Tag and release: strategies for the intracellular cleavage of protein conjugates

Attaching a functional moiety to a protein is required for a wealth of applications, comprising targeted delivery, controlling of enzyme activity, and prodrug-based therapy. Targeting intracellular processes requires the cellular delivery of the protein. While at first, a stable connection between the protein and the modification is desired, once inside the cell, the conjugate might be cleaved again to restore or activate the function of the individual parts. This can be achieved by employing cleavable linkages in conjugates, which are responsive to chemical or enzymatic stimuli inside cells. In this overview we describe strategies, how such entities can be introduced into proteins and how selective intracellular cleavage can be accomplished.