Functional Disruption of Gli1-DNA Recognition via a Cobalt(III) Complex.
| Autor: | Brue CR; Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, IL, 60208-3113, USA., Dukes MW; Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, IL, 60208-3113, USA., Masotti M; Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, IL, 60208-3113, USA., Holmgren R; Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, IL, 60208-3113, USA., Meade TJ; Departments of Chemistry, Molecular Biosciences, Neurobiology, and Radiology, Northwestern University, Evanston, IL, 60208-3113, USA. |
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| Jazyk: | angličtina |
| Zdroj: | ChemMedChem [ChemMedChem] 2022 Apr 20; Vol. 17 (8), pp. e202200025. Date of Electronic Publication: 2022 Mar 18. |
| DOI: | 10.1002/cmdc.202200025 |
| Abstrakt: | The aberrant activation of the Gli family of zinc finger transcription factors (ZFTFs) is associated with several types of human cancer, including medulloblastoma and basal cell carcinoma. We have reported the use of cobalt(III) Schiff-base complexes (Co(III)-sb) as potent inhibitors of ZFTFs in vivo. These complexes inhibit transcription by displacing the zinc finger domain's structural Zn(II) ion, destabilizing the alpha helix necessary for DNA recognition. Here, we describe the use of Co(III)-sb complexes for the selective inhibition of Gli1. Spectroscopic and computational studies of the Gli1 DNA binding domain found that Co(III)-sb displaced Zn(II) through direct coordination with the His residues of the Cys (© 2022 Wiley-VCH GmbH.) |
| Databáze: | MEDLINE |
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