Compounds and methods for DCAF-mediated protein degradation
AssigneeThe Scripps Research Institute
InventorsBenjamin Cravatt, Vincent Crowley, Xiaoyu Zhang
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Abstract
Disclosed herein are methods and compounds for inducing DDB1- and CUL4-associated factor 16 (DCAF16)-mediated protein degradation in mammalian cells. In some embodiments, also disclosed herein are methods of modulating the substrate selectivity of a DCAF16-CUL4-RBX1-DDB1 complex (CRL4) for modulating protein degradation.
Claims17
A DDB1- and CUL4-associated factor 16 (DCAF16) conjugate comprising a DCAF16 protein covalently bound to a synthetic ligand at a cysteine residue, wherein the cysteine residue is at an amino acid position corresponding to residue 58, 100, 103, 119, 173, 177, 178, or 179 of the amino acid sequence of SEQ ID NO:
- 1, and wherein the synthetic ligand comprises the structure of Formula (I):
- wherein,
- CRG is a bromodomain binder;
- L is a linker;
- MRE is a molecular recognition element that is capable of interacting with DCAF16, wherein the MRE comprises a Michael acceptor moiety capable of forming a covalent bond to the thiol of a cysteine residue in the DCAF16 protein;
- and RM comprises a binding element that binds to a second protein or another compound.
Dependencies are inferred from the claim text.