Analyses of chemical modifications on proteins and peptides by mass spectrometry: Efficient biomarker discoveries for diagnostic and therapeutic purposes

Proteins and peptides are exposed to higher chemical stresses during some physiological events such as increased oxidative stress from degenerative aging diseases. Therefore, the resulting chemical modifications can provide significant information about biological events. Chemically modified abundant proteins have been analyzed by mass spectrometry, mainly for use as dosimeters of chemical exposure. However, quantitative analyses of bioactive peptides and proteins in specific diseases have relied almost exclusively on the use of immunoassay-based procedures with no concern for possible chemical modifications. Therefore, important information could be overlooked, or considerable misunderstandings could be created, if the modifications are not distinguished and if they alter protein functions such as phosphorylation. I believe that chemical modifications on proteins and peptides could play important roles, not only as diagnostic and therapeutic markers, but also as triggers that initiate some diseases. In this article, I first introduce my previous researches related to oxidative stress, such as chemi-cally modified histone, hemoglobin, amyloid /? by reac-tive oxygen species and 4-oxo-2 (E) -nonenal derived from lipid peroxides. As the future perspective, I then describe a novel "omics" strategy for efficient bio-marker discovery using chemical modifications on bioactive peptides.