Enzyme‐Cleavable Linkers for Protein Chemical Synthesis through Solid‐Phase Ligations

The total synthesis of long proteins requires the assembly multiple fragments through successive ligations. need for intermediate purification steps is a strong limitation, particularly in terms overall yield. One solution to this problem would be solid-supported chemical ligation (SPCL), which first peptide segment must immobilized on SPCL-compatible solid support linker that can cleaved under very mild conditions release assembled protein. cleavage SPCL linkers has previously required sometimes incompatible with sensitive protein targets. Herein, we describe an alternative enzymatic approach trigger extremely and selective conditions. Optimization structure use small enzyme able diffuse into were key success strategy. We demonstrated its utility by three segments basis native afford 15 kDa polypeptide.