28谷口 陽祐13Yosuke TANIGUCHI大庭 誠14Makoto OBADNA中の微量な損傷塩基を特異的に増幅し検出を可能にする人工核酸の合成と機能評価（2019採択）Synthesis and evaluation of artificial nucleic acids for the amplification and detection of damaged nucleobase in DNA(Project 2019)環境・刺激に応答した機能性ペプチドフォルダマーの開発（2019採択）Development of functional peptide foldamers in response to environment and stimuli(Project 2019)酸化損傷塩基の一つにグアノシンの8位が酸化された8-オキソグアノシンがある．この小さな傷が様々な疾患の発症と関連があることが知られているが，DNA中の8-オキソグアノシンの位置を特定できる手法は無い．そこで，本研究ではDNA中の8-オキソグアノシンを認識可能な人工ヌクレオチド誘導体を開発し，酵素反応を用いた発生位置特定法の開発を行った．実際に，新規のデアザプリン骨格を有する人工核酸の化学合成に成功し，一塩基伸長反応を行った結果，効率的な酵素反応には核酸塩基に窒素原子が必要であることが確認された．今後，様々な酵素を用いて一塩基伸長反応を行い有用な条件を見いだすことにより，酸化損傷塩基と疾患の詳細な関係が明らかになると期待できる．One of the damaged nucleobases is 8-oxoguanosine in which the 8-position of guanosine is oxidized. Al-though it is known that 8-oxoguanosine is associated with the various diseases, there is no method for locating in DNA. Therefore, in this study, we tried to develop an artificial nucleotide derivative that can recognize 8-oxoguanosine in DNA and tested the sequence using an enzymatic reaction. In fact, we succeeded in chemi-cally synthesizing an artificial nucleotide analogue and performed a single-nucleotide primer extension reac-tion. As a result, it was confirmed that a nitrogen atom is required for the nucleobase for an efficient enzymat-ic reaction. In the future, it is expected that the detailed relationship between oxidatively damaged bases and diseases will be clarified by performing a single-nucleotide primer extension reaction using various enzymes.本研究では，タンパク質とオリゴペプチドがもつ長所を兼ね備えた機能性ペプチドフォルダマー（フォルダマー：低分子を並べてオリゴマーにすると一定の二次構造をとる分子）の創製を目的とする．すなわち，短鎖でペプチド二次構造を固定化し，環境・刺激に応答してペプチドの立体構造を変化させる非天然型アミノ酸を開発する．実際に，側鎖にボロン酸，もしくは二級アミンを有する環状ジ置換アミノ酸を設計・合成し，その含有ペプチドの二次構造解析を行ったところ，環境に応答して二次構造が変化することが明らかとなった．また，天然のアミノ酸から構成させるペプチド中に様々な側鎖構造を有するジ置換アミノ酸を導入したところ，二次構造は大きく異なっており，その二次構造が機能に寄与することが示唆された．The purpose of this study is to develop functional peptide foldamers (foldamers: folded oligomers with a well-defined conformation) that have the advantages of proteins and oligopeptides. We developed unnatural amino acids, which stabilized a peptide secondary structure with a short sequence and changed the conforma-tion of the peptides in response to the environment and stimuli. In fact, we designed and synthesized cyclic disubstituted amino acids (dAAs) having boronic acid or a secondary amine in the side chain and analyzed the secondary structures of peptides containing their dAAs. In consequence, we revealed that the peptide sec-ondary structures changed in response to the environment. In addition, when dAAs having various side chain structures were introduced into peptides composed of natural amino acids, their secondary structures were significantly different, suggesting that the secondary structures would contribute to their functions.
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