Chemical Science · 2021 · 31 citations · 30 references
Life SciencesBiochemistryBiomolecular EngineeringProtein BiochemistryProtein EngineeringStructural BiologyAllosteric Protein EngineeringPost-translational Modification EngineeringProtein ChemistryProtein DesignProtein Engineering Of EnzymesProtein StructureElectrophile-protein InteractionsPrecision EngineeringReactivitySite-selective ActivationSite-selective FunctionalizationSite-specific Modification EngineeringStructure-guided Protein EngineeringTarget Site Modification
The conservation of chemoselectivity becomes invalid for multiple electrophilic warheads during protein bioconjugation. Consequently, it leads to unpredictable heterogeneous labeling of proteins. Here, we report that a linchpin can create a unique chemical space to enable site-selectivity for histidine and aspartic acid modifications overcoming the pre-requisite of chemoselectivity.
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