Development for the functional middle size molecules to the high ordered nucleic acidsstructure

2019 Fiscal Year Final Research Report

• Project Area: Middle molecular strategy: Creation of higher bio-functional molecules by integrated synthesis.
• Project/Area Number: 15H05838
• Research Category: Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
• Allocation Type: Single-year Grants
• Review Section: Science and Engineering
• 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): 鬼塚 和光 東北大学, 多元物質科学研究所, 准教授 (00707961)
• Project Period (FY): 2015-06-29 – 2020-03-31
• Keywords: 核酸高次構造 / アルキル化 / 中分子 / RNA高次構造 / グアニン４重鎖 / ノンコーディングRNA

Outline of Final Research Achievements

DNA and RNA can also adopt great varieties of stable higher-order structure motifs, such as the G-quadruplex (G4s), mismatch and bulge. Many of these secondary structures were found to be closely related to the control of the gene expression. Therefore, the higher-order structure of nucleic acids is one of the candidates for therapeutic targets. Due to the therapeutic potentials, efforts on the development of small molecule binders to specifically target the higher-order structures of nucleic acids have been intensely carried out. With the aim to augment the stabilization effect, selective alkylation using small molecules targeting the higher-order structures of nucleic acids have also been pursued. In this research we developed the new middle-size molecules with the binding group to target nucleic acids and the alkylating moiety, for alkylation to higher-order structures of nucleic acids.

Free Research Field

核酸化学　ケミカルバイオロジー

Academic Significance and Societal Importance of the Research Achievements

核酸の高次構造は、最近、特に種々の機能性RNAにおいてその機能を担うモチーフとして、重要であることがわかってきている。現在、世界を震撼させているコロナウイルスはRNAウイルスであり、構造内には高次構造を持つ。すなわちこれらのRNAの構造に結合する中分子は、RNAウイルスのRNAに結合し、ウイルスの増殖阻害に繋がる可能性がある。今回、申請者らが開発したアルキル化プローブは、特定の高次構造に結合し、反応性がONになるという非常に興味深い性質を持っており学術的意義は高い。さらに、RNAの高次構造に結合する分子も見出しており、社会的意義も非常に高いと考えている。