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These findings establish cooperativity, intrinsic PPI affinity, and MG affinity as key parameters governing MG activity and selectivity, providing a framework for the rational design of MGs targeting hub protein interactomes.
14-3-3 Proteins are hub proteins with an extensive interactome of phosphorylated client proteins, making them attractive targets for molecular glues (MGs) that stabilize specific 14-3-3/client protein complexes. However, selectively stabilizing individual 14-3-3 protein-protein interactions (PPIs) remains a key challen...
These hits offer amenable starting points for discovery and development of non-nucleoside inhibitors and provide opportunities for structure-based drug design against enteroviruses.
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