Chemical Synthesis of Proteins Using an o -Nitrobenzyl Group as a Robust Temporary Protective Group for N-Terminal Cysteine Protection.

We report here a robust and practical strategy for chemical protein synthesis using an o -nitrobenzyl group as a temporary protective group for an N-terminal cysteine residue of intermediate hydrazide fragments. By reinvestigating the photoremoval of an o -nitrobenzyl group, we establish a robust and reliable strategy for its quantitative photodeprotection. The o -nitrobenzyl group is completely stable to oxidative NaNO 2 treatment and has been applied to the convergent chemical synthesis of programmed death ligand 1 fragment, providing a practical avenue for hydrazide-based native chemical ligation.