Total Chemical Synthesis of a 304 Amino Acid K48-Linked Tetraubiquitin Protein

A new record: The largest chemically synthesized polypeptide composed of 304 residues, which corresponds to folded K48‐tetraubiquitin, has been achieved (see scheme). The presented synthetic method could be applied to any of the remaining tetraubiquitin chains, and should ultimately assist ongoing efforts to unravel how the remarkable diversity of ubiquitin signaling is achieved.