Discovery of a Plant 14‐3‐3 Inhibitor Possessing Isoform Selectivity and In Planta Activity

Abstract

Synthetic modulators for plant 14‐3‐3s are promising chemical tools both for understanding the 14‐3‐3‐related signaling pathways and controlling plant physiology. Here, we describe a novel small‐molecule inhibitor for 14‐3‐3 proteins ofArabidopsis thaliana. The inhibitor was identified from unexpected products in DMSO stock solution of an in‐house chemical library. Mass spectroscopy, mutant‐based analyses, fluorescence polarization assays, and thermal shift assaysrevealed that the inhibitor covalently binds to an allosteric site of 14‐3‐3 with isoform selectivity. Moreover, infiltration of the inhibitor to Arabidopsis leaves suppressed the stomatal aperture. The inhibitor should provide a new insight into the design of potent and isoform‐selective 14‐3‐3 modulators.