EVALUATION OF MALDI-FTMS FOR ANALYSIS OF PEPTIDE MIXTURES GENERATED BY LADDER SEQUENCING

Matrix-assisted laser desorption/ionization Fourier transform mass spe ctrometry (MALDI-FTMS) is evaluated as an alternative to MALDI time-of -flight mass spectrometry (TOF-MS) for analysis of ladder-generated pe ptide mixtures because FTMS can provide high resolution and mass accur acy. Analysis of ladder sequences of high-mass peptides (above 3000 Da ) by MALDI-FTMS is difficult because the terminating agent used in ''l adder-generating chemistry'' is unstable on the time scale of MALDI-FT MS experiments. However, ladder sequences of low-mass peptide mixtures can be successfully analyzed by MALDI-FTMS. It is shown that for pept ides less than 1500 Da, MALDI-FTMS permits an average mass error of on ly +/- 0.008 Da for identifying amino acids. Thus, ladder sequencing b y FTMS has significant potential, particularly if more stable terminat ing groups can be identified. (C) 1997 Elsevier Science B.V.