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.