Electron transfer dissociation of multiply protonated and fixed charge disulfide linked polypeptides

Multiply protonated disulfide linked peptides and fixed charged analogs have been subjected to electron transfer ion/ion reactions to examine the role of excess protons in inducing cleavage of the disulfide bond in electron transfer dissociation. Systems in which all of the excess charge was due to fixed charge sites (i.e., quaternary ammonium groups) showed somewhat more disulfide bond cleavage than the fully protonated species. This observation argues against a major role for a mechanism that requires hydrogen transfer to the disulfide bond as a prerequisite for its cleavage. Interestingly, species with mixed cation sites (one or more excess protons and one or more fixed charge side chains) showed lower propensities for disulfide bond cleavage than either the corresponding fully protonated or fully derivatized species. This observation is not likely to be accounted for by direct electron transfer to a Coulomb stabilized disulfide bond because the identities of the charge bearing sites are not expected to play a significant role in the degree of stabilization. The results appear to be best rationalized on the basis of the 'through bond electron transfer' mechanism of Simons et al., in conjunction with rate limiting intramolecular electron transfer(s) between charge bearing sites. Intramolecular electron transfer between charge sites can play a role in mediating electron movement from the site of initial electron capture to the site from which an electron is transferred to the disulfide anti-bonding orbital. (C) 2007 Elsevier B.V. All rights reserved.