Nucleic Acid-to-Small Molecule Converter through Amplified Hairpin DNA Circuits.


Journal

Angewandte Chemie (International ed. in English)
ISSN: 1521-3773
Titre abrégé: Angew Chem Int Ed Engl
Pays: Germany
ID NLM: 0370543

Informations de publication

Date de publication:
26 10 2023
Historique:
received: 10 05 2023
medline: 23 10 2023
pubmed: 14 9 2023
entrez: 13 9 2023
Statut: ppublish

Résumé

Many microRNAs (miRNAs) are characteristically found in cancer cells, making miRNAs promising marker biomolecules for cancer diagnosis and therapeutics. However, it is challenging to use miRNA as a cancer signature because it is difficult to convert the nucleic acid sequence information into molecular functionality. To address this challenge, we realize nucleic acid-to-small molecule converters using hairpin DNA circuits. Harnessing a Staudinger reduction as a trigger for the conversion, we constructed hybridization chain reaction (HCR) and catalytic hairpin assembly (CHA) circuits that respond to oncogenic miR-21. Fluorophore and dye molecules were released in response to miR-21 through the HCR, providing fluorogenic and chromogenic readouts. Selective cytotoxicity in miR-21-abundant cells was realized by the CHA to release the anticancer drug SN-38. This would be the first example of selective activation of a small-molecule prodrug triggered by oncogenic miRNA in human living cells.

Identifiants

pubmed: 37704581
doi: 10.1002/anie.202306587
doi:

Substances chimiques

Nucleic Acids 0
DNA 9007-49-2
MicroRNAs 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e202306587

Informations de copyright

© 2023 The Authors. Angewandte Chemie International Edition published by Wiley-VCH GmbH.

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Auteurs

Kunihiko Morihiro (K)

Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Yasuhiro Tomida (Y)

Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Daisuke Fukui (D)

Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Manami Hasegawa (M)

Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

Akimitsu Okamoto (A)

Department of Chemistry and Biotechnology, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8656, Japan.

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