This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.The mechanism of electron capture dissociation is a matter of substantial debate at the moment. Several years ago, we published a paper which showed that ECD of doubly charged cyclic peptides generated a very large number of secondary fragments and thus proposed a 'free-radical cascade' mechanism. One of the premises of this mechanism is that a radical is formed (no debate there) and that it survives for a long time (microseconds to milliseconds) before initiating bond cleavages. If this is true, synthetically attaching a group which could stabilize a radical should reduce cleavages. In order to test this hypothesis, coumarin groups were attached to substance P peptides, and the ECD spectra of these modified peptides were generated. The addition of the coumarin tags eliminated backbone cleavages, but enhanced sidechain cleavages, which supports the FRC mechanism. This paper was published in the Journal of the American Society for Mass Spectroetry.A second fixed-charge derivative that modifies lysine into a pyridinyl group has been investigated with similar results.
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