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 ( 2 H, 13 C and 15 N), collision‐induced dissociation (CID) and multiple‐stage tandem mass spectrometry were used to investigate the elimination of H 2 O 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.