Proximity-enabled bioreactivity to generate covalent peptide inhibitors of p53–Mdm4

Although small molecule covalent inhibitors have been widely explored, macromolecular covalent inhibitors are more difficult to design and implement. Here we present a strategy to enable a peptide to bind to its target protein covalently via proximity-enabled bioreactivity, improving its activity of inhibiting the p53–Mdm4 interaction by 10-fold.