A novel derivatization method for peptides to increase sensitivity and backbone fragmentation in liquid secondary-ion mass spectra

Derivatization is used to increase both negative‐ion sensitivity and positive‐ion sequence information in the liquid secondary‐ion mass spectra (LSIMS) of a series of peptides. The derivatization method involves acylation with pentafluorobenzyl fluoride in a single‐step reaction, and the reaction mixture is applied directly to the probe tip for analysis. Acylation takes place at the unprotexted N‐terminus, tyrosine, and lysine. The derivatives exhibit increased signal‐to‐noise ration for [MH]− ions, especially where there is not already an acidic amino acid residue in the peptide. In positive‐ion LSIMS, the N‐terminal group acts to retain the charge at the N‐terminus, simplifying the fragmentation by producing N‐terminal fragment ions. It also increases positive‐ion fragmentation, sometimes very dramatically, making sequence determination more straightforward. The simplicity of the process, together with the enhancements it provides, make3 this a generally useful method for obtaining peptide structural information.