Special feature: Commentary - Mobile and localized protons: a framework for understanding peptide dissociation

Protein identification and peptide sequencing by tandem mass spectrometry r equires knowledge of how peptides fragment in the gas phase, specifically w hich bonds are broken and where the charge(s) resides in the products. For many peptides, cleavage at the amide bonds dominate, producing a series of ions that are designated b and y, For other peptides, enhanced cleavage occ urs at just one or two amino acid residues, Surface-induced dissociation, a long with gas-phase collision-induced dissociation performed under a variet y of conditions, has been used to refine the general 'mobile proton' model and to determine how and why enhanced cleavages occur at aspartic acid resi dues and protonated histidine residues. Enhanced cleavage at acidic residue s occurs when the charge is unavailable to the peptide backbone or the acid ic side-chain. The acidic H of the side-chain then serves to initiate cleav age at the amide bond immediately C-terminal to Asp (or Glu), producing an anhydride, In contrast, enhanced cleavage occurs at His when the His side-c hain is protonated, turning His into a weak acid that can initiate backbone cleavage by transferring a proton to the backbone. This allows the nucleop hilic nitrogen of the His side-chain to attack and form a cyclic structure that is different from the 'typical' backbone cleavage structures. Copyrigh t (C) 2000 John Wiley & Sons, Ltd.