2026-11-05 スイス連邦工科大学ローザンヌ校(EPFL)

Secondary serotonin aptamer (green) binds to the target-bound primary serotonin aptamer (pink). 2026 EPFL CHEMINA CC BY SA
<関連情報>
- https://actu.epfl.ch/news/a-new-sensing-architecture-to-detect-small-molec-2/
- https://www.nature.com/articles/s41557-026-02286-4
アプタマーは、独特な立体構造DNA認識様式を可能にする Aptamers enable a distinct mode of conformational DNA recognition
Annina Stuber, Kyungae Yang, Sandra Hernández Escobar, Antoine Cléry, Ali Douaki, Núria Moretó Bravo, Diego Lamm, Vlastimil Jirasko, Frédéric H.-T. Allain, Denis Garoli & Nako Nakatsuka
Nature Chemistry Published:05 November 2026
DOI:https://doi.org/10.1038/s41557-026-02286-4
Abstract
Watson–Crick base-pairing defines the classical paradigm of nucleic-acid interactions, but growing research reveals noncanonical modes beyond this framework. Here we uncover a mode of interactions by which two DNA strands associate through a ligand-induced conformational rearrangement. Upon binding a small molecule, a structure-switching primary aptamer folds into a conformation that exposes a previously inaccessible docking interface. An independently evolved secondary aptamer recognizes this interface primarily through noncanonical interactions rather than sequence complementarity, reporting the ligand-bound state of the primary aptamer. This interaction is conformation-sensitive: single base-pair changes in the primary aptamer modulate secondary aptamer recognition. Across four chemically distinct small-molecule targets—serotonin, dopamine, testosterone and deoxycorticosterone 21-glucoside—secondary aptamers were identified for three, and the serotonin system was translated into surface-based sandwich assays. These results demonstrate that a ligand-induced conformational state, rather than sequence complementarity or the chemical identity of the ligand, can serve as the epitope for nucleic-acid recognition, expanding the molecular features that DNA can be evolved to detect.

