of these dissociation pathways. Other fragmentation channels are observed to occur via radical- or proton-catalyzed pathways, depending on the mobility of available protons. Theoretical calculations were also performed to study the energetics of the proposed mechanisms.

Graphical abstractThe dissociation chemistry for peptides containing radical tryptophan is described. One favorable fragmentation channel is the loss of the tryptophan side chain itself.Figure optionsDownload full-size imageDownload high-quality image (53 K)Download as PowerPoint slide