A series of(R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfur ether moiety were synthesized and characterized on the basis of NMR and elemental analysis(EA). The crystal structure of(R)-N-(...A series of(R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfur ether moiety were synthesized and characterized on the basis of NMR and elemental analysis(EA). The crystal structure of(R)-N-(2-methyl-1-(methylthio)propan-2-yl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carboxamide(13 d) was determined to show R configuration. The bioasssy results indicated that most title compounds displayed good and broad spectrum antifungal activities against several phytopathogenic fungi. The structure activity relationships were discussed. Based on the antifungal activity of title compounds against Phytophthora capsici, a CoMSIA calculation was performed to establish a 3 D-QSAR model, which revealed that electrostatic and hydrophobic fields were the two most significant factors for antifungal activity. According to the established 3D-QSAR model, structure optimization was carried out to find(R)-N-((R)-1-(methylthio)propan-2-yl)-2-(p-tolyl)-4,5-dihydrothiazole-4-carboxamide(15 h)with excellent activity against Phytophthora capsici, thus emerging as a new lead compound for novel antiphytopathogenic fungus agent development.展开更多
Pattern recognition receptors(PRRs)sense ligands in pattern-triggered immunity(PTI).Plant PRRs include numerous receptor-like proteins(RLPs),but many RLPs remain functionally uncharacterized.Here,we examine an Arabido...Pattern recognition receptors(PRRs)sense ligands in pattern-triggered immunity(PTI).Plant PRRs include numerous receptor-like proteins(RLPs),but many RLPs remain functionally uncharacterized.Here,we examine an Arabidopsis thaliana RLP,RLP53,which positively regulates immune signaling.Our forward genetic screen for suppressors of enhanced disease resistance1(edr1)identified a point mutation in RLP53 that fully suppresses disease resistance and mildewinduced cell death in edr1 mutants.The rlp53 mutants showed enhanced susceptibility to virulent pathogens,including fungi,oomycetes,and bacteria,indicating that RLP53 is important for plant immunity.The ectodomain of RLP53 contains leucine-rich repeat(LRR)motifs.RLP53 constitutively associates with the LRR receptorlike kinase SUPPRESSOR OF BRASSINOSTEROIDINSENSITIVE1-ASSOCIATEDKINASE(BAK1)-INTERACTINGRECEPTORKINASE1(SOBIR1)and interacts with the co-receptor BAK1 in a pathogen-induced manner.The double mutation sobir1-12 bak1-5 suppresses edr1-mediated disease resistance,suggesting that EDR1 negatively regulates PTI modulated by the RLP53–SOBIR1–BAK1 complex.Moreover,the glycosylphosphatidylinositol(GPI)-anchored protein LORELEI-LIKE GPI-ANCHORED PROTEIN1(LLG1)interacts with RLP53 and mediates RLP53 accumulation in the plasma membrane.We thus uncovered the role of a novel RLP and its associated immune complex in plant defense responses and revealed a potential new mechanism underlying regulation of RLP immune function by a GPI-anchored protein.展开更多
Mitogen-activated protein kinase(MAPK) cascades are highly conserved signaling modules that regulate plant immune responses. The Arabidopsis thaliana Raf-like MAPK kinase kinase ENHANCED DISEASE RESISTANCE1(EDR1) is a...Mitogen-activated protein kinase(MAPK) cascades are highly conserved signaling modules that regulate plant immune responses. The Arabidopsis thaliana Raf-like MAPK kinase kinase ENHANCED DISEASE RESISTANCE1(EDR1) is a key negative regulator of plant immunity that affects the protein levels of MKK4 and MKK5, two important MAPK cascade members, but the underlying mechanism is poorly understood. Here, genome-wide phosphorylation analysis demonstrated that the E3 ligase KEEP ON GOING(KEG) is phosphorylated in the edr1 mutant but not the wild type, suggesting that EDR1 negatively affects KEG phosphorylation. The identified phosphorylation sites in KEG appear to be important for its accumulation. The keg-4 mutant, a previously identified edr1 suppressor, enhances susceptibility to the powdery mildew pathogen Golovinomyces cichoracearum. In addition, MKK4 and MKK5 protein levels are reduced in the keg-4 mutant. Furthermore,we demonstrate that MKK4 and MKK5 associate with full-length KEG, but not with truncated KEG-RK or KEG-RKA, and that KEG ubiquitinates and mediates the degradation of MKK4 and MKK5. Taken together, these results indicate that MKK4 and MKK5 protein levels are regulated by KEG via ubiquitination, uncovering a mechanism by which plants finetune immune responses by regulating the homeostasis of key MAPK cascade members via ubiquitination and degradation.展开更多
To search for potent insecticides targeting at ryanodine receptors(RyRs),a series of novel anthranilic diamides analogs containing 4-chlorine N-pyridylpyrazole were designed and synthesized.Their insecticidal activiti...To search for potent insecticides targeting at ryanodine receptors(RyRs),a series of novel anthranilic diamides analogs containing 4-chlorine N-pyridylpyrazole were designed and synthesized.Their insecticidal activities were evaluated and the preliminary struc ture-activity relationships(SARs)were discussed.The insecticidal results showed that some of the compounds(8a-8h,8m,8n)exhibited good larvicidal activities against oriental armyworm at 2.5 mg·L^(-1),and compound 8m possessed 60%insecticidal activityat 0.5 mg·L^(-1).For diamondback moth,8m exhibited better activity than Chlorantraniliprole at a hundred fold preference.展开更多
基金financially supported by the Scientific Project of Tianjin Municipal Education Commission(No. 2018KJ008)Tianjin Natural Science Foundation(No. 16JCYBJC29400)
文摘A series of(R)-2-phenyl-4,5-dihydrothiazole-4-carboxamide derivatives containing a sulfur ether moiety were synthesized and characterized on the basis of NMR and elemental analysis(EA). The crystal structure of(R)-N-(2-methyl-1-(methylthio)propan-2-yl)-2-(4-nitrophenyl)-4,5-dihydrothiazole-4-carboxamide(13 d) was determined to show R configuration. The bioasssy results indicated that most title compounds displayed good and broad spectrum antifungal activities against several phytopathogenic fungi. The structure activity relationships were discussed. Based on the antifungal activity of title compounds against Phytophthora capsici, a CoMSIA calculation was performed to establish a 3 D-QSAR model, which revealed that electrostatic and hydrophobic fields were the two most significant factors for antifungal activity. According to the established 3D-QSAR model, structure optimization was carried out to find(R)-N-((R)-1-(methylthio)propan-2-yl)-2-(p-tolyl)-4,5-dihydrothiazole-4-carboxamide(15 h)with excellent activity against Phytophthora capsici, thus emerging as a new lead compound for novel antiphytopathogenic fungus agent development.
基金supported by grants from the National Natural Science Foundation of China(32161133012 and 31830077)to D.T.
文摘Pattern recognition receptors(PRRs)sense ligands in pattern-triggered immunity(PTI).Plant PRRs include numerous receptor-like proteins(RLPs),but many RLPs remain functionally uncharacterized.Here,we examine an Arabidopsis thaliana RLP,RLP53,which positively regulates immune signaling.Our forward genetic screen for suppressors of enhanced disease resistance1(edr1)identified a point mutation in RLP53 that fully suppresses disease resistance and mildewinduced cell death in edr1 mutants.The rlp53 mutants showed enhanced susceptibility to virulent pathogens,including fungi,oomycetes,and bacteria,indicating that RLP53 is important for plant immunity.The ectodomain of RLP53 contains leucine-rich repeat(LRR)motifs.RLP53 constitutively associates with the LRR receptorlike kinase SUPPRESSOR OF BRASSINOSTEROIDINSENSITIVE1-ASSOCIATEDKINASE(BAK1)-INTERACTINGRECEPTORKINASE1(SOBIR1)and interacts with the co-receptor BAK1 in a pathogen-induced manner.The double mutation sobir1-12 bak1-5 suppresses edr1-mediated disease resistance,suggesting that EDR1 negatively regulates PTI modulated by the RLP53–SOBIR1–BAK1 complex.Moreover,the glycosylphosphatidylinositol(GPI)-anchored protein LORELEI-LIKE GPI-ANCHORED PROTEIN1(LLG1)interacts with RLP53 and mediates RLP53 accumulation in the plasma membrane.We thus uncovered the role of a novel RLP and its associated immune complex in plant defense responses and revealed a potential new mechanism underlying regulation of RLP immune function by a GPI-anchored protein.
基金supported by grants from the National Natural Science Foundation of China (31761133017 and 31525019) to D.T。
文摘Mitogen-activated protein kinase(MAPK) cascades are highly conserved signaling modules that regulate plant immune responses. The Arabidopsis thaliana Raf-like MAPK kinase kinase ENHANCED DISEASE RESISTANCE1(EDR1) is a key negative regulator of plant immunity that affects the protein levels of MKK4 and MKK5, two important MAPK cascade members, but the underlying mechanism is poorly understood. Here, genome-wide phosphorylation analysis demonstrated that the E3 ligase KEEP ON GOING(KEG) is phosphorylated in the edr1 mutant but not the wild type, suggesting that EDR1 negatively affects KEG phosphorylation. The identified phosphorylation sites in KEG appear to be important for its accumulation. The keg-4 mutant, a previously identified edr1 suppressor, enhances susceptibility to the powdery mildew pathogen Golovinomyces cichoracearum. In addition, MKK4 and MKK5 protein levels are reduced in the keg-4 mutant. Furthermore,we demonstrate that MKK4 and MKK5 associate with full-length KEG, but not with truncated KEG-RK or KEG-RKA, and that KEG ubiquitinates and mediates the degradation of MKK4 and MKK5. Taken together, these results indicate that MKK4 and MKK5 protein levels are regulated by KEG via ubiquitination, uncovering a mechanism by which plants finetune immune responses by regulating the homeostasis of key MAPK cascade members via ubiquitination and degradation.
基金The project was supported by the National Key Research Program-The Innovation of Eco-Modulator of Insect Ryanodine Re-ceptor(Nos.2018YFD0200100,2017YFD0200505)the National Natural Science Foundation of China(Nos.31972287,21602118).
文摘To search for potent insecticides targeting at ryanodine receptors(RyRs),a series of novel anthranilic diamides analogs containing 4-chlorine N-pyridylpyrazole were designed and synthesized.Their insecticidal activities were evaluated and the preliminary struc ture-activity relationships(SARs)were discussed.The insecticidal results showed that some of the compounds(8a-8h,8m,8n)exhibited good larvicidal activities against oriental armyworm at 2.5 mg·L^(-1),and compound 8m possessed 60%insecticidal activityat 0.5 mg·L^(-1).For diamondback moth,8m exhibited better activity than Chlorantraniliprole at a hundred fold preference.
