Synthesis and reactions of some 5(6)-(1-adamantyl)benzimidazoles

Zurabishvili, D. S.; Lomidze, M. O.; Samsoniya, Sh. A.; Wesquet, Alexander O.; Kazmaier, Uli

doi:10.1007/s10593-008-0136-z

Cited by 4 publications

(1 citation statement)

References 7 publications

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“…5-Adamantyl-IAA (21) was synthesized in a similar manner to 15 (Scheme 2). Acetanilide ( 22) was treated with 1-bromoadamantane in the presence of zinc chloride to give 23 (Zurabishvili et al 2008). The iodination of 23, followed by Sonogashira-Hagihara coupling and deprotection, afforded 5adamantyl indole (26).…”

Section: Iaas With Non-aromatic Substitutionsmentioning

confidence: 99%

A Super Strong Engineered Auxin–TIR1 Pair

Yamada

Murai

Uchida

et al. 2018

Plant and Cell Physiology

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Auxin regulates diverse aspects of plant growth and development through induction of the interaction between TRANSPORT INHIBITOR RESPONSE 1/AUXIN SIGNALING F-BOX proteins (TIR1/AFBs) and AUXIN/INDOLE-3-ACETIC ACID (Aux/IAA) co-receptor proteins and the subsequent transcriptional regulation. The artificial control of endogenous auxin signaling should enable the precise delineation of auxin-mediated biological events as well as the agricultural application of auxin. To this end, we previously developed a synthetic auxin-receptor pair that consists of 5-(3-methoxyphenyl)-IAA (convexIAA, cvxIAA) and the engineered TIR1 whose phenylalanine at position 79 in the auxin-binding pocket is substituted to glycine (TIR1F79G) (concaveTIR1, ccvTIR1). This synthetic auxin-receptor pair works orthogonally to natural auxin signaling in transgenic plants harboring the engineered TIR1 by exogenous application of 5-(3-methoxyphenyl)-IAA, and has potential to be utilized as novel agricultural/horticultural tools. In the present study, we report an improved version of the synthetic cvxIAA-ccvTIR1 pair such that synthetic IAA can act at lower concentrations. Using a yeast two-hybrid system, we screened various 5-substituted IAAs and identified 5-adamantyl-IAA, named pico_cvxIAA, which mediates interaction of TIR1F79G and IAA3 proteins at a 1,000-fold lower concentration than the original version, 5-(3-methoxyphenyl)-IAA. Furthermore, we found that TIR1F79A interacts with IAA3 protein in the presence of picomolar concentrations of 5-adamantyl-IAA, 10,000-fold lower than our prototype version of the cvxIAA-ccvTIR1 pair. In addition, pull-down assays confirmed that 5-adamantyl-IAA mediates in vitro interaction of TIR1F79A and IAA7-DII peptides at lower concentrations. The improved synthetic IAA-TIR1 pair with high affinity would be beneficial for basic science as well as for practical use in agriculture/horticulture.

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Section: Iaas With Non-aromatic Substitutionsmentioning

confidence: 99%

A Super Strong Engineered Auxin–TIR1 Pair

Yamada

Murai

Uchida

et al. 2018

Plant and Cell Physiology

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Development of LM98, a Small‐Molecule TEAD Inhibitor Derived from Flufenamic Acid

et al. 2021

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The YAP-TEAD transcriptional complex is responsible for the expression of genes that regulate cancer cell growth and proliferation. Dysregulation of the Hippo pathway due to overexpression of TEAD has been reported in a wide range of cancers. Inhibition of TEAD represses the expression of associated genes, demonstrating the value of this transcription factor for the development of novel anti-cancer therapies. We report herein the design, synthesis and biological evaluation of LM98, a flufenamic acid analogue. LM98 shows strong affinity to TEAD, inhibits its autopalmitoylation and reduces the YAP-TEAD transcriptional activity. Binding of LM98 to TEAD was supported by 19 F-NMR studies while co-crystallization experiments confirmed that LM98 is anchored within the palmitic acid pocket of TEAD. LM98 reduces the expression of CTGF and Cyr61, inhibits MDA-MB-231 breast cancer cell migration and arrests cell cycling in the S phase during cell division.

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