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Heterobifunctional Molecules Induce Dephosphorylation of Kinases - a Proof of Concept Study

preprint
submitted on 30.07.2019 and posted on 31.07.2019 by Sayumi Yamazoe, Steve Staben
Previous work has shown that heterodimeric molecules, in some instances referred to as PROteolysis Targeting Chimeras, promote proximity of an E3-ligase to a target of interest to induce target ubiquitination. We hypothesize that many other PTMs, beyond ubiquitination, can be catalyzed in a similar matter. This work utilizes recruitment of PP1 (protein phosphatase 1) to induce de phosphorylation of target proteins (AKT and EGFR). To our knowledge, this work represents the first examples of small molecules recruiting non-native partners to induce removal of a PTM.

History

Email Address of Submitting Author

stevents@gene.com

Institution

Genentech, Inc.

Country

United States

ORCID For Submitting Author

0000-0002-6137-6517

Declaration of Conflict of Interest

Employee of Roche and owner of Roche stock

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