Issue 40, 2025

A structural reorganization-based catalytic hairpin assembly enabling small-molecule monitoring in living cells

Abstract

Small-molecule drugs, constituting over 60% of FDA-approved therapeutics (2017–2022), present unresolved challenges relating to elucidating their intracellular mechanisms. We present a dual-strategy platform integrating “in silico aptamer affinity maturation” (ISAAM) and “structural reorganization-catalytic hairpin assembly” (SR-CHA). ISAAM computationally designs high-affinity aptamers, while SR-CHA eliminates undesired signals via energy-minimized conformational control, achieving a signal-to-background improvement over conventional CHA. This system enables ultrasensitive small-molecule monitoring in live cells, resolving traditional challenges of false positives and inefficiency. Demonstrated through intracellular imaging and kinetic studies, SR-CHA offers a robust tool for probing small-molecule interactions in biological systems, advancing drug discovery and diagnostic applications.

Graphical abstract: A structural reorganization-based catalytic hairpin assembly enabling small-molecule monitoring in living cells

Supplementary files

Article information

Article type
Edge Article
Submitted
24 Jun 2025
Accepted
28 Aug 2025
First published
30 Aug 2025
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY-NC license

Chem. Sci., 2025,16, 18739-18747

A structural reorganization-based catalytic hairpin assembly enabling small-molecule monitoring in living cells

R. Wang, W. Yang, M. Su, J. Qin, J. Liu, X. Yang, J. Cao, R. Yuan, Y. Zhuo, M. Chen, C. Yang and W. Liang, Chem. Sci., 2025, 16, 18739 DOI: 10.1039/D5SC04624F

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