Peptide α-thioesters are fundamental building blocks in protein science with increasing importance in peptide drug development. The employment of peptide α-thioesters in native chemical ligation reactions gives access to small bioactive proteins, complex venom peptides and cyclic peptides as well as labeled, complex peptidic molecules. Whereas the native chemical ligation technology is well established, the synthesis of the broadly employed key, peptide α-thioester building blocks remains a bottleneck in this powerful technology.
Consequently, an efficient high throughput synthetic strategy to access peptide a-thioester building blocks is essential.
Here we present a novel synthetic route, which employs a safety catch linker and parallel Boc-chemistry to generate libraries of peptide α-thioesters.
These essential reactive intermediates were cyclized via native chemical ligation to give access to a library of cyclic peptides.
We exemplify how the developed high throughput synthetic libraries can have the potential for peptide turn mimetic discovery.