Electron capture dissociation of disulfide, sulfur-selenium, and diselenide bound peptides

To examine the electron capture dissociation (ECD) behavior of disulfide (S-S), sulfur-selenium (S-Se), and diselenide (Se-Se) bonds-containing peptides, a series of free cysteine (Cys) and selenocysteine (Sec) containing peptides were reacted to form interchain S-S, S-Se, and Se-Se bonds, and then studied using ECD with Fourier transform ion cyclotron mass spectrometry (FTICR MS). These results demonstrate that the radical has higher tendency to stay at selenium rather than sulfur after the cleavage of Se-S bonds by ECD. In addition, -SH (-33), -S (-32), and -S + H (-31) small neutral losses were all observed from the cleavage of C-S bonds of a disulfide bound peptide. Similar, but minor, fragments were also detected in S-Se bound peptides. In contrast, the cleavage of C-Se bonds of the Se-Se species mainly forms fragments with neutral loss of -Se + H (-78.90868), and the radical tends to stay on the selenium of its corresponding complementary pair. Although the electron affinities of S atom (2.07 eV) and Se atom (2.02 eV) are very close; they have very different reactivity towards electrons. The replacement of sulfur with selenium greatly increases the electron affinities of S-Se and Se-Se bonds comparing to S-S bonds (with an increase of electron affinity by about 0.20 eV by replacing a sulfur with a selenium) (Int J Quantum Chem 110:513-523, 2010), which in turn leads to different ECD fragmentation behavior and mechanisms. Our results are in good agreement with previously published ab initio calculations on Se-Se compounds by other groups.