A Lysosome-Targeted Tetrazine for Organelle-Specific Click-to-Release Chemistry in Antigen Presenting Cells
Bioorthogonal deprotections are readily used to control biological function in a cell-specific manner. To further improve the spatial resolution of these reactions, we here present a lysosome-targeted tetrazine for an organelle-specific deprotection reaction. We show that trans-cyclooctene deprotect...
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Veröffentlicht in: | Journal of the American Chemical Society 2023-06, Vol.145 (23), p.12630-12640 |
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creator | Ligthart, Nina A.M. de Geus, Mark A.R. van de Plassche, Merel A.T. Torres García, Diana Isendoorn, Marjolein M.E. Reinalda, Luuk Ofman, Daniëlle van Leeuwen, Tyrza van Kasteren, Sander I. |
description | Bioorthogonal deprotections are readily used to control biological function in a cell-specific manner. To further improve the spatial resolution of these reactions, we here present a lysosome-targeted tetrazine for an organelle-specific deprotection reaction. We show that trans-cyclooctene deprotection with this reagent can be used to control the biological activity of ligands for invariant natural killer T cells in the lysosome to shed light on the processing pathway in antigen presenting cells. We then use the lysosome-targeted tetrazine to show that long peptide antigens used for CD8+ T cell activation do not pass through this organelle, suggesting a role for the earlier endosomal compartments for their processing. |
doi_str_mv | 10.1021/jacs.3c02139 |
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To further improve the spatial resolution of these reactions, we here present a lysosome-targeted tetrazine for an organelle-specific deprotection reaction. We show that trans-cyclooctene deprotection with this reagent can be used to control the biological activity of ligands for invariant natural killer T cells in the lysosome to shed light on the processing pathway in antigen presenting cells. We then use the lysosome-targeted tetrazine to show that long peptide antigens used for CD8+ T cell activation do not pass through this organelle, suggesting a role for the earlier endosomal compartments for their processing.</description><identifier>ISSN: 0002-7863</identifier><identifier>EISSN: 1520-5126</identifier><identifier>DOI: 10.1021/jacs.3c02139</identifier><identifier>PMID: 37269296</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Antigen-Presenting Cells ; Click Chemistry ; Heterocyclic Compounds ; Lysosomes ; Organelles ; Peptides</subject><ispartof>Journal of the American Chemical Society, 2023-06, Vol.145 (23), p.12630-12640</ispartof><rights>2023 The Authors. Published by American Chemical Society</rights><rights>2023 The Authors. 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Am. Chem. Soc</addtitle><description>Bioorthogonal deprotections are readily used to control biological function in a cell-specific manner. To further improve the spatial resolution of these reactions, we here present a lysosome-targeted tetrazine for an organelle-specific deprotection reaction. We show that trans-cyclooctene deprotection with this reagent can be used to control the biological activity of ligands for invariant natural killer T cells in the lysosome to shed light on the processing pathway in antigen presenting cells. 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Am. Chem. Soc</addtitle><date>2023-06-14</date><risdate>2023</risdate><volume>145</volume><issue>23</issue><spage>12630</spage><epage>12640</epage><pages>12630-12640</pages><issn>0002-7863</issn><eissn>1520-5126</eissn><abstract>Bioorthogonal deprotections are readily used to control biological function in a cell-specific manner. To further improve the spatial resolution of these reactions, we here present a lysosome-targeted tetrazine for an organelle-specific deprotection reaction. We show that trans-cyclooctene deprotection with this reagent can be used to control the biological activity of ligands for invariant natural killer T cells in the lysosome to shed light on the processing pathway in antigen presenting cells. 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subjects | Antigen-Presenting Cells Click Chemistry Heterocyclic Compounds Lysosomes Organelles Peptides |
title | A Lysosome-Targeted Tetrazine for Organelle-Specific Click-to-Release Chemistry in Antigen Presenting Cells |
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