Can the (M•-X) region in electron capture dissociation provide reliable information on amino acid composition of polypeptides?

It has been suggested that small losses from reduced peptide molecular species in electron capture dissociation (ECD) could indicate the presence of certain amino acids [H.J. Cooper, R.R. Hudgins, K. Hakansson and A.G. Marshall, J. Am. Soc. Mass Spectrom. 13, 241 (2002)], similarly to immonium ions in high-energy collision-activated dissociation. The diagnostic value in ECD of the (M. - X) region (1 Da less than or equal to X less than or equal to 130 Da) was tested on several synthetic peptides. The insufficiency of the existing knowledge for making correct conclusions on the amino acid composition is demonstrated and new suggestions of the origin of losses are presented based on the "hot hydrogen atom" ECD mechanism. Generally, it is shown that not only protonation but also charge solvation is responsible for the small losses. The origin of 17 Da and 59 Da losses is revisited and a new mechanism for the 18 Da loss is suggested. The loss of a side chain plus a hydrogen atom is found to be a rather reliable indicator of the presence of histidine, tryptophan, tyrosine and, to a lesser degree, threonine. The overall conclusion is that the (M. - X) region does contain information on the amino acid composition, but extraction of this information requires additional studies.