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Eduardo Aranda - One of the best experts on this subject based on the ideXlab platform.
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insect growth regulatory effects of some extracts and sterols from myrtillocactus geometrizans cactaceae against spodoptera frugiperda and tenebrio molitor
Phytochemistry, 2005Co-Authors: Carlos L Cespedes, Rodrigo J Salazar, Mariano Martinez, Eduardo ArandaAbstract:Abstract A methanol extract from the roots and aerial parts of Myrtillocactus geometrizans (Cactaceae) yielded peniocerol 1 , macdougallin 2 , and chichipegenin 3 . The natural products 1 , 2 their mixtures, MeOH and CH 2 Cl 2 extracts showed insecticidal and insect growth regulatory activity against fall armyworm [ Spodoptera frugiperda J. E. Smith (Lepidoptera: Noctuidae)], an important insect pest of corn, and [ Tenebrio molitor (Coleoptera)], a pest of stored grains in Mexico. The most active compounds were 1 , 2 , and a mixture ( M 2 ) of 1 and 2 (6:4). All these extracts, compounds and the mixture had insect growth regulating (IGR) activity between 5.0 and 50.0 ppm and insecticidal effects between 50 and 300 ppm in diets. The extracts were insecticidal to larvae, with lethal doses between 100 and 200 ppm. These compounds appear to have selective effects on the pre-emergence metabolism of Coleoptera, because in all treatments of the larvae of T. molitor , pupation were shortened and this process show precociousness in relation to controls. In contrast to S. frugiperda larvae, onset of pupation was noticeably delayed. Emergence in both cases was drastically diminished. In both pupae and in the few adults that were able to emerge, many deformations were observed. The results of these assays indicated that the compounds were more active than other known natural insect growth inhibitors such as Gedunin and methanol extracts of Cedrela salvadorensis and Yucca periculosa . Peniocerol, macdougallin and chichipegenin, as well as mixtures of these substances, may be useful as natural insecticidal agents.
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insect growth inhibition by tocotrienols and hydroquinones from roldana barba johannis
Phytochemistry, 2004Co-Authors: Carlos L Cespedes, Patricio Torres, Juan C Marin, Amira Arciniegas, Alfonso Romo De Vivar, Ana L Perezcastorena, Eduardo ArandaAbstract:The methanol extract from the aerial parts of Roldana barba-johannis (Asteraceae) afforded sargachromenol, sargahydroquinoic acid, and sargaquinoic acid. These natural products and their corresponding acetylated and methylated derivatives showed insecticidal and insect growth regulatory activities against the Fall Armyworm [Spodoptera frugiperda J.E. Smith, (Lepidoptera: Noctuidae)], an important insect pest of corn. The most active compounds were sargachromenol and its acetylated derivative; sargahydroquinoic acid and its acetylated derivative; and a mixture of sargachromenol, sargahydroquinoic acid, and sargaquinoic acid (6:3:1) and the acetylated form of this mixture. All these compounds and mixtures had significant inhibitory effects between 5.0 and 20.0 ppm in diets. Most compounds were insecticidal to larvae, with lethal doses between 20 and 35 ppm. In addition, these substances also demonstrated scavenging properties toward 2,2-diphenyl-1-picrylhydrazyl radical in TLC autographic and spectrophotometric assays. These compounds appear to have selective effects on the pre-emergence metabolism of the insect. The results from these compounds were fully comparable in activity to those known natural insect growth inhibitors such as Gedunin and methanol extracts of Cedrela salvadorensis and Yucca periculosa. These substances may be useful as natural insecticidal agents.
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antioxidant and insect growth regulatory activities of stilbenes and extracts from yucca periculosa
Phytochemistry, 2003Co-Authors: Patricio Torres, Eduardo Aranda, Juan C Marin, Alfonso Romo De Vivar, Guillermo J Avila, A M Garcia, Carlos L CespedesAbstract:Abstract The methanol extract from the bark of Yucca periculosa F. Baker afforded 4,4′-dihydroxstilbene, resveratrol and 3,3′,5,5′-tetrahydroxy-4-methoxystilbene and had growth regulatory activity against the Fall Army worm ( Spodoptera frugiperda J.E. Smith, Lepidoptera:Noctuidae) an insect pest of corn. The most active compound was 3,3′,5,5′-tetrahydroxy-4-methoxystilbene which had significant effects at 3 μg/g in diets. In addition to the inhibitory activity on bleaching of crocin induced by alkoxyl radicals, these compounds also demonstrated scavenging properties toward 2,2-diphenyl-1-picrylhydrazyl in TLC autographic and spectrophotometric assays. Our results indicate that these compounds could be involved in interference of sclerotization and moulting. These compounds appear to have selective effects on the pre-emergence metabolism of the insect. The results were fully comparable to known natural insect growth inhibitors such as Gedunin and Cedrela extracts and have had a possible role as natural insecticidal agents.
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acetylcholinesterase and insect growth inhibitory activities of gutierrezia microcephala on fall armyworm spodoptera frugiperda j e smith
Zeitschrift für Naturforschung C, 2001Co-Authors: Jose S Calderon, Carlos L Cespedes, Laura Lina, Eduardo Aranda, Juan R Salazar, Rosaura Rosas, Federico Gomezgaribay, Isao KuboAbstract:From the aerial parts of Gutierrezia microcephala (Asteraceae), four oxyflavones were isolated, namely 5,7,2'-trihydroxy-3,6,8,4',5'-pentamethoxyflavone (1); 5,7,4'-trihydroxy-3,6,8-trimethoxyflavone (2); 5,7,2',4'-tetrahydroxy-3,6,8,5'-tetramethoxyflavone (3); 5,2'-dihydroxy-3,6,7,8,4',5'-hexamethoxyflavone (4), and an ent-clerodane, bacchabolivic acid (5). Compounds 1-5, the synthetic methyl ester (6), n-hexane and MeOH extracts were evaluated against the fall armyworm (Spodoptera frugiperda). Gedunin, a known insect growth regulator isolated from Cedrela spp. was used as a positive control. When tested for activity on neonate larvae into the no-choice artificial diet bioassay, flavone (1), clerodane (5), its methyl ester (6), MeOH and n-hexane extracts caused significant larval mortality with MC50 of 3.9, 10.7, 3.46, 7.95 and 7.5 ppm at 7 days, respectively, as well as growth reduction. They also increased the development time of surviving larvae and a significant delay in time to pupation and adult emergence. Acute toxicity against adults of S. frugiperda was also found, 5, 6, Gedunin and n-hexane extract had the most potent activity with LD50 value of 6.59, 15.05, 10.78, and 12.79 ppm, respectively. In addition, MeOH, n-hexane extracts, 5, 6 and Gedunin caused acetylcholinesterase inhibition with 93.7, 100, 90.2, 62.0 and 100% at 50.0 ppm, respectively; whereas 1-4 exhibited only moderate inhibitory activity. Compounds 1, 5 and 6 showed inhibitory activities comparable with Gedunin. These compounds could be responsible of the insect growth inhibitory activity of this plant.
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acetylcholinesterase and insect growth inhibitory activities of gutierrezia microcephala on fall army worm spodoptera frugiperda j e smith
Zeitschrift für Naturforschung C, 2001Co-Authors: Jose S Calderon, Carlos L Cespedes, Laura Lina, Eduardo Aranda, Juan R Salazar, Rosaura Rosas, Federico Gomezgaribay, Isao KuboAbstract:: From the aerial parts of Gutierrezia microcephala (Asteraceae), four oxyflavones were isolated, namely 5,7,2'-trihydroxy-3,6,8,4',5'-pentamethoxyflavone (1); 5,7,4'-trihydroxy-3,6,8-trimethoxyflavone (2); 5,7,2',4'-tetrahydroxy-3,6,8,5'-tetramethoxyflavone (3); 5,2'-dihydroxy-3,6,7,8,4',5'-hexamethoxyflavone (4), and an ent-clerodane, bacchabolivic acid (5). Compounds 1-5, the synthetic methyl ester (6), n-hexane and MeOH extracts were evaluated against the fall armyworm (Spodoptera frugiperda). Gedunin, a known insect growth regulator isolated from Cedrela spp. was used as a positive control. When tested for activity on neonate larvae into the no-choice artificial diet bioassay, flavone (1), clerodane (5), its methyl ester (6), MeOH and n-hexane extracts caused significant larval mortality with MC50 of 3.9, 10.7, 3.46, 7.95 and 7.5 ppm at 7 days, respectively, as well as growth reduction. They also increased the development time of surviving larvae and a significant delay in time to pupation and adult emergence. Acute toxicity against adults of S. frugiperda was also found, 5, 6, Gedunin and n-hexane extract had the most potent activity with LD50 value of 6.59, 15.05, 10.78, and 12.79 ppm, respectively. In addition, MeOH, n-hexane extracts, 5, 6 and Gedunin caused acetylcholinesterase inhibition with 93.7, 100, 90.2, 62.0 and 100% at 50.0 ppm, respectively; whereas 1-4 exhibited only moderate inhibitory activity. Compounds 1, 5 and 6 showed inhibitory activities comparable with Gedunin. These compounds could be responsible of the insect growth inhibitory activity of this plant.
Carlos L Cespedes - One of the best experts on this subject based on the ideXlab platform.
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calceolaria integrifolia s l complex reduces feeding and growth of acanthoscelides obtectus and epilachna varivestis a new source of bioactive compounds against dry bean pests
Industrial Crops and Products, 2016Co-Authors: Carlos L Cespedes, Laura Linagarcia, Isao Kubo, Juan R Salazar, Armando Arizacastolo, Julio Alarcon, Pedro Aqueveque, Enrique Werner, David S SeiglerAbstract:Abstract Acanthoscelides obtectus Say (Coleoptera:Chrysomelidae) and Epilachna varivestis Mulsant (Coleoptera:Coccinellidae) are important predators of dry beans. Due to infestation during crop and storage, these insects affects the quality of seed and crop yields. This study aimed to investigate the effects of samples isolated from Calceolaria integrifolia sensu lato complex aerial parts, on A. obtectus and E. varivestis adults and larval development, respectively. The aerial parts of selected specimens of C. integrifolia s.l. Ehrhart complex (Calceolariaceae), C. integrifolia, C. talcana, C. andina , and the hybrid C. integrifolia x C. talcana were studied as insect growth regulators against dry bean insect pests. In addition to extracts and fractions, some mixtures of compounds were evaluated against the dry bean weevil ( A. obtectus ), and Mexican bean beetle ( E. varivestis ). Neem extract (with azadirachtin), Gedunin, a known insect growth regulator isolated from Cedrela spp., Cedrela extract, some naphthoquinones and Malathion were used as positive controls. When tested for mortality on neonate larvae in a contact artificial diet bioassay, many samples, especially fractions of diterpenes, triterpenes and phenolic compounds, together with n -hexane and ethyl acetate extracts, at 500 μg/cm 2 caused significant mortality with 40–81% against A. obtectus and with 35.0–88.9% against E. varivestis , respectively. At lower concentrations, these substances exhibited growth reduction effects, such as strong repellency effects. They increased the development time of surviving larvae and a significant delay in time to pupation and adult emergence. Acute toxicity against larvae of E. varivestis was also found. In addition to n -hexane extract of C. andina and the hybrid ( C. integrifolia x C. talcana ), those fractions rich in diterpenes, quinones (mixture M5 ), azadirachtin, Gedunin, Cedrela -MeOH-extract, juglone, plumbagin, 1,4-naphthoquinone and Malathion had the most potent lethal effect with values up to 79.0–100% at 500 μg/cm 2 . In addition, fractions of these plants rich in triterpenes and flavonoids caused inhibition of growth at the same concentrations, whereas at minor concentrations they exhibited only moderate inhibitory activity. Many of samples assayed in this study had inhibitory activity comparable to Gedunin and azadirachtin, which were used as positive controls. These results indicate that Calceolaria compounds may serve as desirable tools for protecting stored dry beans against A. obtectus and E. varivestis in small storage facilities as a component of environmentally friendly pest control strategies. Our work supports the use of extracts from C. species both as fumigants, repellent and contact bioinsecticides against stored product pests for crops of economic importance.
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insect growth regulatory effects of some extracts and sterols from myrtillocactus geometrizans cactaceae against spodoptera frugiperda and tenebrio molitor
Phytochemistry, 2005Co-Authors: Carlos L Cespedes, Rodrigo J Salazar, Mariano Martinez, Eduardo ArandaAbstract:Abstract A methanol extract from the roots and aerial parts of Myrtillocactus geometrizans (Cactaceae) yielded peniocerol 1 , macdougallin 2 , and chichipegenin 3 . The natural products 1 , 2 their mixtures, MeOH and CH 2 Cl 2 extracts showed insecticidal and insect growth regulatory activity against fall armyworm [ Spodoptera frugiperda J. E. Smith (Lepidoptera: Noctuidae)], an important insect pest of corn, and [ Tenebrio molitor (Coleoptera)], a pest of stored grains in Mexico. The most active compounds were 1 , 2 , and a mixture ( M 2 ) of 1 and 2 (6:4). All these extracts, compounds and the mixture had insect growth regulating (IGR) activity between 5.0 and 50.0 ppm and insecticidal effects between 50 and 300 ppm in diets. The extracts were insecticidal to larvae, with lethal doses between 100 and 200 ppm. These compounds appear to have selective effects on the pre-emergence metabolism of Coleoptera, because in all treatments of the larvae of T. molitor , pupation were shortened and this process show precociousness in relation to controls. In contrast to S. frugiperda larvae, onset of pupation was noticeably delayed. Emergence in both cases was drastically diminished. In both pupae and in the few adults that were able to emerge, many deformations were observed. The results of these assays indicated that the compounds were more active than other known natural insect growth inhibitors such as Gedunin and methanol extracts of Cedrela salvadorensis and Yucca periculosa . Peniocerol, macdougallin and chichipegenin, as well as mixtures of these substances, may be useful as natural insecticidal agents.
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insect growth inhibition by tocotrienols and hydroquinones from roldana barba johannis
Phytochemistry, 2004Co-Authors: Carlos L Cespedes, Patricio Torres, Juan C Marin, Amira Arciniegas, Alfonso Romo De Vivar, Ana L Perezcastorena, Eduardo ArandaAbstract:The methanol extract from the aerial parts of Roldana barba-johannis (Asteraceae) afforded sargachromenol, sargahydroquinoic acid, and sargaquinoic acid. These natural products and their corresponding acetylated and methylated derivatives showed insecticidal and insect growth regulatory activities against the Fall Armyworm [Spodoptera frugiperda J.E. Smith, (Lepidoptera: Noctuidae)], an important insect pest of corn. The most active compounds were sargachromenol and its acetylated derivative; sargahydroquinoic acid and its acetylated derivative; and a mixture of sargachromenol, sargahydroquinoic acid, and sargaquinoic acid (6:3:1) and the acetylated form of this mixture. All these compounds and mixtures had significant inhibitory effects between 5.0 and 20.0 ppm in diets. Most compounds were insecticidal to larvae, with lethal doses between 20 and 35 ppm. In addition, these substances also demonstrated scavenging properties toward 2,2-diphenyl-1-picrylhydrazyl radical in TLC autographic and spectrophotometric assays. These compounds appear to have selective effects on the pre-emergence metabolism of the insect. The results from these compounds were fully comparable in activity to those known natural insect growth inhibitors such as Gedunin and methanol extracts of Cedrela salvadorensis and Yucca periculosa. These substances may be useful as natural insecticidal agents.
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antioxidant and insect growth regulatory activities of stilbenes and extracts from yucca periculosa
Phytochemistry, 2003Co-Authors: Patricio Torres, Eduardo Aranda, Juan C Marin, Alfonso Romo De Vivar, Guillermo J Avila, A M Garcia, Carlos L CespedesAbstract:Abstract The methanol extract from the bark of Yucca periculosa F. Baker afforded 4,4′-dihydroxstilbene, resveratrol and 3,3′,5,5′-tetrahydroxy-4-methoxystilbene and had growth regulatory activity against the Fall Army worm ( Spodoptera frugiperda J.E. Smith, Lepidoptera:Noctuidae) an insect pest of corn. The most active compound was 3,3′,5,5′-tetrahydroxy-4-methoxystilbene which had significant effects at 3 μg/g in diets. In addition to the inhibitory activity on bleaching of crocin induced by alkoxyl radicals, these compounds also demonstrated scavenging properties toward 2,2-diphenyl-1-picrylhydrazyl in TLC autographic and spectrophotometric assays. Our results indicate that these compounds could be involved in interference of sclerotization and moulting. These compounds appear to have selective effects on the pre-emergence metabolism of the insect. The results were fully comparable to known natural insect growth inhibitors such as Gedunin and Cedrela extracts and have had a possible role as natural insecticidal agents.
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acetylcholinesterase and insect growth inhibitory activities of gutierrezia microcephala on fall armyworm spodoptera frugiperda j e smith
Zeitschrift für Naturforschung C, 2001Co-Authors: Jose S Calderon, Carlos L Cespedes, Laura Lina, Eduardo Aranda, Juan R Salazar, Rosaura Rosas, Federico Gomezgaribay, Isao KuboAbstract:From the aerial parts of Gutierrezia microcephala (Asteraceae), four oxyflavones were isolated, namely 5,7,2'-trihydroxy-3,6,8,4',5'-pentamethoxyflavone (1); 5,7,4'-trihydroxy-3,6,8-trimethoxyflavone (2); 5,7,2',4'-tetrahydroxy-3,6,8,5'-tetramethoxyflavone (3); 5,2'-dihydroxy-3,6,7,8,4',5'-hexamethoxyflavone (4), and an ent-clerodane, bacchabolivic acid (5). Compounds 1-5, the synthetic methyl ester (6), n-hexane and MeOH extracts were evaluated against the fall armyworm (Spodoptera frugiperda). Gedunin, a known insect growth regulator isolated from Cedrela spp. was used as a positive control. When tested for activity on neonate larvae into the no-choice artificial diet bioassay, flavone (1), clerodane (5), its methyl ester (6), MeOH and n-hexane extracts caused significant larval mortality with MC50 of 3.9, 10.7, 3.46, 7.95 and 7.5 ppm at 7 days, respectively, as well as growth reduction. They also increased the development time of surviving larvae and a significant delay in time to pupation and adult emergence. Acute toxicity against adults of S. frugiperda was also found, 5, 6, Gedunin and n-hexane extract had the most potent activity with LD50 value of 6.59, 15.05, 10.78, and 12.79 ppm, respectively. In addition, MeOH, n-hexane extracts, 5, 6 and Gedunin caused acetylcholinesterase inhibition with 93.7, 100, 90.2, 62.0 and 100% at 50.0 ppm, respectively; whereas 1-4 exhibited only moderate inhibitory activity. Compounds 1, 5 and 6 showed inhibitory activities comparable with Gedunin. These compounds could be responsible of the insect growth inhibitory activity of this plant.
Sengottayan Senthil Nathan - One of the best experts on this subject based on the ideXlab platform.
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effects of neem limonoids on the malaria vector anopheles stephensi liston diptera culicidae
Acta Tropica, 2005Co-Authors: Sengottayan Senthil Nathan, Kandaswamy Kalaivani, Kadarkarai MuruganAbstract:The effects of the neem (Azadirachta indica A. Juss) limonoids azadirachtin, salannin, deacetylGedunin, Gedunin, 17-hydroxyazadiradione and deacetylnimbin on Anopheles stephensi Liston (Diptera: Culicidae) were investigated. In exploring advantages of pure neem limonoids, we studied the larvicidal, pupicidal, adulticidal and antiovipositional activity of neem limonoids. Azadirachtin, salannin and deacetylGedunin showed high bioactivity at all doses, while the rest of the neem limonoids were less active, and were only biologically active at high doses. Azadirachtin was the most potent in all experiments and produced almost 100% larval mortality at 1 ppm concentration. In general, first to third larval instars were more susceptible to the neem limonoids. Neem products may have benefits in mosquito control programs.
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efficacy of neem limonoids on cnaphalocrocis medinalis guenee lepidoptera pyralidae the rice leaffolder
Crop Protection, 2005Co-Authors: Sengottayan Senthil Nathan, Kandaswamy Kalaivani, Kadarkarai Murugan, Paul Gene ChungAbstract:Abstract In leaf cut choice assay and topical application experiments, the neem (Azadirachta indica) limonoids azadirachtin, salannin, deacetylGedunin, Gedunin, 17-hydroxyazadiradione, and deacetylnimbin showed strong antifeedant and growth inhibitor activity against fifth instar larvae of Cnaphalocrocis medinalis, the rice leaffolder, a serious pest of rice in Asian countries. The parameters, used to evaluate the activity of the limonoids were larval food utilization, quantity of ingested and digested food; consumption index and feeding deterrence index. Azadirachtin, salannin, deacetylGedunin showed high bioactivity at all doses, while the other neem limonoids proved to be less active, and only at the higher doses did they display antifeedant activity. Azadirachtin was the most potent in all experiments. Gross dietary utilization (efficiency of conversion of ingested food) of C. medinalis was also decreased after treatment with limonoids. Our results suggest that neem limonoids may be used in IPM programs for rice leaffolder and should be evaluated for efficacy under field conditions.
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the toxicity and physiological effect of neem limonoids on cnaphalocrocis medinalis guenee the rice leaffolder
Pesticide Biochemistry and Physiology, 2005Co-Authors: Sengottayan Senthil Nathan, Kandaswamy Kalaivani, Kadarkarai Murugan, Paul Gene ChungAbstract:Abstract The effect of neem ( Azadirachta indica ) limonoids azadirachtin, salannin, deacetylGedunin, Gedunin, 17-hydroxyazadiradione, and deaceytlnimbin on gut enzyme activity of the rice leaffolder larvae was investigated. When fed a diet of rice leaves treated with limonoids in bioassays, gut tissue enzymes—acid phosphatases (ACP), alkaline phosphatases (ALP), and adenosine triphosphatases (ATPase) activities of rice leaffolder ( Cnaphalocrocis medinalis ) larvae are affected. Azadirachtin was most potent in all experiments. Larvae that were chronically exposed to limonoids showed a reduction in weight (59–89%) and exhibited a significant reduction in ACP, ALP, and ATPase activities. These results indicate neem limonoids affects gut enzyme activities. These effects are most pronounced in early instars.
Ernst Schonbrunn - One of the best experts on this subject based on the ideXlab platform.
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Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of
2016Co-Authors: S H Olesen, Donna J Ingles, J Y Zhu, M P Martin, S Betzi, Gunda I Georg, Joseph S Tash, Ernst SchonbrunnAbstract:The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in-vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors Gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution licens
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stability of the human hsp90 p50cdc37 chaperone complex against nucleotides and hsp90 inhibitors and the influence of phosphorylation by casein kinase 2
Molecules, 2015Co-Authors: S H Olesen, Donna J Ingles, J Y Zhu, M P Martin, S Betzi, Gunda I Georg, Joseph S Tash, Ernst SchonbrunnAbstract:The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors Gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands.
S H Olesen - One of the best experts on this subject based on the ideXlab platform.
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Stability of the Human Hsp90-p50Cdc37 Chaperone Complex against Nucleotides and Hsp90 Inhibitors, and the Influence of
2016Co-Authors: S H Olesen, Donna J Ingles, J Y Zhu, M P Martin, S Betzi, Gunda I Georg, Joseph S Tash, Ernst SchonbrunnAbstract:The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in-vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors Gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution licens
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stability of the human hsp90 p50cdc37 chaperone complex against nucleotides and hsp90 inhibitors and the influence of phosphorylation by casein kinase 2
Molecules, 2015Co-Authors: S H Olesen, Donna J Ingles, J Y Zhu, M P Martin, S Betzi, Gunda I Georg, Joseph S Tash, Ernst SchonbrunnAbstract:The molecular chaperone Hsp90 is regulated by co-chaperones such as p50Cdc37, which recruits a wide selection of client protein kinases. Targeted disruption of the Hsp90-p50Cdc37 complex by protein-protein interaction (PPI) inhibitors has emerged as an alternative strategy to treat diseases characterized by aberrant Hsp90 activity. Using isothermal microcalorimetry, ELISA and GST-pull down assays we evaluated reported Hsp90 inhibitors and nucleotides for their ability to inhibit formation of the human Hsp90β-p50Cdc37 complex, reconstituted in vitro from full-length proteins. Hsp90 inhibitors, including the proposed PPI inhibitors Gedunin and H2-gamendazole, did not affect the interaction of Hsp90 with p50Cdc37 in vitro. Phosphorylation of Hsp90 and p50Cdc37 by casein kinase 2 (CK2) did not alter the thermodynamic signature of complex formation. However, the phosphorylated complex was vulnerable to disruption by ADP (IC50 = 32 µM), while ATP, AMPPNP and Hsp90 inhibitors remained largely ineffective. The differential inhibitory activity of ADP suggests that phosphorylation by CK2 primes the complex for dissociation in response to a drop in ATP/ADP levels. The approach applied herein provides robust assays for a comprehensive biochemical evaluation of potential effectors of the Hsp90-p50Cdc37 complex, such as phosphorylation by a kinase or the interaction with small molecule ligands.
