Involvement of salt bridges in a novel gas phase rearrangement of protonated arginine-containing dipeptides which precedes fragmentation

A novel gas phase rearrangement reaction has been discovered for [M + H](+) ions of arginine-containing dipeptides. In the case of Gly-Arg and Arg-Gly, this leads to identical tandem mass spectra (MS/MS) thereby precluding their sequence assignment. Density functional theory (DFT) calculations and further multistage mass spectrometry experiments suggest a mechanism which involves the formation of salt bridges for Gly-Arg and Arg-Gly which then undergo ring closure followed by ring opening to form a mixed anhydride. Prevention of salt bridge formation switches off this reaction and yields different MS/MS spectra which allow sequence assignment. This can be achieved by preforming CID on the deprotonated dipeptides or their protonated methyl esters.