Refining the model for selective cleavage at acidic residues in arginine-containing protonated peptides

Simple glycine-based peptides containing acidic [aspartic (D) and glutamic acid (R)] and basic residues [arginine (R)] were dissociated by surface-induced dissociation (SID) both in a tandem double quadrupole (Q(1)Q(2)) and a hybrid sector/time-of-flight (TOF) mass spectrometer, as well as by low-energy collision-induced dissociation in an ion trap mass spectrometer. The synthetic peptides investigated were G (D) under bar GGG (D) under bar G, G (D) under bar GGG (D) under bar GR, RG (D) under bar GGG (D) under bar G, RG (D) under bar GGG (D) under bar GR, GGG (D) under bar GR, GGG (E) under bar GR, and G (D) under bar GGG (E) under bar GR. The mass spectral results obtained support and extend our previous findings that selective cleavages at the C-(O)-N bond adjacent to the acidic residues (C-side) predominate in the spectra when the number of ionizing protons equals or is less than the number of arginine residues. They also support our conclusion that these cleavages are induced by the side-chain acidic hydrogens of D or E residues. Stochastic molecular modeling procedures have been employed in this work to probe the gas-phase conformations for these protonated peptides. These searches have revealed possible conformers of singly protonated GGG (D) under bar GR, and RG (D) under bar GGG (D) under bar G peptide ions where the protonated arginine is solvated by nearby carboxylic and carbonyl oxygens along with simultaneous intramolecular H bonding between the D side-chain acidic hydrogen(s) and the adjacent C-side peptide bonds. Electrospray ionization/surface-induced dissociation fragmentation efficiency curves (percent Fragmentation versus SID laboratory collision energy) are also presented for some of these peptides. The relative position of these curves both with the Q(1)Q(2) and sector/TOF instruments along with less pronounced selective cleavages for the E-containing peptides support our previous conclusion that selective cleavage at E residues require longer time frames for dissociation than for D-containing peptides. The total sum of these findings underscores the idea that gas-phase secondary structure (i.e, conformation) can have an influence in peptide fragmentation. (C) 2000 Elsevier Science B.V.