A study of the elimination of water from lithium-cationized tripeptide methyl esters by means of tandem mass spectrometry and isotope labeling

Extensive isotope labeling (2H, 13C and 15N), collision‐induced dissociation (CID) and multiple‐stage tandem mass spectrometry were used to investigate the elimination of H2O from a series of model, metal‐cationized tripeptide methyl esters. The present results corroborate our earlier suggestion that loss of water from lithiated peptides is initiated by a nucleophilic attack from the N‐terminal side upon an amide carbonyl carbon atom to form a five‐membered ring as an intermediate followed by 1,2‐elimination of water. We show that the nucleophilic atom is the oxygen atom of the N‐terminal amide group in the fragmentation of [AcGGGOMe+Li]+ as well as [GGGOMe+Li]+. However, the subsequent fragmentation is markedly different in the two cases as a result of the absence and presence of a free amino group. In particular, extensive scrambling of protons in the α‐positions of GGGOMe is observed, presumably as a consequence of intervention of the basic amino group. Copyright © 2006 John Wiley & Sons, Ltd.