Chemical Bypass of Intein-Catalyzed N–S Acyl Shift in Protein Splicing


  • We thank Alexandra Wasmuth and Julian Matern for discussions. Financial support from the Deutsche Forschungsgemeinschaft (grant MO 1073/3-1,2) is acknowledged.


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Spliced: An N-methyl group was introduced at the scissile peptide bond in a semisynthetic intein precursor. With the chemical modification, thioester formation and protein splicing was observed in the absence of the otherwise critical block B histidine. This finding shows the role of the histidine in ground-state destabilization and rules out other previously proposed roles for this residue in the protein splicing pathway.