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231.
Jovana J. Ajduković Evgenija A. Djurendić Edward T. Petri Olivera R. Klisurić Andjelka S. Ćelić Marija N. Sakač Dimitar S. Jakimov Katarina M. Penov Gaši 《Bioorganic & medicinal chemistry》2013,21(23):7257-7266
We report a rapid and efficient synthesis of A-ring modified 17α-picolyl and 17(E)-picolinylidene androstane derivatives from dehydroepiandrosterone. Compounds were validated spectroscopically and structurally characterized by X-ray crystallography. Virtual screening by molecular docking against clinical targets of steroidal anticancer drugs (ERα, AR, Aromatase and CYP17A1) suggests that 17(E)-picolinylidene, but not 17α-picolyl androstanes could specifically interact with CYP17A1 (17α-hydroxylase) with similar geometry and affinity as Abiraterone, a 17-pyridinyl androstane drug clinically used in the treatment of prostate cancer. In addition, several 17(E)-picolinylidene androstanes demonstrated selective antiproliferative activity against PC3 prostate cancer cells, which correlates with Abiraterone antiproliferative activity and predicted CYP17A1 binding affinities. Based on these preliminary results, 17(E)-picolinylidene androstane derivatives could be a promising starting point for the development of new compounds for the treatment of prostate cancer. 相似文献
232.
Stanojlović O Rasić-Marković A Hrncić D Susić V Macut D Radosavljević T Djuric D 《Cellular and molecular neurobiology》2009,29(3):329-339
d,l-Homocysteine thiolactone (H), a reactive homocysteine metabolite, contributes to total homocysteine pool. The aim of the
present study was to determine the effects of H after acute application in increasing doses to rats. Adult Wistar rat were
intraperitoneally administered saline or H in increasing doses (5.5, 8.0, or 11.0 mmol/kg). For electroencephalographic (EEG)
recordings, three gold-plated screws were implanted into the skull and animals were supervised. We observed H-induced two
types of seizures, the coexistence of convulsive and nonconvulsive epilepsy. Dose-related increase in the number and severity
(0–4) of displaying convulsions was recorded. In H5.5 group, the majority of seizure episodes were grade 1 (62.5 and 0% lethality), in H8 40% grade 2, and in H11 grade 4 in 42.11% (100% lethal outcome). EEGs recordings in convulsive animals showed a high-voltage spike-wave and polyspikes
complexes. The second, absence-like, nonconvulsive seizures were accompanied by the EEGs mostly with 6–8 Hz spikes-and-wave
discharges (SWD). Latency time to the generalized clonic-tonic seizures overlapped with the time of the maximal median number
and median duration of the SWD per 15 min during 90-min observing period. The results show that acute H administration significantly
changes neurons, EEG tracings, and behavioral responses and suggests a possible model for studying petit mal epilepsy. 相似文献
233.
Bonet-Costa C Vilaseca M Diema C Vujatovic O Vaquero A Omeñaca N Castejón L Bernués J Giralt E Azorín F 《Journal of Proteomics》2012,75(13):4124-4138
Linker histone H1 is a major chromatin component that binds internucleosomal DNA and mediates the folding of nucleosomes into a higher-order structure, namely the 30-nm chromatin fiber. Multiple post-translational modifications (PTMs) of core histones H2A, H2B, H3 and H4 have been identified and their important contribution to the regulation of chromatin structure and function is firmly established. In contrast, little is known about histone H1 modifications and their function. Here we address this question in Drosophila melanogaster, which, in contrast to most eukaryotic species, contains a single histone H1 variant, dH1. For this purpose, we combined bottom-up and top-down mass-spectrometry strategies. Our results indicated that dH1 is extensively modified by phosphorylation, methylation, acetylation and ubiquitination, with most PTMs falling in the N-terminal domain. Interestingly, several dH1 N-terminal modifications have also been reported in specific human and/or mouse H1 variants, suggesting that they have conserved functions. In this regard, we also provide evidence for the contribution of one of such conserved PTMs, dimethylation of K27, to heterochromatin organization during mitosis. Furthermore, our results also identified multiple dH1 isoforms carrying several phosphorylations and/or methylations, illustrating the high structural heterogeneity of dH1. In particular, we identified several non-CDK sites at the N-terminal domain that appear to be hierarchically phosphorylated. This study provides the most comprehensive PTM characterization of any histone H1 variant to date. 相似文献
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236.
Signal recognition particle-dependent inner membrane targeting of the PulG Pseudopilin component of a type II secretion system 下载免费PDF全文
Francetic O Buddelmeijer N Lewenza S Kumamoto CA Pugsley AP 《Journal of bacteriology》2007,189(5):1783-1793
The pseudopilin PulG is an essential component of the pullulanase-specific type II secretion system from Klebsiella oxytoca. PulG is the major subunit of a short, thin-filament pseudopilus, which presumably elongates and retracts in the periplasm, acting as a dynamic piston to promote pullulanase secretion. It has a signal sequence-like N-terminal segment that, according to studies with green and red fluorescent protein chimeras, anchors unassembled PulG in the inner membrane. We analyzed the early steps of PulG inner membrane targeting and insertion in Escherichia coli derivatives defective in different protein targeting and export factors. The beta-galactosidase activity in strains producing a PulG-LacZ hybrid protein increased substantially when the dsbA, dsbB, or all sec genes tested except secB were compromised by mutations. To facilitate analysis of native PulG membrane insertion, a leader peptidase cleavage site was engineered downstream from the N-terminal transmembrane segment (PrePulG*). Unprocessed PrePulG* was detected in strains carrying mutations in secA, secY, secE, and secD genes, including some novel alleles of secY and secD. Furthermore, depletion of the Ffh component of the signal recognition particle (SRP) completely abolished PrePulG* processing, without affecting the Sec-dependent export of periplasmic MalE and RbsB proteins. Thus, PulG is cotranslationally targeted to the inner membrane Sec translocase by SRP. 相似文献
237.
238.
R. E. Cardoza S. P. McCormick M. G. Malmierca E. R. Olivera N. J. Alexander E. Monte S. Gutiérrez 《Applied and environmental microbiology》2015,81(18):6355-6366
Trichothecenes are fungal sesquiterpenoid compounds, the majority of which have phytotoxic activity. They contaminate food and feed stocks, resulting in potential harm to animals and human beings. Trichoderma brevicompactum and T. arundinaceum produce trichodermin and harzianum A (HA), respectively, two trichothecenes that show different bioactive properties. Both compounds have remarkable antibiotic and cytotoxic activities, but in addition, trichodermin is highly phytotoxic, while HA lacks this activity when analyzed in vivo. Analysis of Fusarium trichothecene intermediates led to the conclusion that most of them, with the exception of the hydrocarbon precursor trichodiene (TD), have a detectable phytotoxic activity which is not directly related to the structural complexity of the intermediate. In the present work, the HA intermediate 12,13-epoxytrichothec-9-ene (EPT) was produced by expression of the T. arundinaceum
tri4 gene in a transgenic T. harzianum strain that already produces TD after transformation with the T. arundinaceum
tri5 gene. Purified EPT did not show antifungal or phytotoxic activity, while purified HA showed both antifungal and phytotoxic activities. However, the use of the transgenic T. harzianum
tri4 strain induced a downregulation of defense-related genes in tomato plants and also downregulated plant genes involved in fungal root colonization. The production of EPT by the transgenic tri4 strain raised levels of erg1 expression and reduced squalene accumulation while not affecting levels of ergosterol. Together, these results indicate the complex interactions among trichothecene intermediates, fungal antagonists, and host plants. 相似文献
239.
Qualitative HPLC‐DAD/ESI‐TOF‐MS Analysis,Cytotoxic, and Apoptotic Effects of Croatian Endemic Centaurea ragusina L. Aqueous Extracts 下载免费PDF全文
Centaurea ragusina L., an endemic Croatian plant species, revealed a good cytotoxic activity of aqueous extracts (AE) on human bladder (T24) and human glioblastoma (A1235) cancer cell lines. The chemical constituents were tentatively identified using high performance liquid chromatography HPLC‐DAD/ESI‐TOF‐MS in negative ionization mode. The main compounds of herba extract were sesquiterpene lactones: solstitialin A 3,13‐diacetate and epoxyrepdiolide; organic acid: quinic acid. The main compounds of flower extract were organic acids: quinic acid, citric acid, and malic acid; sesquiterpene lactone: cynaropicrin; phenolic compounds: chlorogenic acid and phenylpropanoid: syringin. The AE of C. ragusina were investigated for correlation of their effects on human bladder (T24) and human glioblastoma (A1235) cancer cell lines using the MTT assay. Although both extracts showed significant dose‐ and time‐dependent cytotoxic activity against both cancer cell lines, the flower extract exhibited slightly higher activity. In order to determine type of cell death induced by treatment, cell lines were exposed subsequently to a treatment with both flower and herba AE. The majority of the cells died by induced apoptosis treatment. Flower AE (26.25%), compared to a leaf AE (22.15%) showed slightly higher percentage of an apoptosis in T24 cells, when compared to a non‐treated cells (0.04%). 相似文献
240.
Correlating Molecular Phylogeny with Venom Apparatus Occurrence in Panamic Auger Snails (Terebridae)
Mand? Holford Nicolas Puillandre Maria Vittoria Modica Maren Watkins Rachel Collin Eldredge Bermingham Baldomero M. Olivera 《PloS one》2009,4(11)
Central to the discovery of neuroactive compounds produced by predatory marine snails of the superfamily Conoidea (cone snails, terebrids, and turrids) is identifying those species with a venom apparatus. Previous analyses of western Pacific terebrid specimens has shown that some Terebridae groups have secondarily lost their venom apparatus. In order to efficiently characterize terebrid toxins, it is essential to devise a key for identifying which species have a venom apparatus. The findings presented here integrate molecular phylogeny and the evolution of character traits to infer the presence or absence of the venom apparatus in the Terebridae. Using a combined dataset of 156 western and 33 eastern Pacific terebrid samples, a phylogenetic tree was constructed based on analyses of 16S, COI and 12S mitochondrial genes. The 33 eastern Pacific specimens analyzed represent four different species: Acus strigatus, Terebra argyosia, T. ornata, and T. cf. formosa. Anatomical analysis was congruent with molecular characters, confirming that species included in the clade Acus do not have a venom apparatus, while those in the clade Terebra do. Discovery of the association between terebrid molecular phylogeny and the occurrence of a venom apparatus provides a useful tool for effectively identifying the terebrid lineages that may be investigated for novel pharmacological active neurotoxins, enhancing conservation of this important resource, while providing supplementary information towards understanding terebrid evolutionary diversification. 相似文献