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

Abstract

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.