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121.
122.
Elisa Pileggi Michaela Serpi Graciela Andrei Dominique Schols Robert Snoeck Fabrizio Pertusati 《Bioorganic & medicinal chemistry》2018,26(12):3596-3609
The importance of phosphonoamidate prodrugs (ProTides) of acyclic nucleoside phosphonate (ANPs) is highlighted by the approval of Tenofovir Alafenamide Fumarate for the treatment of HIV and HBV infections. In the present paper we are reporting an expedient, one-pot, two-steps synthesis of allyl phosphonoamidates and diamidates that offers a time saving strategy when compared to literature methods. The use of these substrates in the cross metathesis reactions with alkenyl functionalised thymine and uracil nucleobases is reported. ANPs prodrugs synthesized via this methodology were evaluated for their antiviral activities against DNA and RNA viruses. It is anticipated that the use of 5,6,7,8-tetrahydro-1-napthyl as aryloxy moiety is capable to confer antiviral activity among a series of otherwise inactive uracil ProTides. 相似文献
123.
Carolina Virginia Temperini Alejandro Guillermo Pardo Graciela Noemí Pose 《Aerobiologia》2018,34(2):227-239
Fungal spores are normal components of external environments. They have been reported to be associated with human, animal and plant diseases causing primary and opportunistic infections. Cladosporium is commonly the most frequently isolated genus from air samples, and its species are considered mainly saprophytic, but there is a wide variety of taxa that can cause adverse effects on human and animal health and also on plants. In this work, we aimed to record Cladosporium spores frequency of isolation in northern Argentinean Patagonia and to perform a molecular characterization based on actin gene complemented with EF1α and ITS genes. The ability of the pathogens to cause disease in pip fruits of Packham’s Triumph and Abate Fetel pears and red delicious apples was determined. Results confirmed Cladosporium spores as the main genera isolated from air samples, and the molecular characterization revealed the existence of 11 species in this region grouped in C. cladosporioides and C. herbarum complexes. Pathogenicity tests revealed that Cladosporium sp. cause disease on fruit. Abate Fetel was the most susceptible to infection. These results compose the first study in Argentina in respect of identification at species level of airborne Cladosporium spores, and furthermore, it is the first report in northern Patagonia and the high valley of Río Negro productive region. This knowledge can help farmers to take preventive measures in order to avoid biological damage. 相似文献
124.
Nancy L. Charó Natalia M. Galigniana Graciela Piwien-Pilipuk 《Biochimica et Biophysica Acta (BBA)/Molecular Cell Research》2018,1865(2):432-443
Confocal and electron microscopy images, and WB analysis of cellular fractions revealed that HP1γ is in the nucleus but also in the cytoplasm of C2C12 myoblasts, myotubes, skeletal and cardiac muscles, N2a, HeLa and HEK293T cells. Signal specificity was tested with different antibodies and by HP1γ knockdown. Leptomycin B treatment of myoblasts increased nuclear HP1γ, suggesting that its nuclear export is Crm-1-dependent. HP1γ exhibited a filamentous pattern of staining partially co-localizing with actin in the cytoplasm of myotubes and myofibrils. Immunoelectron microscopic analysis showed high-density immunogold particles that correspond to HP1γ localized to the Z-disk and A-band of the sarcomere of skeletal muscle. HP1γ partially co-localized with actin in C2C12 myotubes and murine myofibrils. Importantly, actin co-immunoprecipitated with HP1γ in the nuclear and cytosolic fractions of myoblasts. Actin co-immunoprecipitated with HP1γ in myoblasts incubated in the absence or presence of the actin depolymerizing agent cytochalasin D, suggesting that HP1γ may interact with G-and F-actin. In the cytoplasm, HP1γ was associated to the perinuclear actin cap that controls nuclear shape and position. In the nucleus, re-ChIP assays showed that HP1γ-actin associates to the promoter and transcribed regions of the house keeping gene GAPDH, suggesting that HP1γ may function as a scaffold protein for the recruitment of actin to control gene expression. When HP1γ was knocked-down, myoblasts were unable to differentiate or originated thin myotubes. In summary, HP1γ is present in the nucleus and the cytoplasm interacting with actin, a protein complex that may exert different functions depending on its subcellular localization. 相似文献
125.
Vanesa Amarelle Federico Rosconi Juan Manuel Lázaro-Martínez Graciela Buldain Francisco Noya Mark R. O’Brian Elena Fabiano 《Biometals》2016,29(2):333-347
Ensifer meliloti is a nitrogen-fixing symbiont of the alfalfa legume able to use heme as an iron source. The transport mechanism involved in heme acquisition in E. meliloti has been identified and characterized, but the fate of heme once inside the cell is not known. In silico analysis of E. meliloti 1021 genome revealed no canonical heme oxygenases although two genes encoding putative heme degrading enzymes, smc01518 and hmuS, were identified. SMc01518 is similar to HmuQ of Bradyrhizobium japonicum, which is weakly homologous to the Staphylococcus aureus IsdG heme-degrading monooxygenase, whereas HmuS is homolog to Pseudomonas aeruginosa PhuS, a protein reported as a heme chaperone and as a heme degrading enzyme. Recombinant HmuQ and HmuS were able to bind hemin with a 1:1 stoichiometry and displayed a Kd value of 5 and 4 µM, respectively. HmuS degrades heme in vitro to the biliverdin isomers IX-β and IX-δ in an equimolar ratio. The HmuQ recombinant protein degrades heme to biliverdin IX-δ only. Additionally, in this work we demonstrate that humS and hmuQ gene expression is regulated by iron and heme in a RirA dependent manner and that both proteins are involved in heme metabolism in E. meliloti in vivo. 相似文献
126.
127.
Hydrolysis of Pork Muscle Sarcoplasmic Proteins by Lactobacillus curvatus and Lactobacillus sake 总被引:4,自引:0,他引:4 下载免费PDF全文
Silvina Fadda Yolanda Sanz Graciela Vignolo M.-Concepcin Aristoy Guillermo Oliver Fidel Toldr 《Applied microbiology》1999,65(2):578-584
Lactobacillus curvatus CECT 904 and Lactobacillus sake CECT 4808 were selected on the basis of their proteolytic activities against synthetic substrates. Further, the effects of whole cells, cell extracts, and a combination of both enzymatic sources on muscle sarcoplasmic proteins were determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and reverse-phase high-performance liquid chromatography analyses. Strains of both species displayed proteinase activities on five sarcoplasmic proteins. The inoculation of whole cells caused a degradation of peptides, whereas the addition of cell extracts resulted in the generation of both hydrophilic and hydrophobic peptides. This phenomenon was remarkably more pronounced when L. curvatus was involved. Whole cells also consumed a great amount of free amino acids, while the addition of intracellular enzymes contributed to their generation. L. sake accounted for a greater release of free amino acids. In general, cell viability and also proteolytic events were promoted when cell suspensions were provided with cell extracts as an extra source of enzymes. 相似文献
128.
Jo Ishizawa Kensuke Kojima Teresa McQueen Vivian Ruvolo Dhruv Chachad Graciela M. Nogueras-Gonzalez Xuelin Huang William E. Pierceall E. J. Dettman Michael H. Cardone Sharon Shacham Marina Konopleva Michael Andreeff 《PloS one》2015,10(9)
BH3 profiling measures the propensity of transformed cells to undergo intrinsic apoptosis and is determined by exposing cells to BH3-mimicking peptides. We hypothesized that basal levels of prosurvival BCL-2 family proteins may modulate the predictive power of BH3 profiling and termed it mitochondrial profiling. We investigated the correlation between cell sensitivity to apoptogenic agents and mitochondrial profiling, using a panel of acute myeloid leukemias induced to undergo apoptosis by exposure to cytarabine, the BH3 mimetic ABT-199, the MDM2 inhibitor Nutlin-3a, or the CRM1 inhibitor KPT-330. We found that the apoptogenic efficacies of ABT-199 and cytarabine correlated well with BH3 profiling reflecting BCL2, but not BCL-XL or MCL-1 dependence. Baseline BCL-2 protein expression analysis increased the ability of BH3 profiling to predict resistance mediated by MCL-1. By utilizing engineered cells with overexpression or knockdown of BCL-2 family proteins, Ara-C was found to be independent, while ABT-199 was dependent on BCL-XL. BCL-2 and BCL-XL overexpression mediated resistance to KPT-330 which was not reflected in the BH3 profiling assay, or in baseline BCL-2 protein levels. In conclusion, mitochondrial profiling, the combination of BH3 profiling and prosurvival BCL-2 family protein analysis, represents an improved approach to predict efficacy of diverse agents in AML and may have utility in the design of more effective drug combinations. 相似文献
129.
This study contributes to the investigation related to guest–host interactions between the chemotherapeutic agent cisplatin and a functionalised silica matrix in order to improve and find new materials such as drug carriers. The adsorption of cisplatin and its complexes, cis-[PtCl(NH3)2]+ and cis-[Pt(NH3)2]2+, on a SH-functionalised SiO2(111) surface has been studied by the atom superposition and electron delocalisation method. The adiabatic energy curves for the adsorption of the drug and its products on the delivery system were considered. The electronic structure and bonding analysis were also performed. The molecule and their complex are adsorbed on the functionalised surface resulting in a major absorption of the cis-[Pt(NH3)2]2+ complex. The molecule–surface interactions are formed via –SH group. The molecule/complexes SH electron-donating effect plays an important role in the catalytic reaction. The more important drug–carrier interactions occur through the Cl–H bond for the adsorption of cis-[PtCl2(NH3)2] and cis-[PtCl(NH3)2]+, and through the Pt–S and Pt–H interactions for cis-[Pt(NH3)2]2+ adsorption. When the new interactions are formed, the functionalised carrier maintains their matrix properties while the molecule is the most affected after adsorption. The Pt atomic orbitals present the most important changes during adsorption. 相似文献
130.