Peptide Logic Circuits Based on Chemoenzymatic Ligation for Programmable Cell Apoptosis

A novel and versatile peptide‐based bio‐logic system capable of regulating cell function is developed using sortase A (SrtA), a peptide ligation enzyme, as a generic processor. By modular peptide design, we demonstrate that mammalian cells apoptosis can be programmed by peptide‐based logic operations, including binary and combination gates (AND, INHIBIT, OR, and AND‐INHIBIT), and a complex sequential logic circuit (multi‐input keypad lock). Moreover, a proof‐of‐concept peptide regulatory circuit was developed to analyze the expression profile of cell‐secreted protein biomarkers and trigger cancer‐cell‐specific apoptosis. It's only bio‐logical: A versatile peptide‐based bio‐logic system has been developed by using sortase A (SrtA), an emerging peptide ligation enzyme, as a generic processor. By modular design of peptide inputs, cancer cells apoptosis can be programmed by peptide logic circuits.