Targeted protein degradation via intramolecular bivalent glues. (https://pubmed.ncbi.nlm.nih.gov/38383787/)

These scientists wanted to figure out how to get rid of certain proteins in our cells that can cause problems. They used a special method called targeted protein degradation. This method involves bringing together a protein that marks the target protein for destruction and the target protein itself. The scientists created a new type of compound that can stick to two parts of the target protein at the same time, making it easier for the marking protein to find and destroy it.

By studying how these compounds work at a very detailed level, the scientists discovered that instead of connecting the marking protein and the target protein separately, this new compound connects two parts of the target protein itself. This helps the marking protein to attach to the target protein more effectively, leading to its breakdown and removal from the cell.

Based on their findings, the scientists were able to design even better compounds that can destroy the target protein more efficiently. This study introduces a new way to get rid of harmful proteins in our cells by bringing different parts of the target protein together, making it easier for the marking protein to do its job.

Hsia O., Hinterndorfer M., Cowan AD., Iso K., Ishida T., Sundaramoorthy R., Nakasone MA., Imrichova H., Schatz C., Rukavina A., Husnjak K., Wegner M., Correa-Saez A., Craigon C., Casement R., Maniaci C., Testa A., Kaulich M., Dikic I., Winter GE., Ciulli A. Targeted protein degradation via intramolecular bivalent glues. Nature. 2024 Feb 21. doi: 10.1038/s41586-024-07089-6.