Intrinsic Allosteric Inhibition of Signaling Proteins by Targeting Rare Interaction States Detected by High‐Pressure NMR Spectroscopy

Abstract

A new type of allosteric inhibition by small molecules is proposed that should be applicable to all proteins involved intrinsically in protein–protein interactions. It is based on targeting their rare interaction states that can be detected by high-pressure NMR spectroscopy (see picture). An example is the Ras-protein where the protein–protein interaction of Ras with effectors can be modulated by small compounds that bind to the conformational states 1(T) or 1(0).