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Related Experiment Video

Updated: May 8, 2026

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
07:22

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)

Published on: January 12, 2024

A new 4-atom linker enables PROTAC development and imaging.

Spyros Letsios1,2, Giovana Carrasco2, Martin Lee2

  • 1EaStChem School of Chemistry, University of Edinburgh Edinburgh EH9 3FJ UK Alison.Hulme@ed.ac.uk.

RSC Chemical Biology
|May 7, 2026
PubMed
Summary
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Accelerating fragment-based drug discovery using grand canonical nonequilibrium candidate Monte Carlo.

Nature communications·2025

New Proteolysis Targeting Chimeras (PROTACs) utilize short diyne linkers for potent BRD4 degradation. This design also allows label-free tracking of PROTACs inside cells using advanced microscopy.

Area of Science:

  • Medicinal Chemistry
  • Chemical Biology
  • Molecular Pharmacology

Background:

  • Proteolysis Targeting Chimeras (PROTACs) are an emerging drug class.
  • Linker design is critical for PROTAC efficacy and properties.
  • Shorter, rigid linkers are often preferred in PROTAC design.

Purpose of the Study:

  • To investigate the potential of short diyne spacers as PROTAC linkers.
  • To develop novel, potent PROTACs for BRD4 degradation.
  • To explore the use of diyne moieties for visualizing PROTAC cellular uptake.

Main Methods:

  • Synthesis of diyne-containing PROTACs targeting BRD4.
  • Evaluation of PROTACs' degradation activity against the CRL4CRBN E3 ligase complex.
  • Utilisation of stimulated Raman scattering (SRS) microscopy for label-free cellular imaging.

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Active Probe Atomic Force Microscopy with Quattro-Parallel Cantilever Arrays for High-Throughput Large-Scale Sample Inspection
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Active Probe Atomic Force Microscopy with Quattro-Parallel Cantilever Arrays for High-Throughput Large-Scale Sample Inspection

Published on: June 13, 2023

Related Experiment Videos

Last Updated: May 8, 2026

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)
07:22

The Development and Application of Biophysical Assays for Evaluating Ternary Complex Formation Induced by Proteolysis Targeting Chimeras (PROTACS)

Published on: January 12, 2024

Active Probe Atomic Force Microscopy with Quattro-Parallel Cantilever Arrays for High-Throughput Large-Scale Sample Inspection
05:04

Active Probe Atomic Force Microscopy with Quattro-Parallel Cantilever Arrays for High-Throughput Large-Scale Sample Inspection

Published on: June 13, 2023

Main Results:

  • Developed low nanomolar BRD4 degraders using diyne-based PROTACs.
  • Demonstrated that the Raman-active diyne moiety enables label-free visualization of PROTAC uptake.
  • Achieved intracellular drug visualization at low micromolar concentrations via SRS microscopy.

Conclusions:

  • Diyne-based PROTAC linkers can yield highly potent degraders.
  • The diyne moiety offers a novel tool for studying PROTAC cellular dynamics.
  • This approach addresses challenges in understanding PROTAC intracellular localization and uptake mechanisms.