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  • Discovery and characterization of small molecule inhibitors of cystathionine gamma-synthase with in planta activity.

Discovery and characterization of small molecule inhibitors of cystathionine gamma-synthase with in planta activity.

Plant biotechnology journal (2021-03-28)
Itai Bloch, Hadar Haviv, Irena Rapoport, Elad Cohen, Rotem Shelly Ben Shushan, Nesly Dotan, Inbal Sher, Yael Hacham, Rachel Amir, Maayan Gal
ABSTRACT

The synthesis of essential amino acids in plants is pivotal for their viability and growth, and these cellular pathways are therefore targeted for the discovery of new molecules for weed control. Herein, we describe the discovery and design of small molecule inhibitors of cystathionine gamma-synthase, a key enzyme in the biosynthesis of methionine. Based on in silico screening and filtering of a large molecular database followed by the in vitro selection of molecules, we identified small molecules capable of binding the target enzyme. Molecular modelling of the interaction and direct biophysical binding enabled us to explore a focussed chemical expansion set of molecules characterized by an active phenyl-benzamide chemical group. These molecules are bio-active and efficiently inhibit the viability of BY-2 tobacco cells and seedlings growth of Arabidopsis thaliana on agar plates.

MATERIALS
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Brand
Product Description

Sigma-Aldrich
Murashige and Skoog Basal Medium, powder, suitable for plant cell culture, with Gamborg′s vitamins