Using chemistry to investigate the molecular consequences of protein ubiquitylation

Chemistry has long played an indispensable role in biological discovery through the synthesis of homogeneous, structurally defined material. With continuing advances in the area of synthetic protein chemistry, chemists are able to prepare increasingly large and complex proteins that have enabled key biochemical experiments. Here, we describe some of the chemical methods that have been applied to the synthesis of ubiquitylated proteins, as ubiquitylation is a crucial post-translational modification that mediates a variety of important biological effects on substrate proteins.