Reversible and Noncompetitive Inhibition of β-Tryptase by Protein Surface Binding of Tetravalent Peptide Ligands Identified from a Combinatorial Split-Mix Library

Molecular plug: On‐bead screening of a combinatorial library of 216 tetravalent oligopeptides reveals highly specific, noncompetitive inhibitors of the serine protease β‐tryptase with nanomolar affinity. The ligands most likely bind to the protein surface and act as a molecular plug that blocks access to the active sites, which are buried inside a central cavity (see picture).