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

作者：Dyer Frank Brock; Park Chung Min; Joseph Ryan; Garner Philip^*

来源：Journal of the American Chemical Society, 2011, 133(50): 20033-20035.

DOI：10.1021/ja207133t

A synthesis of aziridine-containing peptides via the Cu(II)-promoted coupling of unprotected peptide thioacids and N-H aziridine-2-carbonyl peptides is reported. The unique reactivity of the resulting N-acylated aziridine-2-carbonyl peptides facilitates their subsequent regioselective and stereoselective nucleophilic ring-opening to give unprotected peptides that are specifically modified at the ligation site. The aziridine-mediated peptide ligation concept is exemplified using H2O as the nucleophile, producing a Xaa-Thr linkage (where Xaa can be an epimerizable and hindered amino acid). The overall process is compatible with a variety of unprotected amino acid functionality, most notably the N-terminal and Lys side chain amines.

• 出版日期2011-12-21