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Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization

[Image: see text] Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited ut...

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Autores principales: Czlapinski, Jennifer L., Schelle, Michael W., Miller, Lawrence W., Laughlin, Scott T., Kohler, Jennifer J., Cornish, Virginia W., Bertozzi, Carolyn R.
Formato: Texto
Lenguaje:English
Publicado: American Chemical Society 2008
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709988/
https://www.ncbi.nlm.nih.gov/pubmed/18788807
http://dx.doi.org/10.1021/ja8037728
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author Czlapinski, Jennifer L.
Schelle, Michael W.
Miller, Lawrence W.
Laughlin, Scott T.
Kohler, Jennifer J.
Cornish, Virginia W.
Bertozzi, Carolyn R.
author_facet Czlapinski, Jennifer L.
Schelle, Michael W.
Miller, Lawrence W.
Laughlin, Scott T.
Kohler, Jennifer J.
Cornish, Virginia W.
Bertozzi, Carolyn R.
author_sort Czlapinski, Jennifer L.
collection PubMed
description [Image: see text] Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. Here we report a new biocompatible CID, Tmp-SLF, which dimerizes E. coli DHFR and FKBP and has no endogenous mammalian targets that would lead to unwanted in vivo side effects. We employed Tmp-SLF to modulate gene expression in a yeast three-hybrid assay. Finally, we engineered the Golgi-resident glycosyltransferase FucT7 for tunable control by Tmp-SLF in mammalian cells.
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spelling pubmed-27099882009-07-14 Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization Czlapinski, Jennifer L. Schelle, Michael W. Miller, Lawrence W. Laughlin, Scott T. Kohler, Jennifer J. Cornish, Virginia W. Bertozzi, Carolyn R. J Am Chem Soc [Image: see text] Chemical inducers of dimerization (CIDs) are cell-permeable small molecules capable of dimerizing two protein targets. The most widely used CID, the natural product rapamycin and its relatives, is immunosuppressive due to interactions with endogenous targets and thus has limited utility in vivo. Here we report a new biocompatible CID, Tmp-SLF, which dimerizes E. coli DHFR and FKBP and has no endogenous mammalian targets that would lead to unwanted in vivo side effects. We employed Tmp-SLF to modulate gene expression in a yeast three-hybrid assay. Finally, we engineered the Golgi-resident glycosyltransferase FucT7 for tunable control by Tmp-SLF in mammalian cells. American Chemical Society 2008-09-13 2008-10-08 /pmc/articles/PMC2709988/ /pubmed/18788807 http://dx.doi.org/10.1021/ja8037728 Text en Copyright © 2008 American Chemical Society http://pubs.acs.org This is an open-access article distributed under the ACS AuthorChoice Terms & Conditions. Any use of this article, must conform to the terms of that license which are available at http://pubs.acs.org. 40.75
spellingShingle Czlapinski, Jennifer L.
Schelle, Michael W.
Miller, Lawrence W.
Laughlin, Scott T.
Kohler, Jennifer J.
Cornish, Virginia W.
Bertozzi, Carolyn R.
Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization
title Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization
title_full Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization
title_fullStr Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization
title_full_unstemmed Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization
title_short Conditional Glycosylation in Eukaryotic Cells Using a Biocompatible Chemical Inducer of Dimerization
title_sort conditional glycosylation in eukaryotic cells using a biocompatible chemical inducer of dimerization
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2709988/
https://www.ncbi.nlm.nih.gov/pubmed/18788807
http://dx.doi.org/10.1021/ja8037728
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