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Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a
We recently presented Stafia‐1 as the first chemical entity that inhibits the transcription factor STAT5a with selectivity over the highly homologous STAT5b. Stafia‐1, which was identified from a series of symmetrically substituted m‐terphenyl phosphates, binds to the interface between the SH2 domai...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303812/ https://www.ncbi.nlm.nih.gov/pubmed/34905258 http://dx.doi.org/10.1002/cbic.202100603 |
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author | Müller‐Klieser, Daniel Berg, Thorsten |
author_facet | Müller‐Klieser, Daniel Berg, Thorsten |
author_sort | Müller‐Klieser, Daniel |
collection | PubMed |
description | We recently presented Stafia‐1 as the first chemical entity that inhibits the transcription factor STAT5a with selectivity over the highly homologous STAT5b. Stafia‐1, which was identified from a series of symmetrically substituted m‐terphenyl phosphates, binds to the interface between the SH2 domain and the linker domain of STAT5a. Here, we outline a synthetic strategy for the synthesis of asymmetrically substituted m‐terphenyl phosphates, which can be tailored to address their asymmetric STAT5a binding site in a more specific manner. The asymmetrically substituted m‐terphenyl phosphate with the highest activity against STAT5a was converted to a phosphatase‐stable monofluoromethylene phosphonate. The synthetic methodology and activity analysis described here provide first insights into the structure‐activity relationships of m‐terphenyl phosphates for use as selective STAT5a inhibitors. |
format | Online Article Text |
id | pubmed-9303812 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-93038122022-07-28 Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a Müller‐Klieser, Daniel Berg, Thorsten Chembiochem Research Articles We recently presented Stafia‐1 as the first chemical entity that inhibits the transcription factor STAT5a with selectivity over the highly homologous STAT5b. Stafia‐1, which was identified from a series of symmetrically substituted m‐terphenyl phosphates, binds to the interface between the SH2 domain and the linker domain of STAT5a. Here, we outline a synthetic strategy for the synthesis of asymmetrically substituted m‐terphenyl phosphates, which can be tailored to address their asymmetric STAT5a binding site in a more specific manner. The asymmetrically substituted m‐terphenyl phosphate with the highest activity against STAT5a was converted to a phosphatase‐stable monofluoromethylene phosphonate. The synthetic methodology and activity analysis described here provide first insights into the structure‐activity relationships of m‐terphenyl phosphates for use as selective STAT5a inhibitors. John Wiley and Sons Inc. 2021-12-29 2022-02-16 /pmc/articles/PMC9303812/ /pubmed/34905258 http://dx.doi.org/10.1002/cbic.202100603 Text en © 2021 The Authors. ChemBioChem published by Wiley-VCH GmbH https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Articles Müller‐Klieser, Daniel Berg, Thorsten Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a |
title | Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a |
title_full | Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a |
title_fullStr | Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a |
title_full_unstemmed | Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a |
title_short | Asymmetrically Substituted m‐Terphenyl Phosphates Inhibit the Transcription Factor STAT5a |
title_sort | asymmetrically substituted m‐terphenyl phosphates inhibit the transcription factor stat5a |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9303812/ https://www.ncbi.nlm.nih.gov/pubmed/34905258 http://dx.doi.org/10.1002/cbic.202100603 |
work_keys_str_mv | AT mullerklieserdaniel asymmetricallysubstitutedmterphenylphosphatesinhibitthetranscriptionfactorstat5a AT bergthorsten asymmetricallysubstitutedmterphenylphosphatesinhibitthetranscriptionfactorstat5a |