Sensitivity improvement of amino acids by N-terminal

With the introduction of a diisopropyloxyphosphoryl group (DIPP) at the N terminus of amino acids, it was found that the signal response in electrospray ionization mass spectrometry enhanced by factors of 10-100 folds in positive mode and much higher in negative mode. Enhancement on proton affinity (PA) by N-terminal DIPP derivatization of native amino acids, was supported by kinetic method experiments, which might be responsible for the sensitivity improvement in positive mode. Two different mechanisms, which include the gas-phase acidity increase of amino acids resulted from the electron withdrawing ability of DIPP group and pH effect on the formation of anion ions of amino acids and their phosphorylation derivatives, were studied to explain the signal response enhancement in negative mode. This sensitivity improvement method might have some potential for the amino acid detection in mass spectrometry, or even the peptide sequencing in proteomics.