Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study
Heterobifunctional molecules have proven powerful tools to induce ligase-dependent ubiquitination of target proteins. We describe here a chemical strategy for controlling a different post-translational modification (PTM): phosphorylation. Heterobifunctional molecules were designed to promote the pro...
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| Veröffentlicht in: | Journal of medicinal chemistry 2020-03, Vol.63 (6), p.2807-2813 |
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| container_end_page | 2813 |
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| container_issue | 6 |
| container_start_page | 2807 |
| container_title | Journal of medicinal chemistry |
| container_volume | 63 |
| creator | Yamazoe, Sayumi Tom, Jeffrey Fu, Yue Wu, Wenqiong Zeng, Liang Sun, Changlei Liu, Qi Lin, Jie Lin, Kui Fairbrother, Wayne J Staben, Steven T |
| description | Heterobifunctional molecules have proven powerful tools to induce ligase-dependent ubiquitination of target proteins. We describe here a chemical strategy for controlling a different post-translational modification (PTM): phosphorylation. Heterobifunctional molecules were designed to promote the proximity of a protein phosphatase (PP1) to protein targets. The synthesized molecules induced the PP1-dependent dephosphorylation of 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. |
| doi_str_mv | 10.1021/acs.jmedchem.9b01167 |
| format | Article |
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| title | Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study |
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