Radosław Nowak

Jul 28, 2024 | nature.com | Moritz Hunkeler |Mingxing Teng |Justine C. Rutter |Anna M Schmoker |Rebecca Metivier |Woong Sub Byun | +9 more

AbstractMolecular glues are proximity-inducing small molecules that have emerged as an attractive therapeutic approach. However, developing molecular glues remains challenging, requiring innovative mechanistic strategies to stabilize neoprotein interfaces and expedite discovery. Here we unveil a trans-labeling covalent molecular glue mechanism, termed ‘template-assisted covalent modification’.

Apr 28, 2024 | nature.com | Radosław Nowak |Benjamin Ebert

AbstractTargeted protein degradation refers to the use of small molecules to induce the selective degradation of proteins. In its most common form, this degradation is achieved through ligand-mediated neo-interactions between ubiquitin E3 ligases — the principal waste disposal machines of a cell — and the protein targets of interest, resulting in ubiquitylation and subsequent proteasomal degradation.