Enabling Cysteine-Free Native Chemical Ligation at Challenging Junctions with a Ligation Auxiliary Capable of Base Catalysis.

Ligation auxiliaries are used in chemical protein synthesis to extend the scope of native chemical ligation (NCL) beyond cysteine. However, auxiliary-mediated ligations at sterically demanding junctions have been difficult. Often the thioester intermediate formed in the thiol exchange step of NCL accumulates because the subsequent S→N acyl transfer is extremely slow.