Molecular glues are small molecules that can bind to two or more proteins, facilitating their interaction and potentially leading to the formation of protein complexes that can modulate cellular pathways.
In drug discovery, there are several experiments that can be used to design and optimize molecular glues:
🔬 Protein-protein interaction assays: These assays can help to identify candidate proteins that can be targeted with molecular glues. For example, we can use co-immunoprecipitation assays to identify proteins that interact with each other and could potentially be targeted with a molecular glue.
👩🔬 Screening assays: Once candidate protein pairs have been identified, high-throughput screening assays can be used to identify small molecules that can bind to both proteins and potentially act as a molecular glue. These assays can include fluorescence-based binding assays or surface plasmon resonance (SPR) assays.
🧬 Structural biology: Understanding the three-dimensional structure of the target proteins and how they interact with each other can help in the design of molecular glues. Techniques such as X-ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and cryo-electron microscopy can provide valuable insights into protein-protein interactions.
🦠 Cellular assays: After identifying potential molecular glue candidates, we can test their ability to modulate cellular pathways in cellular assays. For example, you can measure changes in protein-protein interactions, changes in gene expression, or changes in cellular phenotype.
At Arctoris, we bring together expert teams from biochemistry, biophysics, cellular and structural biology to answer these questions and drive #drugdiscovery with unprecedented speed and quality.