Synthesis and function analysis of mini-chromosome model

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22245
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 37:Biomolecular chemistry and related fields
• Research Institution: The University of Tokyo
• Principal Investigator: Okamoto Akimitsu 東京大学, 先端科学技術研究センター, 教授 (60314233)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: 化学合成 / クロマチン / DNA / ヒストン / ペプチド

Outline of Final Research Achievements

(1) Chemical synthesis of the mini-chromosome model...We have completed the synthesis of the DNA units to be connected. There are two types of DNA units, each containing the Widom601 DNA sequence, and the units have protruding ends with sequences corresponding to restriction enzymes.
(2) Chemical synthesis of functional histones in mini-chromosome models... We developed a one-pot method for connecting multiple peptides using organoruthenium catalysts that are stable in air. The organoruthenium catalyst was 50 times more active than the conventional palladium complex. Using this organoruthenium catalyst, we synthesized heterochromatin factors with site-specific post-translational modifications such as phosphorylation, ubiquitination, citrullination, and acetylation.

Free Research Field

生物有機化学

Academic Significance and Societal Importance of the Research Achievements

ミニ染色体モデルを創出する方法を確立することに意義がある。任意の配列を含む染色体構造を人工的に作ることはまだ可能になっていない。この方法が確立できれば、簡便に目的の配列や人工的な機能性修飾を含むミニ染色体モデルを獲得することが可能になり、飛躍的に染色体機能研究が進むと考えられる。また、ミニ染色体モデルを創出することにより、細胞内DNA本来の構造や反応に関わる情報を獲得できるようになる。