Bikinin-like inhibitors targeting GSK3/Shaggy-like kinases: characterisation of novel compounds and elucidation of their catabolism in planta

BMC Plant Biology

Research Article

Tingting Chen¹  Brigitte Poppenberger²  Wuyan Wang³  Franz Berthiller⁴  Juliane Mayerhofer⁵  Claudia Jonak⁵  Elena Petutschnig⁶  Wilfried Rozhon⁷  Tobias Sieberer⁸ 

[1] Biotechnology of Horticultural Crops, Technische Universität München, Liesel-Beckmann-Straße 1, 85354, Freising, Germany;Biotechnology of Horticultural Crops, Technische Universität München, Liesel-Beckmann-Straße 1, 85354, Freising, Germany;Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, 1030, Vienna, Austria;Biotechnology of Horticultural Crops, Technische Universität München, Liesel-Beckmann-Straße 1, 85354, Freising, Germany;Plant Biochemistry, ETH Zürich, Universitätsstr. 2, 8092, Zürich, Switzerland;Center for Analytical Chemistry, Department of Agrobiotechnology, University of Natural Resources and Life Sciences, Konrad Lorenz Straße 20, 3430, Tulln, Austria;GMI-Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Vienna Biocenter, Dr. Bohr-Gasse 3, 1030, Vienna, Austria;GMI-Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Vienna Biocenter, Dr. Bohr-Gasse 3, 1030, Vienna, Austria;Albrecht-von-Haller-Institute of Plant Sciences, Department of Plant Cell Biology, Georg-August-University Göttingen, Julia-Lermontowa-Weg 3, 37077, Göttingen, Germany;GMI-Gregor Mendel Institute of Molecular Plant Biology, Austrian Academy of Sciences, Vienna Biocenter, Dr. Bohr-Gasse 3, 1030, Vienna, Austria;Biotechnology of Horticultural Crops, Technische Universität München, Liesel-Beckmann-Straße 1, 85354, Freising, Germany;Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, 1030, Vienna, Austria;Max F. Perutz Laboratories, Department of Microbiology, Immunobiology and Genetics, University of Vienna, 1030, Vienna, Austria;Department of Plant Sciences, Research Unit Plant Growth Regulation, Technische Universität München, Liesel-Beckmann-Straße 1, 85354, Freising-Weihenstephan, Germany;

关键词: Brassinosteroid;    GSK-3/shaggy-like kinase;    Inhibitor;    Protein phosphorylation;    Signal transduction;   

DOI  :  10.1186/1471-2229-14-172

 received in 2014-01-15, accepted in 2014-06-17,  发布年份 2014

来源: Springer

【 摘 要 】

BackgroundPlant GSK-3/Shaggy-like kinases are key players in brassinosteroid (BR) signalling which impact on plant development and participate in response to wounding, pathogens and salt stress. Bikinin was previously identified in a chemical genetics screen as an inhibitor targeting these kinases. To dissect the structural elements crucial for inhibition of GSK-3/Shaggy-like kinases by bikinin and to isolate more potent compounds we synthesised a number of related substances and tested their inhibitory activity in vitro and in vivo using Arabidopsis thaliana.ResultsA pyridine ring with an amido succinic acid residue in position 2 and a halogen in position 5 were crucial for inhibitory activity. The compound with an iodine substituent in position 5, denoted iodobikinin, was most active in inhibiting BIN2 activity in vitro and efficiently induced brassinosteroid-like responses in vivo. Its methyl ester, methyliodobikinin, showed improved cell permeability, making it highly potent in vivo although it had lower activity in vitro. HPLC analysis revealed that the methyl residue was rapidly cleaved off in planta liberating active iodobikinin. In addition, we provide evidence that iodobikinin and bikinin are inactivated in planta by conjugation with glutamic acid or malic acid and that the latter process is catalysed by the malate transferase SNG1.ConclusionBrassinosteroids participate in regulation of many aspects of plant development and in responses to environmental cues. Thus compounds modulating their action are valuable tools to study such processes and may be an interesting opportunity to modify plant growth and performance in horticulture and agronomy. Here we report the development of bikinin derivatives with increased potency that can activate BR signalling and mimic BR action. Methyliodobikinin was 3.4 times more active in vivo than bikinin. The main reason for the superior activity of methyliodobikinin, the most potent compound, is its enhanced plant tissue permeability. Inactivation of bikinin and its derivatives in planta involves SNG1, which constitutes a novel pathway for modification of xenobiotic compounds.

【 授权许可】

CC BY   
© Rozhon et al.; licensee BioMed Central Ltd. 2014