[Babcock_Hall]

Based partially on my own experience, I am given to understand that detection of phosphopeptides can be difficult in mass spectrometry and that part of the problem lies with the negative charge(s) introduced by this post-translational modification.  I was wondering whether or not trying to methylate the phosphate group (so that it would be a dimethylester) would be worth trying.  All I found out in searching was one paper in which the authors apparently produced methyl esters of carboxylic acids using methanol/HCl and detected the phosphopeptides in negative ion mode.

Some years ago enzymologists used to create methyl esters of derivatives of phosphoric acid for certain stereochemical experiments IIRC.  The reagent was probably diazomethane.  Perhaps this is not practical to use in peptide analysis.  Thoughts?