English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

Chemical Ligand Space of Cereblon

MPS-Authors
/persons/resource/persons273348

Boichenko,  I
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Conservation of Protein Structure and Function Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons273352

Bär,  K
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons273356

Deiss,  S
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Conservation of Protein Structure and Function Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271516

Heim,  C
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons77670

Albrecht,  R
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons78342

Lupas,  AN
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271242

Hernandez Alvarez,  B
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Conservation of Protein Structure and Function Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

/persons/resource/persons271510

Hartmann,  MD
Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;
Molecular Recognition and Catalysis Group, Department Protein Evolution, Max Planck Institute for Developmental Biology, Max Planck Society;

External Resource
No external resources are shared
Fulltext (restricted access)
There are currently no full texts shared for your IP range.
Fulltext (public)
There are no public fulltexts stored in PuRe
Supplementary Material (public)
There is no public supplementary material available
Citation

Boichenko, I., Bär, K., Deiss, S., Heim, C., Albrecht, R., Lupas, A., et al. (2018). Chemical Ligand Space of Cereblon. ACS Omega, 3(9), 11163-11171. doi:10.1021/acsomega.8b00959.


Cite as: https://hdl.handle.net/21.11116/0000-000A-6681-1
Abstract
The protein cereblon serves as a substrate receptor of a ubiquitin ligase complex that can be tuned toward different target proteins by cereblon-binding agents. This approach to targeted protein degradation is exploited in different clinical settings and has sparked the development of a growing number of thalidomide derivatives. Here, we probe the chemical space of cereblon binding beyond such derivatives and work out a simple set of chemical requirements, delineating the metaclass of cereblon effectors. We report co-crystal structures for a diverse set of compounds, including commonly used pharmaceuticals, but also find that already minimalistic cereblon-binding moieties might exert teratogenic effects in zebrafish. Our results may guide the design of a post-thalidomide generation of therapeutic cereblon effectors and provide a framework for the circumvention of unintended cereblon binding by negative design for future pharmaceuticals.