Scientists from Harvard University and Massachusetts General Hospital are pioneering an approach to fight cancer and other diseases using a novel class of ligands called cyclimids. Their distinct properties allow them to target malfunctioning proteins right at their molecular roots, offering a promising solution to prevent the uncontrolled growth of cells that leads to cancer.
Christina Woo, a senior co-author and professor of chemistry, and her team spent over a year researching cereblon—a protein that plays a crucial role in removing malfunctioning proteins. They investigated the natural ligands that cereblon recognizes to hijack it for protein degradation. Cyclimids bind to disease-causing proteins and, through their “warhead” properties, guide cereblon to mark these proteins for disposal via the cellular recycling system, the proteasome.
The research team’s findings, published in Cell: Chemical Biology, highlighted that even small changes to the cereblon ligand could significantly impact its activity in cells. Working with the Mazitschek Lab, they developed a powerful biochemical approach for predicting how effectively cyclimids can degrade proteins. This technique streamlines the identification of potential drug candidates.
Ralph Mazitschek, co-senior author, emphasized that their method provides a comprehensive and adaptable profiling platform for any molecular degrader. Their collaborative research offers the scientific community a powerful tool to accelerate the development of targeted cancer therapies.
Looking ahead, Woo and Mazitschek are optimistic that their screening method will become integral to future protein degradation strategies. This could lead to more selective and effective drug candidates, unlocking numerous opportunities for innovative treatments and transforming how researchers tackle cancer and other diseases at the molecular level.
Read More: https://news.harvard.edu/gazette/story/2024/04/a-molecular-warhead-against-disease/
