RNAとDNAの組み合わせにより核酸アプタマーの分子認識を調節できることを発見—分子標的薬やバイオセンサ開発に向けた核酸材料設計の分子基盤を確立—

2025-05-15 千葉工業大学

図１　バイオセンサ（アプタマーセンサ）のイメージ

＜関連情報＞

• https://www.soumunomori.com/pressrelease/detail/pr-147126/
• https://pubs.acs.org/doi/10.1021/acschembio.6c00034

ヌクレオチドの柔軟性がアプタマー-タンパク質認識に及ぼす影響：RNAとRNA-DNAキメラの比較 Impact of Nucleotide Flexibility on Aptamer–Protein Recognition: RNA vs RNA–DNA Chimera

Takuya Hasegawa,Tomoki Sakamoto,Masahiro Sekiguchi,Masataka Horiuchi,Takeshi Ishikawa,Masato Katahira,Takashi Nagata,Kenji Yamagishi,and Taiichi Sakamoto
ACS Chemical Biology  Published: April 17, 2026
DOI:https://doi.org/10.1021/acschembio.6c00034

Abstract

Aptamers are single-stranded nucleic acid molecules that bind specifically and strongly to target molecules by adopting a unique tertiary structure that fits the target molecule. They have a wide range of biomedical applications, including disease treatment and diagnosis. Two types of aptamers exist: DNA aptamers and RNA aptamers. The only aptamers currently approved as therapeutic agents are chemically modified RNA aptamers, although DNA aptamers are inherently more nuclease-resistant than RNA aptamers. An RNA aptamer that binds to the Fc fragment of IgG1 and an RNA–DNA chimeric aptamer in which approximately half of the RNA is replaced by DNA have previously been reported, but their binding mechanisms have not yet been compared. In this study, we compared the binding mechanisms of these aptamers to the Fc fragment using isothermal titration calorimetry, nuclear magnetic resonance spectroscopy, and molecular dynamics simulations. Although the RNA and chimeric aptamers exhibited similar binding affinities for the Fc fragment, the chimeric aptamer appeared to be more flexible than the RNA aptamer and to achieve a better fit to the Fc fragment, resulting in a larger enthalpy change. However, the flexibility of the chimeric aptamer led to a large entropy loss during interaction with the Fc fragment, which was compensated for by the large enthalpy change. Overall, these findings highlight a trade-off between flexibility-driven enthalpic gain and entropic cost, providing mechanistic insights into aptamer–protein recognition and a basis for rational aptamer design.