Negative ion cleavages of (M–H)⁻ anions of peptides. Part 3. Post‐translational modifications

Abstract

It is now 25 years since we commenced the study of the negative-ion fragmentations of peptides and we have recently concluded this research with investigations of the negative-ion chemistry of most post-translational functional groups. Our first negative-ion peptide review (Bowie, Brinkworth, & Dua, 2002) dealt with the characteristic backbone fragmentations and side-chain cleavages from (M-H) ions of underivatized peptides, while the second (Bilusich & Bowie, 2009) included negative-ion backbone cleavages for Ser and Cys and some initial data on some post-translational groups including disulfides. This third and final review provides a brief summary of the major backbone and side chain cleavages outlined before (Bowie, Brinkworth, & Dua, 2002) and describes the quantum mechanical hydrogen tunneling associated with some proton transfers in enolate anion/enolate systems. The review then describes, in more depth, the negative-ion cleavages of the post-translational groups Kyn, isoAsp, pyroglu, disulfides, phosphates, and sulfates. Particular emphasis is devoted to disulfides (both intra- and intermolecular) and phosphates because of the extensive and spectacular anion chemistry shown by these groups. © 2016 Wiley Periodicals, Inc. Mass Spec Rev.

FT‐MS in the de novo top‐down sequencing of natural nontryptic peptides

“…Due to higher yields of negative ions such peptides may be easier detected in the mixtures. The rules of fragmentation of negative peptide ions are well studied by J. Bowie group (Bowie et al, 2002;Bilusich & Bowie, 2009;Wang et al, 2018). Although CID of negatively charged peptides often results in predominant losses of small molecules (H 2 O, CO 2 , phosphate groups), SORI-CID sometimes can be rather useful (Ewing & Cassady, 2001).…”

Sequencing of Sulfopeptides Using Negative-Ion Tandem Mass Spectrometry with Hydrogen Attachment/Abstraction Dissociation

“…In contrast, de novo sequencing using tandem mass spectrometry (MS/MS) is still essential for protein characterization, especially for the determination of the site of post-translational modification. Collision-induced dissociation (CID) is the most widely available fragmentation method for MS/MS and is used for the characterization of peptide-containing acidic PTM . However, labile PTM, including sulfonation, is usually lost during the CID fragmentation process, and CID is not suitable for determining the location of sulfonation sites in sulfopeptides.…”

“…Collision-induced dissociation (CID) is the most widely available fragmentation method for MS/MS and is used for the characterization of peptide-containing acidic PTM. 8 However, labile PTM, including sulfonation, is usually lost during the CID fragmentation process, and CID is not suitable for determining the location of sulfonation sites in sulfopeptides.…”

Negative Ion Mode Collision-Induced Dissociation for Analysis of Protein Arginine Methylation

“…It is reasonable to assume that MS-based analysis of protein PTMs combining both positive and negative polarities could enhance considerably the robustness of the experimental data in comparison with that of generated through the exclusive use of the positive ion mode approach. So far, only a very limited number of protein PTMs (phosphorylation, sulfation, intramolecular disulfide bridging, and several more [23, 24, 41–46]) can be examined using negative polarity MS/MS, because of the lack of knowledge available on decomposition channels of the corresponding negatively charged modified peptides. Here, for the first time, we report the negative ion mode CID chemistry of Arg methylated peptides demonstrating the potential of the negative polarity MS/MS for the analysis of protein arginine methylation.…”