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A MedChem toolbox for cereblon-directed PROTACs.

ABSTRACT: A modular chemistry toolbox was developed for cereblon-directed PROTACs. A variety of linkers was attached to a CRBN ligand via the 4-amino position of pomalidomide. We used linkers of different constitution to modulate physicochemical properties. We equipped one terminus of the linker with a set of functional groups, e.g. protected amines, protected carboxylic acids, alkynes, chloroalkanes, and protected alcohols, all of which are considered to be attractive for PROTAC design. We also highlight different opportunities for the expansion of the medicinal chemists' PROTAC toolbox towards heterobifunctional molecules, e.g. with biotin, fluorescent, hydrophobic and peptide tags.

SUBMITTER: Steinebach C

PROVIDER: S-EPMC6596386 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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A MedChem toolbox for cereblon-directed PROTACs.

Steinebach Christian C Sosič Izidor I Lindner Stefanie S Bricelj Aleša A Kohl Franziska F Ng Yuen Lam Dora YLD Monschke Marius M Wagner Karl G KG Krönke Jan J Gütschow Michael M

MedChemComm 20190528 6

A modular chemistry toolbox was developed for cereblon-directed PROTACs. A variety of linkers was attached to a CRBN ligand via the 4-amino position of pomalidomide. We used linkers of different constitution to modulate physicochemical properties. We equipped one terminus of the linker with a set of functional groups, e.g. protected amines, protected carboxylic acids, alkynes, chloroalkanes, and protected alcohols, all of which are considered to be attractive for PROTAC design. We ...[more]

PMID: 31304001

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