Characterization of alkylated and modified peptides by Fourier transform ion cyclotron resonance mass spectrometry

Gas-phase reactions between xenobiotics cysteine S-conjugates and anionic bases were examined using Fourier transform ion cyclotron resonance mass spectrometry. The evidence in the literature suggests that action by enzymes such as $b$-lyase releases thiolates and other reactive intermediates by deprotonating the cysteine conjugates. The reactions studied were chosen to model the release of such reactive and possibly cytotoxic species from the cysteine S-conjugates. Examining cysteine S-conjugates in the gas phase makes it possible to observe directly the formation of the thiolates and thiiranes.; The various haloethenes show distinctive patterns of toxicity and mutagenicity thought to be correlated with the nature of the $b$-lyase-induced decompositions. In particular 2-bromo-1,1,2-trifluorothene shows a mutagenicity not shown by the 2-chloro and 2-fluoro compounds. It has been proposed that this mutagenicity is correlated with a greater propensity of the Br compound to form thiirane. This propensity to form thiirane is consistent with the present gas phase results, which show the Br compound to have a greater propensity to form thiirane on anionic base-induced elimination.; The anionic bases examined react in the gas-phase with compound A-derived cysteine S-conjugates to form an enolate intermediate followed by elimination of either a thiolate anion or HF. Release of thiolate from the Compound A-derived cysteine S-conjugates might inactivate enzymes by alkylating them or otherwise reacting irreversibly with them.; CID spectra on the (M-H)− negative ion of sulfur and disulfide containing peptides are dominated by the loss of the alkyl thiol or the cleavage of sulfur-sulfur bond, in contrast to the CID of the positive ions where S-S bond cleavage is a minor process. In addition, CID of the negative ion of the disulfides reveal selective fragmentations pertinent to its secondary structure in the gas phase. Specifically, hydrogen bonding across the disulfide bridge is required to account for the CID results.; Fragmentation patterns and the energy dependence of the CID fragmentation patterns of two isomeric peptides were probed in search of a means to distinguish the isomers. Subtle but definitive differences were observed in the behaviors of the isomers.