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
Hauptverfasser: 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.
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container_end_page 12640
container_issue 23
container_start_page 12630
container_title Journal of the American Chemical Society
container_volume 145
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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source ACS Publications; MEDLINE
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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