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Towards Covalent Fluorescent Light-Up Aptamers (coFLAPs).

Martin Bitsche1, Malou Hanisch2, Alexandra Lusser3

  • 1Department of Organic Chemistry, University of Innsbruck, AUT-6020 Innsbruck, Austria. martin.bitsche@uibk.ac.at.

Chimia
|March 28, 2026
PubMed
Summary

Researchers developed coFLAPs, a novel covalent fluorogen-activating RNA system, enhancing cellular RNA imaging. This breakthrough offers new strategies for RNA labeling, drug targeting, and covalent drug design.

Keywords:
Covalent RNA labelingFluorescent RNA (FR)Fluorogen-activating aptamersFluorophore synthesis

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Area of Science:

  • Biochemistry
  • Molecular Biology
  • Chemical Biology

Background:

  • Fluorogen-activating aptamers (FLAPs) revolutionized cellular RNA imaging, offering alternatives to green fluorescent protein (GFP).
  • Existing FLAPs utilize noncovalent fluorogen-RNA interactions, contrasting with GFP's covalent fluorophore integration.
  • Over ten FLAP systems have been developed, spanning a wide spectral range.

Purpose of the Study:

  • To introduce and discuss recently developed FLAPs, focusing on the first covalent FLAP (coPepper).
  • To highlight coPepper as a strategy to overcome current limitations in FLAP-based RNA imaging.
  • To explore the impact of bioconjugation chemistry developed for coFLAPs on RNA labeling and drug design.

Main Methods:

  • Review of recently developed FLAP systems, including covalent variants.
  • Discussion of the principles and applications of coPepper, the first covalent FLAP.
  • Analysis of bioconjugation chemistry for covalent RNA labeling and drug targeting.

Main Results:

  • The development of coPepper represents a significant advancement in FLAP technology.
  • Covalent FLAPs offer a new strategy to address limitations in current RNA imaging techniques.
  • The associated bioconjugation chemistry has broad implications for RNA labeling and covalent drug design.

Conclusions:

  • Covalent FLAPs, exemplified by coPepper, present a promising new direction for RNA imaging.
  • The bioconjugation chemistry for coFLAPs extends beyond RNA imaging, impacting drug development.
  • This work paves the way for improved RNA targeting and covalent drug design strategies.