Serine/Threonine Ligation and Cysteine/Penicillamine Ligation.

Serine/threonine ligation (STL) and cysteine/penicillamine ligation (CPL) are highly chemo- and regioselective reactions between unprotected peptides with C-terminus salicylaldehyde esters and unprotected peptides with N-terminus serine/threonine or cysteine/penicillamine, which serve as powerful tools for cyclic peptide natural product and chemical protein synthesis. Herein, we introduce the preparation of C-terminal peptide salicylaldehyde esters, serine/threonine ligation, cysteine/penicillamine ligation, and subsequent acidolysis.