Sensitive detection of mutagenic DNA damages containing formyl groups and its application to biological samples

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K12344
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 63030:Chemical substance influence on environment-related
• Research Institution: Kanagawa Institute of Technology
• Principal Investigator: Takamura Takeji 神奈川工科大学, 工学部, 教授 (50342910)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: アルデヒド検出 / DNA損傷 / 蛍光プローブ

Outline of Final Research Achievements

The synthesis of BODIPY derivatives with hydroxyamino groups (8-(4-((2- (aminooxy) acetamide) methyl) phenyl) -4,4-difluoro-4-bora-3a, 4a-diaza-s-indacene) was successful. It was found that this compound reacts with deoxyribose, which is one of the DNA damages. Moreover, it reacted with 5-formylcytidine, an enzymatic oxidation product of methylated cytidine, to easily produce a fluorescent substance. On the other hand, it did not react with 8-oxo-deoxyguanosine and FAPY-dA, which are DNA oxidation damages, and was found to be a highly selective reagent.

Free Research Field

環境化学

Academic Significance and Societal Importance of the Research Achievements

DNAの損傷（または内因性の修飾）には様々な種類があるが，ホルミル基（アルデヒド基）を有するDNA損傷に関しては，LC/MS/MSなどによる分析では感度が低く，十分に分析がなされていない。そこで，遺伝毒性物質の作用等によって生じる「ホルミル基を有するDNA損傷」を高感度かつ網羅的に分析する試薬を合成した。これにより種々のDNA試料について網羅的な分析を行い，各種損傷を定量することが可能となった。