N-acyl-7-nitroindolines are photoreactive compounds that are known to acylate a number of different nucleophiles in inert aprotic solvents under neutral conditions when illuminated with near ultraviolet light. While a nitroindoline-based linker has been developed for solid phase peptide synthesis (SPPS) producing C-terminal peptide thioesters and hydrazides, the photochemical C-terminal derivatization has not been expanded to glycopeptides. To further explore this photochemistry on peptide and glycopeptide model compounds, we have assembled a MUC1-derived peptide and Tn or STn-containing MUC1 glycopeptides with a C-terminal photoreactive 7-nitroindoline linker attached to Sieber amide resin by solid phase peptide synthesis using the Fmoc strategy. The resulting extended linker is dual functional and allows for the cleavage of fully protected photoreactive peptides/glycopeptides from the resin with dilute trifluoroacetic acid, which can be further derivatized to C-terminal acids, amides and thioesters in solution. Alternatively, the direct photorelease of protected peptide/glycopeptide acids, as well as amides from the resin is also possible. Here we demonstrate that N-peptidyl and N-glycopeptidyl 7-nitrindolines can be photochemically converted into their peptide acids, activated esters, amides, or aromatic thioesters when illuminated with near ultraviolet light in the presence of an appropriate nucleophile (water, hydroxybenzotriazole, a primary amine, or N-hydroxysuccinimde followed by treatment with benzenethiol) thus demonstrating the chemical versatility of N-peptidyl-7-nitroindolines and N-glycopeptidyl-7-nitroindolines.

Versatility of N-peptidyl nitroindolines for the formation of peptide/glycopeptide acids, amides, and thioesters

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.