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New method measures binding of molecules to pharmacological targets

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18 April 2023
Medicinal chemists at VU Amsterdam have developed a novel technology, in collaboration with University of Nottingham and Dutch antibody company QVQ, to easily assess the binding of ligands, a type of binding molecules, to different drug targets in real time. The coupling of this technology, named NanoB2 (nanobody-NanoBRET), with other binding assays could increase our understanding of ligand pharmacology. In addition, this technology could aid drug development.

A ligand is a molecule that binds to a receptor, which as a consequence influence various biological processes in a highly targeted manner. Intervention in such processes is a key attribute of the mechanism of action of many medicines. Since the therapeutic potential of drugs depends on how they interact with their targets, it is important to assess and optimize the binding between ligands and receptors early in the drug development process. VU Amsterdam PhD students Jelle van den Bor and Nick Bergkamp therefore developed, under the guidance of Raimond Heukers and professor Martine Smit, a technology that combines nanobodies with nanoluciferase-based bioluminescence resonance energy transfer (NanoBRET) to assess this binding. The results have been published in Cell Report Methods.

The biophysical technique NanoBRET is emerging as a powerful tool to detect the proximity or interaction of proteins. Large-scale use of NanoBRET has however been hampered by technical challenges in obtaining fluorescently labeled ligands, such as small molecules. Because the newly developed NanoB2 technology uses specific proteins (antibodies or fragments thereof) as carrier of the fluorescent probes, quantitative ligand pharmacology became applicable for a wider range ligands. Although the technology depends on the availability or development of such antibodies, it has the potential to measure the binding of all types of ligands, biological or chemical.

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