生体高分子の微小変化を通して見る生命現象 ―バイオマーカー探索のブレークスルーになりうるか？―

Abstract

Biological macromolecules, such as deoxyribonucleic acid (DNA) and proteins, are exposed to higher chemical stresses during some physiological events such as increased oxidative stress from degenerative aging diseases and higher glucose stress in diabetes mellitus. Therefore, the resulting chemical modifications can provide significant information about biological events. Chemically modified DNA and 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 minute 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 biological macromolecules 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 research on biomarkers such as DNA adducts and chemically modified proteins. I then present a novel “omics” strategy for biomarker discovery using minute chemical modifications on biological macromolecules.