Auxiliaries in Native Chemical Ligation: Exploring the Reactivity Landscape with new Scaffolds

The auxiliary-mediated native chemical ligation (NCL) serves as an essential tool in expanding the scope of NCL beyond cysteine, allowing for the selection of any amide bond for retrosynthetic scission of proteins.While long conceived as limited to "easy junctions" like Gly-Gly, our newest generation of auxiliaries are capable of tackling reactions of two -branched amino acids and are feasible for ligation with phosphorylated or glycosylated amino acids at pH 7 or in acidic medium. Auxiliaries in Native Chemical Ligation: Exploring the Reactivity Landscape with new Scaffolds auxiliary-mediated NCL can be enhanced via intramolecular base catalysis [1, 2, 3] A new cleavage paradigm Acid-base catalysis benzyl-type MPE MPyEGly-Gly