Tlpe gas-phase structures and fragmentation pathways of the N-terminal b and a fragments of YAGFL-NH2, AGLFY-NH2, GFLYA-NH2, FkYAG-NH2, and LYAGF-NH2 were investigated using collision-induced dissociation (CID) and detailed molecular mechanics and density functional theory (DFT) calculations. Our combined experimental and theoretical approach allows probing of the scrambling and rearrangement reactions that take place in CID of b and a ions. It is shown that low-energy CID of the b5 fragments of the above peptides produces nearly the same dissociation patterns. Furthermore, CID of protonated cycto-(YAGFL) generates the same fragments with nearly identical ion abundances when similar experimental conditions are applied This suggests that rapid cyclization of the primarily linear b5 ions takes place and that the CID spectrum is indeed determined by the fragmentation behavior of the cyclic isomer This can open up at various amide bonds, and its fragmentation behavior can be understood only by assuming a multitude of fragmenting linear structures. Our computational results fully support this cyclization-reopening mechanism by showing that protonated cyc/o-(YAGFL) is energetically favored over the linear ?>5 isomers. Furthermore, the cyclization-reopening transition structures are energetically less demanding than those of conventional bond-breaking reactions, allowing fast interconversion among the cyclic and linear isomers. This chemistry can lead in principle to complete loss of sequence irfformation upon CID, as documented for the b5 ion of FLYAG-NH2 CID of the a5 ions of the above peptides produces fragment ion distributions that can be explained by assuming ?>-type scrambling of their parent population and a - a*-type rearrangement pathways (Vachet, R, W.; Bishop, B. M.; Erickson, B. W; Glish, G. L. J. Am. Chem, Soc 1997, 119, 5481). While a ions easily undergo cyclization, the resulting macrocycle predominantly reopens to regenerate the original linear structure. Computational data indicate that the a - a*-type rearrangement pathways of the linear a isomers involve post-cleavage proton-bound dimer intermediates in which the fragments reassociate and the originally C-terminal fragment is transferred to the N-terminus.
展开▼
