Personalized molecular glue complexes with desired properties
Technology tamfitronics
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Protein engineering
Nature Biotechnology volume42,web page 571 (2024)Cite this article
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Degron tags can feature off swiftly and temporally controlled degradation of proteins the utilization of tiny molecules identified as molecular glues. These molecular glues induce or stabilize protein interactions between a aim protein and a ubiquitin ligase. As examine instruments, molecular glue complexes are restricted by the powerful size of degron tags, which prevents integration in endogenous protein-coding genes. In a ogle printed in ScienceMercer et al. apply a gentle evolution solution to generate molecular glue complexes with high affinities and smaller size, obtaining a compact degron that triggers protein degradation and not using a detectable off-aim results.
Unusual work developed an optimized molecular glue, PT-179, that binds cereblon to feature off protein degradation. Unlike its predecessors, PT-179 does now not degrade off-aim proteins, making it an supreme starting up block to get molecular glue complexes with improved properties.
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Marchal, I. Personalized molecular glue complexes with desired properties. Nat Biotechnol 42571 (2024). https://doi.org/10.1038/s41587-024-02212-4
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DOI: https://doi.org/10.1038/s41587-024-02212-4