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In this study, we investigated how the replacement of the tetrahydrothiophene ring of biotin with either an oxolane or (methyl)pyrrolidine moiety may affect its molecular interactions, in an effort to identify alternative affinity ligands suitable for in vitro and in vivo applications in synthetic biology. Initial molecular dynamics (MD) simulations suggested the potential formation of a hydrogen bond between either the oxygen or nitrogen atom of the envisaged tetrahydroheteryl analogues and the Thr90 residue of streptavidin, mirroring the sulfur-centered hydrogen bond detected by the crystallographic analysis of the biotin-streptavidin interaction. Therefore, oxy-, aza-, and N-methylazabiotin were readily synthesized starting from chiral five- or six-carbon sugar precursors. Based on fluorescence-based titration experiments using the corresponding fluorescein conjugates, oxybiotin showed a binding behavior similar to biotin with streptavidin, while both amino analogues displayed lower binding capacities. Notably, azabiotin exhibited a pH-dependent interaction profile, demonstrating enhanced binding under acidic conditions but weaker binding under basic pH, which could be exploited for various purposes.
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Biotina , Estreptavidina , Enxofre , Biotina/química , Estreptavidina/química , Estrutura Molecular , Enxofre/química , Sítios de Ligação , Simulação de Dinâmica Molecular , Ligação Proteica , Ligação de HidrogênioRESUMO
Physicochemical properties between colloidal engineered nanomaterials (ENMs) and aerosols released from consumer spray products were characterized. A dynamic light scattering (DLS), transmission electron microscopy (TEM), and inductively coupled plasma mass spectrometer (ICP-MS) were used to evaluate the suspended ENMs in the products. Direct-reading instruments, TEM, and ICP-MS were used to characterize the properties of aerosolized ENMs. The aerosolized organic compounds with ENMs were assumed to be vaporized for a short time after spraying. The median diameter of ENMs in product solutions measured by DLS was about 200-350 nm, while individual particle was confirmed from 3 to 50 nm by TEM. The size of aerosolized ENMs was ranged from 7 to 44 nm, and their aggregates were about 100-1000 nm in near distance. Some inorganic substances including raw nanomaterials were also found in the aerosol. The particles released from the propellant sprays were identified in far distance, while they were not found in far distance when pump sprays were used. The number concentration from the propellant sprays increased up to 6000 particles/cm3 /g at near distance and dispersed to far distance, while the most of droplets emitted from pump sprays were settled down near sprayer's location. We found other metals besides labeled ENMs are included in each product and the characteristics of the particles are different when they are sprayed.
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Poluição do Ar em Ambientes Fechados/análise , Nanoestruturas/análise , Aerossóis , Poeira , Exposição por Inalação , Tamanho da PartículaRESUMO
A series of nucleotide analogues, with a hypoxanthine base moiety (8-aminohypoxanthine, 1-methyl-8-aminohypoxanthine, and 8-oxohypoxanthine), together with 5-methylisocytosine were tested as potential pairing partners of N8 -glycosylated nucleotides with an 8-azaguanine or 8-aza-9-deazaguanine base moiety by using DNA polymerases (incorporation studies). The best results were obtained with the 5-methylisocytosine nucleotide followed by the 1-methyl-8-aminohypoxanthine nucleotide. The experiments demonstrated that small differences in the structure (8-azaguanine versus 8-aza-9-deazaguanine) might lead to significant differences in recognition efficiency and selectivity, base pairing by Hoogsteen recognition at the polymerase level is possible, 8-aza-9-deazaguanine represents a self-complementary base pair, and a correlation exists between in vitro incorporation studies and in vivo recognition by natural bases in Escherichia coli, but this recognition is not absolute (exceptions were observed).
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DNA Polimerase Dirigida por DNA/metabolismo , DNA/metabolismo , Nucleotídeos de Purina/metabolismo , 5-Metilcitosina , Azaguanina , Pareamento de Bases , Escherichia coli/enzimologia , Escherichia coli/genética , HipoxantinaRESUMO
We evaluated the spatial-temporal dispersion of airborne nanomaterials during the use of spray consumer products and estimated the level of consumer inhalation exposure. A total of eight spray products including five propellant and three pump types were selected to evaluate the dispersion of airborne nanoparticles across time and space in a cleanroom which could control the background particles. Four products were advertised to contain silver and one contained titanium nanoparticles, while three products were specified no ENM but as being manufactured through the use of nanotechnology. We used direct-reading instruments with a thermodesorber unit to measure the particles (number, mass, surface area), as well as filter sampling to examine physicochemical characteristics. Sampling was conducted simultaneously at each location (1 m, near-field; 2, 3 m, far-field) by distance from the source. We estimated the inhaled doses at the breathing zone, and the doses deposited in each part of the respiratory tract using the experimental data and mathematical models. Nanoparticles released from the propellant sprays persisted in the air and dispersed over a large distance due to their small size (1466-5565 particles/cm3). Conversely, the pump sprays produced larger droplets that settled out of the air relatively close to the source, so the concentration was similar to background level (<200 particles/cm3). The estimates of inhalation exposure also suggested that exposure to nanoparticles was greater with propellant sprays (1.2 × 108 ± 4.0 × 107 particles/kgbw/day) than pump sprays (2.7 × 107 ± 6.5 × 106 particles/kgbw/day). We concluded that the propellant sprays create a higher risk of exposure than the pump sprays.
Assuntos
Exposição por Inalação , Nanopartículas , Aerossóis , Cosméticos , Produtos Domésticos , Humanos , Nanotecnologia , Tamanho da Partícula , PrataRESUMO
Spotted wing drosophila (SWD, Drosophila suzukii (Matsumura), Diptera: Drosophilidae) is recognized as an economically important pest in North America and Europe as well as in Asia. Assessments were made for fumigant and contact toxicities of six Myrtaceae plant essential oils (EOs) and their components to find new alternative types of insecticides active against SWD. Among the EOs tested, Leptospermum citratum EO, consisting mainly of geranial and neral, exhibited effective fumigant activity. Median lethal dose (LD50; mg/L) values of L. citratum were 2.39 and 3.24 for males and females, respectively. All tested EOs except Kunzea ambigua EO exhibited effective contact toxicity. LD50 (µg/fly) values for contact toxicity of manuka and kanuka were 0.60 and 0.71, respectively, for males and 1.10 and 1.23, respectively, for females. The LD50 values of the other 3 EOs-L. citratum, allspice and clove bud were 2.11-3.31 and 3.53-5.22 for males and females, respectively. The non-polar fraction of manuka and kanuka did not show significant contact toxicity, whereas the polar and triketone fractions, composed of flavesone, isoleptospermone and leptospermone, exhibited efficient activity with the LD50 values of 0.13-0.37 and 0.22-0.57 µg/fly for males and females, respectively. Our results indicate that Myrtaceae plant EOs and their triketone components can be used as alternatives to conventional insecticides.
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Drosophila/efeitos dos fármacos , Inseticidas/farmacologia , Cetonas/farmacologia , Myrtaceae/química , Óleos Voláteis/farmacologia , Animais , Feminino , Inseticidas/química , Cetonas/química , Kunzea/química , Leptospermum/química , Dose Letal Mediana , Masculino , Estrutura Molecular , Óleos Voláteis/química , Óleos de Plantas/química , Óleos de Plantas/farmacologiaRESUMO
Fumigant and contact toxicities of 22 plant essential oils (EOs) from 14 families and their constituents against the adult spotted wing drosophila (SWD), Drosophila suzukii were examined. Analyses by GC, GC-MS, and NMR led to the identification of 2, 16, 13, 4, 6, 9, and 10 compounds from Gaultheria fragrantissima, Croton anistatum, Illicium verum, Liquidamabar orientalis, Cinnamomum cassia, Rosa damasena, and Santalum album, respectively. In fumigant toxicity test, G. fragrantissima, C. anistatum, and I. verum exhibited 100, 93.8, and 95.8, and 100, 70.0, and 80.0% mortalities against the adult male and female SWD at 4.41mg/L air, respectively. LC50 values (mg/L air) of G. fragrantissima, C. anistatum, and I. verum were 3.46, 3.67, and 3.16 against male, and 3.48, 4.31, and 4.01 against female SWD. LC50 values (mg/L air) of methyl salicylate and trans-anethole were 2.17 and 1.75 against male and 2.65 and 3.00 against female SWD, respectively. In contact toxicity tests, L. orientalis, C. cassia, R. damasena, and S. album showed insecticidal activity with LD50 values (µg/fly) of 2.64, 1.84, 3.40 and 2.18 against male SWD and of 3.74, 2.24, 8.91 and 5.61 against female SWD, respectively. 2-Phehy-1-ethanol, 3-phenyl-1-propanol, trans-cinnamaldehyde, trans-cinnamyl alcohol, and α-santalol also exhibited insecticidal activity with LD50 values of 9.79, 5.52, 2.39, 3.02 and 2.37 against male SWD and of 11.77, 7.04, 2.94, 3.32, and 3.99 against female SWD, respectively. trans-Cinnamaldehyde exhibited the highest AChE inhibition but its inhibition is likely due to a non-specific chemical inhibition. Our results indicate that wooden EOs and their components can be used as fumigants or spray-type control agents against SWD.
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Drosophila/efeitos dos fármacos , Inseticidas/toxicidade , Óleos Voláteis/toxicidade , Óleos de Plantas/toxicidade , Acetilcolinesterase/metabolismo , Animais , Inibidores da Colinesterase/análise , Inibidores da Colinesterase/toxicidade , Drosophila/metabolismo , Feminino , Fumigação , Proteínas de Insetos/antagonistas & inibidores , Proteínas de Insetos/metabolismo , Inseticidas/análise , Dose Letal Mediana , Magnoliopsida/química , Masculino , Óleos Voláteis/análise , Extratos Vegetais/química , Óleos de Plantas/análise , Madeira/químicaRESUMO
Background: Formaldehyde was classified as a Group I Carcinogen by the International Agency for Research on Cancer (IARC) in 2006. While the IARC has stated that there is a lack of evidence that formaldehyde causes brain cancer, three meta-analyses have consistently reported a significantly higher risk of brain cancer in workers exposed to high levels of formaldehyde. Therefore, we report a case of a worker who was diagnosed with glioblastoma after being exposed to high concentrations of formaldehyde while working with formaldehyde resin in the paper industry. Case presentation: A 40-year-old male patient joined an impregnated paper manufacturer and performed impregnation work using formaldehyde resin for 10 years and 2 months. In 2017, the patient experienced a severe headache and visited the hospital for brain magnetic resonance imaging, which revealed a mass. In the same year, the patient underwent a craniotomy for brain tumor resection and was diagnosed with glioblastoma of the temporal lobe. In 2019, a craniotomy was performed owing to the recurrence of the brain tumor, but he died in 2020. An exposure assessment of the work environment determined that the patient was exposed to formaldehyde above the exposure threshold of 0.3 ppm continuously for more than 10 years and that he had high respiratory and dermal exposure through performing work without wearing a respirator or protective gloves. Conclusions: This case report represents the first instance where the epidemiological investigation and evaluation committee of the Occupational Safety and Health Research Institute in Korea recognized the scientific evidence of work-related brain tumors due to long-term exposure to high concentrations of formaldehyde during impregnated paperwork. This case highlights the importance of proper workplace management, informing workers that prolonged exposure to formaldehyde in impregnation work can cause brain tumors and minimizing exposure in similar processes.
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TAM receptor tyrosine kinases have emerged as promising therapeutic targets for cancer treatment due to their roles in both tumor intrinsic survival mechanisms and suppression of antitumor immunity within the tumor microenvironment. Inhibiting MerTK and Axl selectively is believed to hinder cancer cell survival, reverse the protumor myeloid phenotype, and suppress efferocytosis, thereby eliciting an antitumor immune response. In this study, we present the discovery of A-910, a highly potent and selective dual MerTK/Axl inhibitor, achieved through a structure-based medicinal chemistry campaign. The lead compound exhibits favorable oral bioavailability, exceptional kinome selectivity, and significantly improved in vivo target engagement. These findings support the use of A-910 as an orally bioavailable in vivo tool compound for investigating the immunotherapy potential of dual MerTK/Axl inhibition.
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A new synthesis route to α-L-threose nucleoside phosphonates via 2-O and 3-O selectively protected L-threose is developed. The key intermediates 2-O-benzoyl-L-threonolactone and 1-O-acetyl-2-O-benzoyl-3-O-t-butyldiphenylsilyl-L-threofuranose were functionalized to synthesize 2'-deoxy-2'-fluoro- and 3'-C-ethynyl L-threose 3'-O-phosphonate nucleosides. The key intermediates developed are important intermediates for the synthesis of new L-threose-based nucleoside analogues, TNA phosphoramidites, and TNA triphosphates.
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Carboidratos/química , Nucleosídeos/síntese química , Organofosfonatos/síntese química , Tetroses/síntese química , Conformação Molecular , Nucleosídeos/química , Organofosfonatos/química , Estereoisomerismo , Tetroses/químicaRESUMO
An efficient synthesis of a library of 5-amino-thiazolo[4,5-d]pyrimidines is reported. Regioselective displacements of chlorines, as well as regioselective diazotation reactions are described, which allow the introduction of structural diversity on the scaffold by consecutive reactions. Screening of this focused library led to the discovery of SecA inhibitors from Escherichia coli and Staphylococcus aureus.
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Adenosina Trifosfatases/antagonistas & inibidores , Proteínas de Bactérias/antagonistas & inibidores , Escherichia coli/enzimologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Staphylococcus aureus/enzimologia , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Proteínas de Membrana Transportadoras , Canais de Translocação SEC , Proteínas SecARESUMO
The synthesis of a new series of 4-N-piperazinyl-thieno[2,3-d]pyrimidines is described. The synthetic route allows introducing structural variety at positions 2, 4 and 6 of the scaffold. Evaluation of their immunosuppressive activity in a Mixed Lymphocyte Reaction (MLR) assay revealed that the most potent compound has an IC(50)-value of 66 nM and therefore deserves attention for further medicinal chemistry optimization.
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Imunossupressores/síntese química , Imunossupressores/farmacologia , Piperazinas/síntese química , Piperazinas/farmacologia , Pirimidinas/síntese química , Pirimidinas/farmacologia , Relação Dose-Resposta Imunológica , Humanos , Teste de Cultura Mista de Linfócitos/métodos , Linfócitos/efeitos dos fármacos , Linfócitos/imunologia , Relação Estrutura-AtividadeRESUMO
Enclosed underground excavation worksite has an environment with poor ventilation and exposure to hazardous substances from diesel engine exhaust and construction materials. The objective of this study was to evaluate the exposure level of elemental carbon (EC), organic carbon (OC), total carbon (TC), polycyclic aromatic hydrocarbons (PAHs), dust and crystalline silica (CS) during underground excavation work for top down construction buildings. Active local air sampling for EC, OC, and TC (n = 105), PAHs (n = 50), dust (n = 34) and CS (n = 34) was conducted from inside and outside the excavator at underground excavation workshop in four different construction sites. EC, OC, TC and CS were sampled with each respirable and total particulates. EC, OC, and TC were collected on quartz-filter and analyzed using the thermal optical transmittance method. PAHs was collected on polytetrafluorethylene filter with XAD-2 and analyzed using liquid chromatography with fluorescence detector. CS and particulates were collected on poly vinyl chloride filter and analyzed using fourier-transform infrared spectroscopy. The geometric mean of respirable EC, OC, TC, total PAHs, respirable dust and respirable CS were 8.69 µg/m3, 34.32 µg/m3, 44.96 µg/m3, 6.818 µg/m3 0.13 mg/m3 and 0.02 mg/m3 from inside the excavator and 33.20 µg/m3, 46.53 µg/m3, 78.21 µg/m3, 3.934 µg/m3, 0.9 mg/m3 and 0.08 mg/m3 from outside the excavator (underground excavation workshop), respectively. The EC and RCS concentration from outside the excavator is significantly higher than that of inside the excavator (p<0.01). The worksite with rock ground, higher vehicle density, blasting and enclosed environments had higher exposure to EC than other sites (p<0.05). There was no significant difference of EC concentration between total and respirable particulates. In top down construction sites, EC concentrations during underground excavation work exceeded recommended exposure limits as 20 µg/m3, accounted for about 50% of the total sample, and the level of concentration of RCS exceeded 1.5 times of occupational exposure limit, 0.05 mg/m3. Efforts are needed to minimize exposure to diesel engine exhaust and silica in underground excavation sites. Management of diesel engine vehicle, supply of fresh air and ventilation and introducing water facilities to create wet environment in underground worksites are strongly suggested.
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Poluentes Ocupacionais do Ar/análise , Exposição Ambiental/efeitos adversos , Monitoramento Ambiental/métodos , Carbono/análise , Poeira/análise , Exposição Ambiental/análise , Humanos , Exposição por Inalação/análise , Exposição Ocupacional/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , República da Coreia , Dióxido de Silício/análise , Emissões de Veículos/análise , Local de TrabalhoRESUMO
BACKGROUND: The photolithography process in the semiconductor industry uses various chemicals with little information on their constitution. This study aimed to identify the chemical constituents of photoresist (PR) products and their by-products and to compare these constituents with material safety data sheets (MSDSs) and analytical results. METHODS: A total of 51 PRs with 48 MSDSs were collected. Analysis consisted of two parts: First, the constituents of the chemical products were identified and analyzed using MSDS data; second, for verification of the by-products of PR, volatile organic compounds were analyzed. The chemical constituents were categorized according to hazards. RESULTS: Forty-five of 48 products contained trade secrets in amounts ranging from 1 to 65%. A total of 238 ingredients with multiple counting (35 ingredients without multiple counting) were identified in the MSDS data, and 48.7% of ingredients were labeled as trade secrets under the Korea Occupational Safety and Health Act. The concordance rate between the MSDS data and the analytical result was 41.7%. The by-product analysis identified 129 chemicals classified according to Chemical Abstracts Service No., with 17 chemicals that are carcinogenic, mutagenic, and reprotoxic substances. Formaldehyde was found to be released from 12 of 21 products that use novolak resin. CONCLUSION: We confirmed that several PRs contain carcinogens, and some were not specified in the toxicological information in the MSDS. Hazardous chemicals, including benzene and formaldehyde, are released from PRs products as by-products. Therefore, it is necessary to establish a systematic management system for chemical compounds and the working environment.
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The primary target of a novel series of immunosuppressive 7-piperazin-1-ylthiazolo[5,4- d]pyrimidin-5-amines was identified as the lipid kinase, PI4KIIIß. Evaluation of the series highlighted their poor solubility and unwanted off-target activities. A medicinal chemistry strategy was put in place to optimize physicochemical properties within the series, while maintaining potency and improving selectivity over other lipid kinases. Compound 22 was initially identified and profiled in vivo, before further modifications led to the discovery of 44 (UCB9608), a vastly more soluble, selective compound with improved metabolic stability and excellent pharmacokinetic profile. A co-crystal structure of 44 with PI4KIIIß was solved, confirming the binding mode of this class of inhibitor. The much-improved in vivo profile of 44 positions it as an ideal tool compound to further establish the link between PI4KIIIß inhibition and prolonged allogeneic organ engraftment, and suppression of immune responses in vivo.
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Inibidores Enzimáticos/farmacologia , Inibidores Enzimáticos/farmacocinética , Fosfotransferases (Aceptor do Grupo Álcool)/antagonistas & inibidores , Piperazinas/farmacologia , Piperazinas/farmacocinética , Piperidinas/farmacologia , Transplante Homólogo , Administração Oral , Animais , Disponibilidade Biológica , Inibidores Enzimáticos/administração & dosagem , Inibidores Enzimáticos/metabolismo , Humanos , Imunossupressores/administração & dosagem , Imunossupressores/metabolismo , Imunossupressores/farmacocinética , Imunossupressores/farmacologia , Camundongos , Simulação de Acoplamento Molecular , Fosfotransferases (Aceptor do Grupo Álcool)/química , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Piperazinas/administração & dosagem , Piperazinas/metabolismo , Piperidinas/administração & dosagem , Piperidinas/metabolismo , Conformação ProteicaRESUMO
BACKGROUND: The spotted-wing drosophila (SWD), Drosophila suzukii (Matsumura), is a globally invasive and serious pest of numerous soft-skinned fruit crops. Assessments were made of fumigant and contact toxicities of 12 Myrtaceae plant essential oils (EOs) and their components. For determining the mode of action of major components of active EOs, their activities against acetylcholinesterase (AChE) and Glutathione S-transferase (GST) were also assessed. RESULTS: Strong fumigant and contact toxicities were observed from EOs of Eucalyptus citriodora and Melaleuca teretifolia. The main components of E. citriodora were citronellal and isopulegol, whereas those of M. teretifolia were neral and geranial. Geranial showed the strongest fumigant activity, followed by citronellal or neral, M. teretifolia EO, isopulegol and E. citriodora EO. In contact toxicity assays, geranial also exhibited the strongest insecticidal activity, followed by neral or M. teretifolia EO, citronellol, citronellal, isopulegol and E. citriodora EO. Among the major components, all compounds showed low AChE inhibitory activity, while neral and geranial showed GST inhibitory activity against SWD. CONCLUSION: Myrtaceae plant EOs and their components have an excellent potential for being used in the control of SWD adults and could be useful in the development of more effective natural compounds as alternatives to synthetic pesticides. © 2016 Society of Chemical Industry.
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Drosophila , Inseticidas , Myrtaceae/química , Óleos Voláteis , Acetilcolinesterase/metabolismo , Animais , Inibidores da Colinesterase/farmacologia , Drosophila/enzimologia , Glutationa Transferase/antagonistas & inibidores , Óleos Voláteis/farmacologiaRESUMO
Drosophila suzukii is an economically important pest in America and Europe as well as in Asia. Sparassol and methyl orsellinate are naturally produced by the cultivating mushrooms Sparassis cripta and Sparassis latifolia. Fumigant and contact toxicities of synthetic sparassol and its analogues, methyl orsellinate and methyl 2,4-dimethoxy-6-methylbenzoate (DMB), were investigated. Negligible fumigant activity was observed from the tested compounds. However, DMB showed the strongest contact toxicity, followed by sparassol and methyl orsellinate. The possible modes of action of the compounds were assessed for their acetylcholinesterase (AChE)- and glutathione S-transferase (GST)-inhibiting activities. AChE activity was weakly inhibited by methyl orsellinate and DMB, but GST was inhibited by sparassol, methyl orsellinate, and DMB. Thus, DMB could be a promising alternative to common insecticides as it can be easily synthesized from sparassol, which is the natural product of Sparassis species. Sparassis species could be an industrial resource of DMB.
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Agaricales/química , Drosophila/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Glutationa Transferase/antagonistas & inibidores , Inseticidas/farmacologia , Resorcinóis/farmacologia , Acetilcolinesterase/metabolismo , Animais , Drosophila/enzimologia , Proteínas de Drosophila/antagonistas & inibidores , Proteínas de Drosophila/metabolismo , Inibidores Enzimáticos/química , Glutationa Transferase/metabolismo , Controle de Insetos , Inseticidas/química , Resorcinóis/química , Estações do AnoRESUMO
Herein we report the synthesis of N8-glycosylated 8-aza-deoxyguanosine (N8-8-aza-dG) and 8-aza-9-deaza-deoxyguanosine (N8-8-aza-9-deaza-dG) nucleotides and their base pairing properties with 5-methyl-isocytosine (d-isoCMe), 8-amino-deoxyinosine (8-NH2-dI), 1-N-methyl-8-amino-deoxyinosine (1-Me-8-NH2-dI), 7,8-dihydro-8-oxo-deoxyinosine (8-Oxo-dI), 7,8-dihydro-8-oxo-deoxyadenosine (8-Oxo-dA), and 7,8-dihydro-8-oxo-deoxyguanosine (8-Oxo-dG), in comparison with the d-isoCMe:d-isoG artificial genetic system. As demonstrated by Tm measurements, the N8-8-aza-dG:d-isoCMe base pair formed less stable duplexes as the C:G and d-isoCMe:d-isoG pairs. Incorporation of 8-NH2-dI versus the N8-8-aza-dG nucleoside resulted in a greater reduction in Tm stability, compared to d-isoCMe:d-isoG. Insertion of the methyl group at the N1 position of 8-NH2-dI did not affect duplex stability with N8-8-aza-dG, thus suggesting that the base paring takes place through Hoogsteen base pairing. The cellular interpretation of the nucleosides was studied, whereby a lack of recognition or mispairing of the incorporated nucleotides with the canonical DNA bases indicated the extent of orthogonality in vivo. The most biologically orthogonal nucleosides identified included the 8-amino-deoxyinosines (1-Me-8-NH2-dI and 8-NH2-dI) and N8-8-aza-9-deaza-dG. The 8-oxo modifications mimic oxidative damage ahead of cancer development, and the impact of the MutM mediated recognition of these 8-oxo-deoxynucleosides was studied, finding no significant impact in their in vivo assay.
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[This corrects the article DOI: 10.1039/C5SC03474D.].
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PURPOSE: Gamma radiation on Helicoverpa armigera Hübner was performed to assess developmental inhibition and to identify a potential quarantine treatment dose of the radiation. MATERIALS AND METHODS: Gamma radiation ((60)Co) treatment at different doses of 50, 100, 200, 300, and 400 Gy was carried out with egg, larvae, pupae and adults of H. armigera. RESULTS: Gamma radiation induced developmental inhibition of all stages of H. armigera. The effective dose values required for inhibition 99% (ED(99)) of hatching, pupation and adult emergence from the irradiated eggs were 550.7, 324.9 and 136.4 Gy, respectively. ED(99) values for inhibition of the larvae to adult emergence was 200.0 Gy. Irradiation on pupae could not completely inhibit adult emergence even at 400 Gy. ED(99) value for inhibition of F(1) egg hatchability from the irradiated adults was estimated to be 229.5 Gy. CONCLUSIONS: This study suggests that gamma radiation is a possible alternative to phytosanitary treatments. Irradiation treatment with minimum dose of 200 Gy can be suggested as optimum dose for larval treatment in quarantine.
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Dano ao DNA , Raios gama , Mariposas/crescimento & desenvolvimento , Mariposas/efeitos da radiação , Animais , Cruzamento , Ensaio Cometa , Feminino , Larva/crescimento & desenvolvimento , Larva/efeitos da radiação , Masculino , Mariposas/genética , Controle de Pragas , Pupa/crescimento & desenvolvimento , Pupa/efeitos da radiaçãoRESUMO
The selection of artificial nucleic acids to be used for synthetic biology purposes is based on their structural and biochemical orthogonality to the natural system. We describe the example of a nucleotide mimic that functions as a substrate for polymerases and in which the carbohydrate moiety as well as the base moiety and the leaving group are different from that of the natural building blocks. The nucleotides themselves have two anomeric centers, and different leaving group properties of substituents at both anomeric centers need to be exploited to perform selective glycosylation reactions for their synthesis. In addition, the reversibility of the polymerase reaction at the level of the template has been demonstrated when pyrophosphate functions as leaving group and not with the alternative leaving groups.