title: Native chemical ligation at a base-labile 4-mercaptobutyrate N(α)-auxiliary.
abstract: Native chemical ligation (NCL) proceeds via a S-N acyl shift and, therefore, requires N-terminal cysteine. N(α)-auxiliaries have long been used to enable NCL beyond cysteine. However, the reversibility of the S-N acyl shift under the acidic conditions used to remove the commonly applied N-benzyl auxiliaries limits the scope of this reaction. Herein, we introduce a new class of N(α)-auxiliary which is designed for removal under mild basic conditions. The 3-N-linked 4-mercaptobutyrate auxiliary is readily synthesized in a single step and enables introduction on solid phase by means of reductive amination. The usefulness of the new auxiliary was demonstrated in the synthesis of the anti-microbial C-terminal domain of Dermicidine-1L.
authors.affiliation: Institut für Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
authors.forename: Ziv
authors.initials: Z
authors.lastname: Harpaz
authors.affiliation: Institut für Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Loibl
authors.affiliation: Institut für Chemie, Humboldt Universität zu Berlin, Brook-Taylor-Straße 2, 12489 Berlin, Germany.
authors.forename: Oliver
authors.initials: O
authors.lastname: Seitz
mesh_terms: D002087:Butyrates / Q000138:chemical synthesis / Q000737:chemistry*; D015394:Molecular Structure; D017434:Protein Structure, Tertiary
chemical_list: D002087:Butyrates; C067656:4-mercaptobutyrate
keywords: Auxiliary assisted NCL; Dermicidine; Extending NCL; Native chemical ligation; Peptide coupling; Radicals; Total chemical protein synthesis