Development of the strategy for the site-directed modification in hydrophobic pocket of DNA for the control of gene expression

2015 Fiscal Year Final Research Report

• Project/Area Number: 25288073
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Bio-related chemistry
• Research Institution: Tohoku University
• Principal Investigator: Nagatsugi Fumi 東北大学, 多元物質科学研究所, 教授 (90208025)
• Co-Investigator(Kenkyū-buntansha): YAMADA Ken 東北大学, 多元物質科学研究所, 助教 (70736074)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: アルキル化反応 / 塩基欠損部位 / 疎水空間 / 核酸高次構造 / クリックケミストリー / 蛍光標識

Outline of Final Research Achievements

Alkylation to DNA is one of the mechanisms on the anticancer drug. Some of the alkylating agents, for example, cisplatin, melphalan etc., are used as the anticancer drugs for clinical application. But these drugs did not have the selectivity to target genes, resulted in the serious side effects. The alkylated reactions with high selectivity to target genes have the potential for developing the new anticancer drugs without side effects. In our research, we attempted the development the site directed alkylation activated with proximity effects to a target base in the hydrophobic space. We designed the new alkylated probes activated by hydrogen bonding formation to a target base in hydrophobic space. These probes consisted of alkylating part, 2-amino-6-vinylpurine, and binding part, Hoechst, exhibited high selectivity to thymine. These probes are expected to apply for the new tool as a selective control of gene expression

Free Research Field

核酸化学、ケミカルバイオロジー