A Lysosome-Targeted Tetrazine for Organelle-Specific Click-to-Release Chemistry in Antigen Presenting Cells.

Autor: Ligthart NAM; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., de Geus MAR; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., van de Plassche MAT; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., Torres García D; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., Isendoorn MME; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., Reinalda L; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., Ofman D; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., van Leeuwen T; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands., van Kasteren SI; Leiden Institute of Chemistry and The Institute for Chemical Immunology, Leiden University, Einsteinweg 55, 2333 CC Leiden, The Netherlands.
Jazyk: angličtina
Zdroj: Journal of the American Chemical Society [J Am Chem Soc] 2023 Jun 14; Vol. 145 (23), pp. 12630-12640. Date of Electronic Publication: 2023 Jun 03.
DOI: 10.1021/jacs.3c02139
Abstrakt: 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.
Databáze: MEDLINE