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Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway
CCG-1423 and related analogues represent a new class of inhibitors of Rho/MKL1/SRF-mediated gene transcription, a pathway that has been implicated in both cancer and fibrosis. The molecular target for these compounds is unknown. To facilitate its identification, a series of tag-free photoaffinity pr...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Beilstein-Institut
2013
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678708/ https://www.ncbi.nlm.nih.gov/pubmed/23766813 http://dx.doi.org/10.3762/bjoc.9.111 |
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author | Bell, Jessica L Haak, Andrew J Wade, Susan M Sun, Yihan Neubig, Richard R Larsen, Scott D |
author_facet | Bell, Jessica L Haak, Andrew J Wade, Susan M Sun, Yihan Neubig, Richard R Larsen, Scott D |
author_sort | Bell, Jessica L |
collection | PubMed |
description | CCG-1423 and related analogues represent a new class of inhibitors of Rho/MKL1/SRF-mediated gene transcription, a pathway that has been implicated in both cancer and fibrosis. The molecular target for these compounds is unknown. To facilitate its identification, a series of tag-free photoaffinity probes was designed and synthesized, each one containing a photoactivatable group and an acetylenic end group for subsequent attachment to a fluorescent tag using click chemistry. All were confirmed to maintain biological activity in a cell-based assay for inhibition of SRE-Luc expression. The functional activity of the most potent probe 24 was further confirmed in an assay for PC-3 cell migration. Photolysis of 24 in intact PC-3 cells followed by cell lysis, click ligation of a fluorescent dye, and gel electrophoresis revealed specific labeling of a single 24 kDa band that could be blocked with an active competitor. Future work will focus on identifying the labeled protein(s). |
format | Online Article Text |
id | pubmed-3678708 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
publisher | Beilstein-Institut |
record_format | MEDLINE/PubMed |
spelling | pubmed-36787082013-06-13 Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway Bell, Jessica L Haak, Andrew J Wade, Susan M Sun, Yihan Neubig, Richard R Larsen, Scott D Beilstein J Org Chem Letter CCG-1423 and related analogues represent a new class of inhibitors of Rho/MKL1/SRF-mediated gene transcription, a pathway that has been implicated in both cancer and fibrosis. The molecular target for these compounds is unknown. To facilitate its identification, a series of tag-free photoaffinity probes was designed and synthesized, each one containing a photoactivatable group and an acetylenic end group for subsequent attachment to a fluorescent tag using click chemistry. All were confirmed to maintain biological activity in a cell-based assay for inhibition of SRE-Luc expression. The functional activity of the most potent probe 24 was further confirmed in an assay for PC-3 cell migration. Photolysis of 24 in intact PC-3 cells followed by cell lysis, click ligation of a fluorescent dye, and gel electrophoresis revealed specific labeling of a single 24 kDa band that could be blocked with an active competitor. Future work will focus on identifying the labeled protein(s). Beilstein-Institut 2013-05-21 /pmc/articles/PMC3678708/ /pubmed/23766813 http://dx.doi.org/10.3762/bjoc.9.111 Text en Copyright © 2013, Bell et al. https://creativecommons.org/licenses/by/2.0https://www.beilstein-journals.org/bjoc/termsThis is an Open Access article under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The license is subject to the Beilstein Journal of Organic Chemistry terms and conditions: (https://www.beilstein-journals.org/bjoc/terms) |
spellingShingle | Letter Bell, Jessica L Haak, Andrew J Wade, Susan M Sun, Yihan Neubig, Richard R Larsen, Scott D Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway |
title | Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway |
title_full | Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway |
title_fullStr | Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway |
title_full_unstemmed | Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway |
title_short | Design and synthesis of tag-free photoprobes for the identification of the molecular target for CCG-1423, a novel inhibitor of the Rho/MKL1/SRF signaling pathway |
title_sort | design and synthesis of tag-free photoprobes for the identification of the molecular target for ccg-1423, a novel inhibitor of the rho/mkl1/srf signaling pathway |
topic | Letter |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3678708/ https://www.ncbi.nlm.nih.gov/pubmed/23766813 http://dx.doi.org/10.3762/bjoc.9.111 |
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