Fragmentation reactions of protonated peptides containing phenylalanine: a linear free energy correlation in the fragmentation of H–Gly–Xxx–Phe–OH

Abstract

The fragmentation reactions of a variety of protonated tri- and tetra-peptides containing phenylalanine have been examined using metastable ion studies and energy-resolved collision-induced dissociation studies. For peptides with the sequence H–Gly–Xxx–Phe–OH (Xxx=Gly,Ala,Val,Leu,Phe) the major primary fragmentation of MH + involves cleavage of the C-terminus amide bond to form either the b 2 ion or the y 1″ ion. For metastable ion fragmentation it is found that log([b 2]/[ y 1″]) increases linearly with the increase in the gas phase basicity of H–Xxx–OH. This linear free energy correlation is in contrast to the lack of such a correlation in the fragmentation of protonated H–Gly–Xxx–Gly–OH [J. Mass Spectrom. 30 (1995) 290]. When Phe is the central residue in tripeptides, the major primary fragmentation reaction involves formation of the b 2 ion which fragments further to the a 2 ion; at higher internal energies the a 2 ion fragments to give the phenylalanine immonium ion which becomes the dominant fragment. When Phe is in the N-terminus position, as in Phe–Gly–Gly–OH, the phenylalanine immonium ion is the dominant fragment and is formed, in part, directly by fragmentation of MH +. The fragmentation of the tetrapeptides H–Gly–Gly–Phe–Leu–OH, H–Phe–Gly–Gly–Phe–OH and H–Val–Ala–Ala–Phe–OH are more complex but show a substantial directional effect of the phenylalanine residue(s).