Aziridine-Mediated Ligation and Site-Specific Modification of Unprotected Peptides

• DOI: 10.1021/ja207133t
• Publication Date: 2011-11-23T19:10:03Z
• Authors: Frank Brock Dyer; Chung-Min Park; Ryan Joseph; Philip Garner
• Keywords: Aziridine; Reactivity; Chemical Ligation

A synthesis of aziridine-containing peptides via the Cu(II)-promoted coupling unprotected peptide thioacids and N-H aziridine-2-carbonyl is reported. The unique reactivity resulting N-acylated facilitates their subsequent regioselective stereoselective nucleophilic ring-opening to give that are specifically modified at ligation site. aziridine-mediated concept exemplified using H(2)O as nucleophile, producing a Xaa-Thr linkage (where Xaa can be an epimerizable hindered amino acid). overall process compatible with variety acid functionality, most notably N-terminal Lys side chain amines.