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

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‐synthas...

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Autores principales: Bloch, Itai, Haviv, Hadar, Rapoport, Irena, Cohen, Elad, Shushan, Rotem Shelly Ben, Dotan, Nesly, Sher, Inbal, Hacham, Yael, Amir, Rachel, Gal, Maayan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428831/
https://www.ncbi.nlm.nih.gov/pubmed/33773037
http://dx.doi.org/10.1111/pbi.13591
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author Bloch, Itai
Haviv, Hadar
Rapoport, Irena
Cohen, Elad
Shushan, Rotem Shelly Ben
Dotan, Nesly
Sher, Inbal
Hacham, Yael
Amir, Rachel
Gal, Maayan
author_facet Bloch, Itai
Haviv, Hadar
Rapoport, Irena
Cohen, Elad
Shushan, Rotem Shelly Ben
Dotan, Nesly
Sher, Inbal
Hacham, Yael
Amir, Rachel
Gal, Maayan
author_sort Bloch, Itai
collection PubMed
description 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.
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spelling pubmed-84288312021-09-14 Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity Bloch, Itai Haviv, Hadar Rapoport, Irena Cohen, Elad Shushan, Rotem Shelly Ben Dotan, Nesly Sher, Inbal Hacham, Yael Amir, Rachel Gal, Maayan Plant Biotechnol J Research Articles 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. John Wiley and Sons Inc. 2021-05-12 2021-09 /pmc/articles/PMC8428831/ /pubmed/33773037 http://dx.doi.org/10.1111/pbi.13591 Text en © 2021 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ (https://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Research Articles
Bloch, Itai
Haviv, Hadar
Rapoport, Irena
Cohen, Elad
Shushan, Rotem Shelly Ben
Dotan, Nesly
Sher, Inbal
Hacham, Yael
Amir, Rachel
Gal, Maayan
Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
title Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
title_full Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
title_fullStr Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
title_full_unstemmed Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
title_short Discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
title_sort discovery and characterization of small molecule inhibitors of cystathionine gamma‐synthase with in planta activity
topic Research Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8428831/
https://www.ncbi.nlm.nih.gov/pubmed/33773037
http://dx.doi.org/10.1111/pbi.13591
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