High Throughput Synthesis of Peptide α-Thioesters Through the Use of 'Volatilizable' Support

摘要

Native chemical ligation has facilitated the total synthesis of small- and medium-sized proteins and cyclic peptides and has thus opened the world of proteins to the tools of organic chemistry. Native chemical ligation relies on the combination of two steps. In the first step, a C-terminal peptide α-thioester is reacted with an N-terminal cysteine peptide. The second step involves a rapid intramolecular S- to N-shift forming an amide bond at the ligation site. Recently, the scope of ligation methods has expanded from N-terminal cysteine to noncysteine residues by employing auxiliary thiols, thus increasing the applicability of the approach. C-terminal peptide α-thioesters are key intermediates in all of these methodologies. This need for C-terminal peptide α-thioesters has stimulated the development in our laboratory of simple and efficient synthetic methods for this class of peptides.