Academic Journal
Functional Disruption of Gli1‐DNA Recognition via a Cobalt(III) Complex
| العنوان: | Functional Disruption of Gli1‐DNA Recognition via a Cobalt(III) Complex |
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| المؤلفون: | Brue, Christopher R., Dukes, Meghan W., Masotti, Meghan, Holmgren, Robert, Meade, Thomas J. |
| المساهمون: | National Institutes of Health, Northwestern University |
| المصدر: | ChemMedChem ; volume 17, issue 8 ; ISSN 1860-7179 1860-7187 |
| بيانات النشر: | Wiley |
| سنة النشر: | 2022 |
| المجموعة: | Wiley Online Library (Open Access Articles via Crossref) |
| الوصف: | 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 2 His 2 Zn(II) binding site. As a result, there is a dose‐dependent degradation of the alpha‐helix content in the DNA binding domain of Gli1 and corresponding inhibition of consensus sequence recognition. We conclude that this strategy is well suited for the development of new and potent inhibitors of Gli1. |
| نوع الوثيقة: | article in journal/newspaper |
| اللغة: | English |
| DOI: | 10.1002/cmdc.202200025 |
| الاتاحة: | http://dx.doi.org/10.1002/cmdc.202200025 https://onlinelibrary.wiley.com/doi/pdf/10.1002/cmdc.202200025 https://onlinelibrary.wiley.com/doi/full-xml/10.1002/cmdc.202200025 |
| Rights: | http://onlinelibrary.wiley.com/termsAndConditions#vor |
| رقم الانضمام: | edsbas.C53B2E8 |
| قاعدة البيانات: | BASE |
| DOI: | 10.1002/cmdc.202200025 |
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