Themed collection Molecular Glues
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Bringing enzymes to the proximity party
Targeted enzymes can drive cell type-selective reactions that are not yet possible with other therapeutic approaches.
RSC Chem. Biol., 2023,4, 986-1002
https://doi.org/10.1039/D3CB00084B
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Protein–protein interfaces in molecular glue-induced ternary complexes: classification, characterization, and prediction
This review surveys molecular glue-induced ternary complexes in the PDB and provides an overview of computational methods that can be utilized to predict them.
RSC Chem. Biol., 2023,4, 192-215
https://doi.org/10.1039/D2CB00207H
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Bind&Bite: covalently stabilized heterodimeric coiled-coil peptides for the site-selective, cysteine-free chemical modification of proteins
A pair of heterodimeric coiled-coil peptides was modified to enable covalent stabilization of the dimer without using enzymes or cysteine. Fusion of the peptides to a protein and a chemical moiety, respectively, facilitates site-selective protein modification.
RSC Chem. Biol., 2023,4, 794-803
https://doi.org/10.1039/D3CB00122A
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A model-informed method to retrieve intrinsic from apparent cooperativity and project cellular target occupancy for ternary complex-forming compounds
Estimating intrinsic from apparent cooperativities to calculate concentrations of ternary complexes in biochemical and cellular assays.
RSC Chem. Biol., 2023,4, 512-523
https://doi.org/10.1039/D2CB00216G
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Straightforward model construction and analysis of multicomponent biomolecular systems in equilibrium
A framework for equilibrium models, such as molecular glues and other contemporary biomolecular multicomponent systems, is presented that automatically generates custom mass-balance models based on the reversible reactions of each system.
RSC Chem. Biol., 2023,4, 252-260
https://doi.org/10.1039/D2CB00211F
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Accessing three-branched high-affinity cereblon ligands for molecular glue and protein degrader design
The Petasis borono-Mannich reaction was employed for an entry towards three-branched cereblon ligands. The high-affinity ligands were used to assemble molecular glues and proteolysis targeting chimeras (PROTACs) targeting BRD4 for degradation.
RSC Chem. Biol., 2023,4, 229-234
https://doi.org/10.1039/D2CB00223J
About this collection
This themed collection, guest edited by Michelle Arkin (University of California San Francisco, USA), Luc Brunsveld (TU Eindhoven, Netherlands), and Eric Fischer (Dana-Farber Cancer Institute and Harvard Medical School, USA), encompasses the wide scope of molecular glues. Topics include protein degradation glues, protein binders and stabilizers, bi-functional molecules for protein degradation and beyond with a particular interest on molecular recognition.