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A Lysosome-Targeted Tetrazine for Organelle-Specific Click-to-Release Chemistry in Antigen Presenting Cells
Journal of the American Chemical Society ( IF 15.0 ) Pub Date : 2023-06-03 , DOI: 10.1021/jacs.3c02139
Nina A M Ligthart 1 , Mark A R de Geus 1 , Merel A T van de Plassche 1 , Diana Torres García 1 , Marjolein M E Isendoorn 1 , Luuk Reinalda 1 , Daniëlle Ofman 1 , Tyrza van Leeuwen 1 , Sander I van Kasteren 1
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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.

中文翻译:

用于抗原呈递细胞中细胞器特异性点击释放化学的溶酶体靶向四嗪

生物正交脱保护很容易用于以细胞特异性方式控制生物功能。为了进一步提高这些反应的空间分辨率,我们在这里提出了一种用于细胞器特异性脱保护反应的溶酶体靶向四嗪。我们表明,使用该试剂进行的反式环辛烯脱保护可用于控制溶酶体中不变自然杀伤 T 细胞配体的生物活性,从而阐明抗原呈递细胞中的加工途径。然后,我们使用靶向溶酶体的四嗪来显示用于 CD8 + T 细胞激活的长肽抗原不会通过该细胞器,表明早期内体区室在其加工过程中的作用。
更新日期:2023-06-03
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