Strategies for identification of covalent xenobiotic modifications in proteins by mass spectrometry

The structural elucidation of covalent xenobiotic modifications in proteins is a powerful approach to identify compounds that may be responsible for genotoxic damage in humans. Many proteins, such as hemoglobin can be readily obtained in relatively large quantities. Since covalent modifications in proteins are not repaired, xenobiotic damage can accumulate over the lifetime of the protein and reveal exposure over extended time periods. Recently developed mass spectrometric methods are ideally suited to tackling protein structural problems involving covalent modifications. A variety of strategies to identify xenobiotic covalent modifications in proteins using mass spectrometry are discussed.