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

Authors :: Nishiyama K
Aihara Y
Suzuki T
Takahashi K
Kinoshita T
Dohmae N
Sato A
Hagihara S
Source :: Angewandte Chemie (International ed. in English) [Angew Chem Int Ed Engl] 2024 Jul 01; Vol. 63 (27), pp. e202400218. Date of Electronic Publication: 2024 May 27.
Publication Year :: 2024
Abstract: Synthetic modulators of plant 14-3-3s are promising chemical tools both for understanding the 14-3-3-related signaling pathways and controlling plant physiology. Herein, we describe a novel small-molecule inhibitor for 14-3-3 proteins of Arabidopsis thaliana. The inhibitor was identified from unexpected products in a stock solution in dimethyl sulfoxide (DMSO) of an in-house chemical library. Mass spectroscopy, mutant-based analyses, fluorescence polarization assays, and thermal shift assays revealed 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 new insight into the design of potent and isoform-selective 14-3-3 modulators.<br /> (© 2024 Wiley-VCH GmbH.)

Subjects :: Arabidopsis Proteins antagonists & inhibitors
Arabidopsis Proteins metabolism
Arabidopsis Proteins chemistry
Small Molecule Libraries chemistry
Small Molecule Libraries pharmacology
Small Molecule Libraries metabolism
Molecular Structure
Drug Discovery
Plant Leaves chemistry
Plant Leaves metabolism
14-3-3 Proteins metabolism
14-3-3 Proteins antagonists & inhibitors
14-3-3 Proteins chemistry
Arabidopsis metabolism
Arabidopsis drug effects
Protein Isoforms antagonists & inhibitors
Protein Isoforms metabolism

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