Investigation of isomerization mechanism of aspartic acid involved in the development of cataract

2019 Fiscal Year Final Research Report

• Project/Area Number: 16K16605
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Applied health science
• Research Institution: Tokyo University of Pharmacy and Life Science (2017-2019); International University of Health and Welfare (2016)
• Principal Investigator: Sakaue Hiroaki 東京薬科大学, 薬学部, 助教 (80734855)
• Project Period (FY): 2016-04-01 – 2020-03-31
• Keywords: D-アミノ酸 / アスパラギン酸 / 異性化 / 紫外線

Outline of Final Research Achievements

In this study, we succeeded in developing a rapid method for detecting isomerization of aspartic acid (Asp) residue and glutamic acid (Glu) residue. Aromatic amino acids such as tryptophan and tyrosine suppressed the isomerization reaction of Asp residues in peptides by ultraviolet. It was considered that the energy absorbed by the aromatic amino acids were not transferred to the isomerization reaction of Asp and was used for decomposition to protect the peptide from isomerization. On the other hand, it was also suggested that pH change and coexistence of reducing sugars promote isomerization. It was suggested that UV irradiation accelerated the isomerization of Asp indirectly.

Free Research Field

生化学

Academic Significance and Societal Importance of the Research Achievements

タンパク質中のアスパラギン酸残基の異性化は、タンパク質機能を劇的に変化させることを以前の研究により明らかにしている。白内障の発症と水晶体クリスタリン中のアスパラギン酸残基の異性化には相関があることから、アスパラギン酸残基の異性化を抑制することは白内障の予防薬や発症時期を遅らせる薬剤の開発に繋がる。本研究により、芳香族アミノ酸はアスパラギン酸残基の異性化を抑制することが明らかになった。また、還元性を有する糖やわずかなpHの変化が異性化を促進することが示唆された。本研究で得られた知見は、アスパラギン酸残基の新たな異性化促進メカニズムを考察する上で有意義なものであると言える。