A lysosome-targeted tetrazine for organelle-specific click-to-release chemistry in antigen presenting cells

Ligthart, N.A.M.; Geus, M.A.R. de; Plassche, M.A.T. van de; Torres Garcia, D.; Isendoorn, M.M.E.; Reinalda, L.; ... ; Kasteren, S.I. van (2023)

Article / Letter to editor

Bioorthogonal deprotectionsare readily used to control biologicalfunction in a cell-specific manner. To further improve the spatialresolution of these reactions, we here present a lysosome-targetedtetrazine for an organelle-specific deprotection reaction. We showthat trans-cyclooctene deprotection with this reagentcan be used to control the biological activity of ligands for invariantnatural killer T cells in the lysosome to shed light on the processingpathway in antigen presenting cells. We then use the lysosome-targetedtetrazine to show that long peptide antigens used for CD8(+) T cell activation do not pass through this organelle, suggestinga role for the earlier endosomal compartments for their processing.

• All authors: Ligthart, N.A.M.; Geus, M.A.R. de; Plassche, M.A.T. van de; Torres Garcia, D.; Isendoorn, M.M.E.; Reinalda, L.; Ofman, D.E.; Leeuwen, T. van; Kasteren, S.I. van
• Date: 2023-06-03
• Journal: Journal of the American Chemical Society
• Volume: 145
• Issue: 23
• Pages: 12630 - 12640
• DOI: doi:10.1021/jacs.3c02139
• Link: https://pubs.acs.org/doi/10.1021/jacs.3c02139