Mapping Reagent Space for Fragment Ion Mass Defect Labeling (FIMDL) of Peptides

摘要

Peptide labeling is an important sample preparation method in mass spectrometry-based proteome analysis. Modification of peptide termini has been extensively explored, enabling global analysis of proteome digests. However, mass spectrometric analysis of modified peptides and their fragments is hindered by native peptide ions and chemical noise. The exact mass of a peptide differs characteristically from its nominal mass by a value called the mass defect. Limited by possible elemental compositions, the mass defect of peptides has a restricted range, resulting in an unoccupied mass spectral space in every mass-to-charge range, known as the forbidden zone. The method of fragment ion mass defect labeling (FIMDL) places characteristic fragment ions of modified peptides into unused spectral space where no native peptide fragment ions exist. In this labeling method, peptides are chemically modified in solution and the modified peptides, upon gas-phase collision in a mass spectrometer, generate fragment ions with significantly shifted mass defects. This work is a survey of a variety of chemical reagents possessing a halogen-substituted phenyl moiety, to shift the fragment masses into occupied mass spectral regions. This survey aims to identify candidate compounds and more importantly underline principles for further development of new FIMDL reagents.