Bioorthogonal Deprotection on the Dendritic Cell Surface for Chemical Control of Antigen Cross‐Presentation

Abstract

The activation of CD8(+) T-cells requires the uptake of exogenous polypeptide antigens and proteolytic processing of these antigens to octamer or nonamer peptides, which are loaded on MHC-I complexes and presented to the T-cell. By using an azide as a bioorthogonal protecting group rather than as a ligation handle, masked antigens were generated-antigens that are not recognized by their cognate T-cell unless they are deprotected on the cell using a Staudinger reduction.

Inverse electron demand Diels–Alder reactions in chemical biology

“…This azide-to-amine conversion was employed for the activation of a doxorubicin prodrug, 339 DNA-templated release of fluorophores and functional molecules, 340 as well as controlled activation of epitopes on the surface. 341 Apart from this bioorthogonal reductive transition, azide could also be decaged to give amines by reaction with TCO (Fig. 49d).…”

Detection of bioorthogonal groups by correlative light and electron microscopy allows imaging of degraded bacteria in phagocytes

“…Bioorthogonal non-canonical amino acid tagging (BONCAT) 14,15 for pan-proteomic incorporation of bioorthogonal groups 16,17 would allow the labelling of a wide range of bacterial species without the need for genetic modification. 18 Furthermore, unlike reporter proteins, bioorthogonal groups, such as azides 19,20 have been shown to be stable in the harsh chemical environments of the phagolysosomal system and should therefore be detectable when extensive proteolysis has occurred.…”

Harnessing Endogenous Formate for Antibacterial Prodrug Activation by in cellulo Ruthenium‐Mediated Transfer Hydrogenation Reaction

“…As a biorthogonal functional group, the azide moiety has enabled an array of exciting biological applications such as bioconjugation, labelling, prodrug activation, protein function control, and cell activation . However, studies into its efficacy as a caging tool have been limited to Staudinger reduction, trans ‐cyclooctene reduction, and photo/catalytic reduction by [Fe(TPP)]Cl and [Ru(bpy) 2 (5‐NCS‐phen)](PF 6 ) 2 (Supporting Information, Figure S1) . Finding new efficacious organometallic catalysts that can reliably activate azide caging group within a complex intracellular environment utilizing native reagents remains a challenge.…”