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Related Experiment Video

Updated: Feb 14, 2026

Preparation of Stable Bicyclic Aziridinium Ions and Their Ring-Opening for the Synthesis of Azaheterocycles
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Utilizing Constrained Bicyclic Peptides for In Vitro Diagnostics.

André Shamsabadi1, Adam Creamer1, Christy J Sadler1

  • 1Department of Materials, Department of Bioengineering and Institute of Biomedical Engineering, Imperial College London, London SW7 2AZ, U.K.

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Summary

Bicyclic peptides, or Bicycle molecules, show promise for diagnostics. Researchers developed sensitive SARS-CoV-2 nucleocapsid protein detection assays using these molecules, paving the way for new biosensor technologies.

Keywords:
ELISALFIAantibody mimicbicyclic peptidesdiagnostics

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Area of Science:

  • Biochemistry
  • Biotechnology
  • Molecular Diagnostics

Background:

  • Constrained bicyclic peptides (Bicycle molecules) offer high affinity for biological targets and are explored as therapeutic agents.
  • Their potential in diagnostic immunoassays, mimicking antibody functions, remains largely uninvestigated.
  • These synthetic scaffolds allow for easy modification and scalable production.

Purpose of the Study:

  • To explore the utility of Bicycle molecules in diagnostic immunoassays.
  • To develop sensitive detection methods for SARS-CoV-2 nucleocapsid (N) protein using Bicycle molecules.
  • To evaluate Bicycle molecules as biorecognition elements in various immunoassay formats.

Main Methods:

  • Phage display screening was employed to identify Bicycle molecules targeting SARS-CoV-2 N protein constructs.
  • Identified Bicycle molecules were assessed for binding affinities.
  • Validated Bicycle molecules in the development of enzyme-linked immunosorbent assays (ELISA), nanozyme-linked immunosorbent assays (NA-ELISA), and lateral flow immunoassays (LFIA).

Main Results:

  • Several Bicycle molecules with binding affinities from micromolar to low nanomolar ranges were identified against SARS-CoV-2 N protein.
  • These molecules were successfully integrated into various immunoassay platforms, including ELISA, NA-ELISA, and LFIA.
  • The developed assays demonstrated the capability for detecting ultralow concentrations of SARS-CoV-2 N protein.

Conclusions:

  • Bicycle molecules are effective biorecognition scaffolds for developing ultrasensitive diagnostic immunoassays.
  • Their synthetic accessibility and high binding affinity facilitate robust, cost-effective, and large-scale biosensor development.
  • This work opens avenues for utilizing Bicycle molecules in detecting diverse biomarkers beyond viral proteins.