Mechanisms of reversible protein deactivation are foundational in life. For example, these mechanisms are used by cells in signaling cascades, whereby multiple enzymes undergo controlled activity switch on/off events, which ultimately connects external signals to internal cellular responses. The Zelikin group focused on the protein cysteinome – proteins with cysteine amino acid – and designed chemical zymogens such that enzyme activity can be switched on demand using tools of chemistry. The key to the proposed designs in the reversible character of disulfide linkages.

Three classes of zymogens were designed and applied to three different enzymes, thus presenting a robust, reliable chemical platform for zymogen design. These are now being developed further, towards establishing signaling in artificial cells.