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1.
Robert Van Ostrand Casey Jacobsen Alicia Delahunty Carley Stringer Ryan Noorbehesht Haidi Ahmed 《Nucleosides, nucleotides & nucleic acids》2017,36(3):181-197
Reported is an efficient synthesis of adenyl and uridyl 5′-tetrachlorophthalimido-5′-deoxyribonucleosides, and guanylyl 5′-azido-5′-deoxyribonucleosides, which are useful in solid-phase synthesis of phosphoramidate and ribonucleic guanidine oligonucleotides. Replacement of 5′-hydroxyl with tetrachlorophthalimido group was performed via Mitsunobu reaction for adenosine and uridine. An alternative method was applied for guanosine which replaced the 5′-hydroxyl with an azido group. The resulting compounds were converted to 5′-amino-5′-deoxyribonucleosides for oligonucleotide synthesis. Synthetic intermediates were tested as antimicrobials against six bacterial strains. All analogs containing the 2′,3′-O-isopropylidine protecting group demonstrated antibacterial activity against Neisseria meningitidis, and among those analogs with 5′-tetrachlorophthalimido and 5′-azido demonstrated increased antibacterial effect. 相似文献
2.
Moheshwar Sharma Yi X. Li Miroslav Ledvina Miroslav Bobek 《Nucleosides, nucleotides & nucleic acids》2013,32(9-10):1831-1852
Abstract A series of 5′-substituted analogs of toyocamycin were prepared by condensation of silylated 4-amino-6-bromo-5-cyanopyrrolo[2,3-d]pyrimidine with protected 5-azido-5-deoxy- or 5-fluoro-5-deoxyribofuranose followed by debromination and deblocking. Alternatively, 5′-azido-5′-deoxytoyocamycin was prepared by azidation of toyocamycin. Conversion of the 5-nitrile function of the toyocamycin derivatives into a carboxamide or a thiocarboxamide gave the corresponding analogs of sangivamycin or thiosangivamycin while reduction of the 5′-azido-5′-deoxy nucleosides provided 5′-amino-5′-deoxy derivatives. 相似文献
3.
《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2017,1862(5):561-571
Human 5-lipoxygenase (5-LO-WT) initiates the leukotriene (LT) biosynthesis. LTs play an important role in diseases like asthma, atherosclerosis and in many types of cancer. In this study, we investigated the 5-LO isoforms 5-LO∆13, 5-LO∆4 and 5-LOp12, lacking the exons 13, 4 or a part of exon 12, respectively. We were able to detect the mRNA of the isoforms 5-LO∆13 and 5-LOp12 in B and T cell lines as well as in primary B and T cells and monocytes. Furthermore, we found that expression of 5-LO and particularly of the 5-LO∆13 and 5-LOp12 isoforms is increased in monocytes from patients with rheumatoid arthritis and sepsis. Confocal microscopy of HEK293T cells stably transfected with tagged 5-LO-WT and/or the isoforms revealed that 5-LO-WT is localized in the nucleus whereas all isoforms are located in the cytosol. Additionally, all isoforms are catalytically inactive and do not seem to influence the specific activity of 5-LO-WT. S271A mutation in 5-LO-WT and treatment of the cells with sorbitol or KN-93/SB203580 changes the localization of the WT enzyme to the cytosol. Despite colocalization with the S271A mutant, the isoforms did not affect LT biosynthesis. Analysis of the phosphorylation pattern of 5-LO-WT and all the isoforms revealed that 5-LOp12 and 5-LO∆13 are highly phosphorylated at Ser271 and 5-LOp12 at Ser523. Furthermore, coexpression of the isoforms inhibited or stimulated 5-LO-WT expression in transiently and stably transfected HEK293T cells suggesting that the isoforms have other functions than canonical LT biosynthesis. 相似文献
4.
David Garciadiego-Cázares Hilda I. Aguirre-Sánchez René F. Abarca-Buis Juan B. Kouri Cristina Velasquillo Clemente Ibarra 《PloS one》2015,10(5)
The Integrin β1 family is the major receptors of the Extracellular matrix (ECM), and the synthesis and degradation balance of ECM is seriously disrupted during Osteoarthritis (OA). In this scenario, integrins modify their pattern expression and regulate chondrocyte differen-tiation in the articular cartilage. Members of the Transforming growth factor beta (Tgf-β) Su-perfamily, such as Growth differentiation factor 5 (Gdf-5) and Bone morphogenetic protein 7 (Bmp-7), play a key role in joint formation and could regulate the integrin expression during chondrocyte differentiation and osteoarthritis progression in an experimental OA rat model. Decrease of α5 integrin expression in articular cartilage was related with chondrocyte dedif-ferentiation during OA progression, while increase of α1, α2, and α3 integrin expression was related with fibrous areas in articular cartilage during OA. Hypertrophic chondrocytes expressedαV integrin and was increased in the articular cartilage of rats with OA. Integrin expression during chondrocyte differentiation was also analyzed in a micromass culture system of mouse embryo mesenchymal cells, micromass cultures was treated with Gdf-5 or Bmp-7 for 4 and 6 days, respectively. Gdf-5 induced the expression of theα5 sub-unit, while Bmp-7 induced the expression of the αV sub-unit. This suggests a switch in signaling for prehypertrophic chondrocyte differentiation towards hypertrophy, where Gdf-5 could maintain the articular chondrocyte phenotype and Bmp-7 would induce hypertrophy. Decrease of Ihh expression during late stages of OA in rat model suggest that the ossification in OA rat knees and endochondral ossification could be activated by Bmp-7 and αV integrin in absence of Ihh. Thus, chondrocyte phenotype in articular cartilage is similar to prehypetrophic chondrocyte in growth plate, and is preserved due to the presence of Indian hedgehog (Ihh), Gdf-5 and α5 integrin to maintain articular cartilage and prevent hy-pertrophy. 相似文献
5.
6.
《Phytochemistry》1996,42(5):1259-1262
Methyl 5′,5′,5′-trifluorojasmonate was synthesized as an antimetabolic analogue of methyl jasmonate. It induced potato tuber formation more effectively than methyl jasmonate and inhibited the growth of rice seedlings and the germination of lettuce and radish seeds. These results suggest that epijasmonic acid itself has potato tuber-inducing activity and that the hydroxyl group of tuberonic acid is not necessary for this activity. 相似文献
7.
Jasenka Matulic-Adamic Peter Haeberli Anthony B. DiRenzo Victor R. Mokler Lara Maloney Leonid Beigelman 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1933-1950
Abstract Novel 5′-amino-5′-deoxy-2′-O-methyl uridine, guanosine and adenosine 3′-O-phosphoramidites 5, 11, and 20, as well as protected 5′-mercapto-5′-deoxy-2′-O-methyl uridine 3′-O-phosphoramidite 23 were synthesized from 2′-O-methyl nucleosides. These analogs were incorporated at the 5′-ends of hammerhead ribozymes to evaluate achiral bridging 5′-N- phosphoramidates and 5′-S-phosphorothioates as alternatives for non- bridging phosphorothioates commonly used for end stabilization against nucleases. Oligonucleotide synthesis and deprotection conditions were optimized for better yields of these modified ribozymes. 相似文献
8.
Guy Tourigny Allan L. Stuart Irena Ekiel Philip J. Aduma Sagar V. Gupta 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1189-1200
Abstract The molecular conformations of 3′- and 5′-azido and amino derivatives of 5-methoxymethyl-2′-deoxyuridine, 1, were investigated by nmr. The glycosidic conformation of 5-methoxymethyl-5′-amino-2′,5′-dideoxy-uridine, 5 had a considerable population of the syn form. The 5′-derivatives show a preference for the S conformation of the furanose ring as in 1. In contrast, the 3′-derivatives show preference for the N conformation. For 5-methoxymethyl-3′-amino-2′,3′-dideoxyuridine, 3, the shift towards the N state is pH dependent. The preferred conformation for the exocyclic (C4′,C5′) side chain is g+ for all compounds except 5 which has a strong preference for the t rotamer (79%). Compounds 1, 3 and 5 inhibited growth of HSV-1 by 50% at 2, 18 and 70 μg/ml respectively, whereas 2 and 4 were not active up to 256 μg/ml (highest concentration tested). The compounds were not cytotoxic up to 3,000 μM. 相似文献
9.
Subha R. Das 《Nucleosides, nucleotides & nucleic acids》2013,32(10):668-677
To extend the potential of 5′-noraristeromycin (and its enantiomer) as potential antiviral candidates, the enantiomers of the carbocyclic 5′-nor derivatives of 5′-methylthio-5′-deoxyadenosine and 5′-phenylthio-5′-deoxyadenosine have been synthesized and evaluated. None of the compounds showed meaningful antiviral activity. 相似文献
10.
Two uridine 2′,3′-cyclic monophosphate (cUMP) derivatives, 5′-deoxy (DcUMP) and 5′-O-methyl (McUMP), were studied by means
of quantum chemical methods. Aqueous solvent effects were estimated based on the isodensity-surface polarized-continuum model
(IPCM). Gas phase calculations revealed only slight energy differences between the syn- and anti-conformers of both compounds: the relative energies of the syn-structure are −0.9 and 0.2 kcal mol-1 for DcUMP and McUMP, respectively. According to the results from the IPCM calculations, however, both syn-conformers become about 14 kcal mol-1 more stable in aqueous solution than their corresponding anti-structures. Additionally, the effects of a countercation and protonation on DcUMP were studied, revealing that the syn-structure is also favored over the anti-one for these systems. 相似文献
11.
J.-L. Girardet G. Gosselin C. Périgaud J. Balzarini E. De Clercq J.-L. Imbach 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):645-647
Abstract Several new prodrugs of 5-fluoro-2′-deoxyuridine 5′-monophosphate and 3′,5′-cyclic monophosphate were synthesized and their antitumor activities were evaluated in vitro. 相似文献
12.
J. Tomasz 《Nucleosides, nucleotides & nucleic acids》2013,32(1):51-61
Abstract A simple procedure is described for the preparation of the title compounds 1, 8 and 9. 3′-3′ or 3′-5′ or 5′-5′ TpT was reacted with a twofold molar excess of TPS in anhydrous DMF, at room temperature, for 5 min, followed by a 1 min in situ treatment of the reaction mixture with excess 7.0 N NH4OH, at 0°C. The alkaline hydrolysis of 1, 8 and 9 proceeds without the assistance of 3′- and 5′-hydroxyl groups resulting in equimolar mixtures of thymidine (4) and thymidine 3′-phosphoramidate (6) (for the 3′-3′ isomer) or thymidine 5′-phosphoramidate (7) (for the 5′-5′ isomer) or 6 and 7 in equal quantities (for the 3′-5′ isomer). 相似文献
13.
Caroline Spenlé Patricia Simon-Assmann Gertraud Orend Jeffrey H. Miner 《Cell Adhesion & Migration》2013,7(1):90-100
Laminins (LM) are extracellular matrix molecules that contribute to and are required for the formation of basement membranes. They participate in the modulation of epithelial/mesenchymal interactions and are implicated in organogenesis and maintenance of organ homeostasis. Among the LM molecules, the LM α5 chain (LMα5) is one of the most widely distributed LM in the developing and mature organism. Its presence in some basement membranes during embryogenesis is absolutely required for maintenance of basement membrane integrity and thus for proper organogenesis. LMα5 also regulates the expression of genes important for major biological processes, in part by repressing or activating signaling pathways, depending upon the physiological context. 相似文献
14.
Marie-France Carlier 《Molecular and cellular biochemistry》1982,47(2):97-113
Summary GTP hydrolysis associated with polymerization is a distinctive feature of microtubule assembly. This reaction may be fundamentally linked to the dynamic properties of microtubules in vivo. Kinetic analysis of the connection between microtubule assembly and associated GTP hydrolysis indicates that these two events are kinetically uncoupled, GTP hydrolysis occurring after tubulin incorporation in the microtubule. As a consequence, the combination of the diffusionnal incorporation of GTP in microtubules at steady-state and of subsequent GTP hydrolysis results in the formation of a steady-state GTP cap at microtubule ends. The interplay between GTP and GDP at microtubule ends is examined. Inhibition by GDP of steady-state GTP hydrolysis at microtubule ends and of microtubule elongation is understood within a tight reversible binding of GDP at microtubule ends generating inactive elongation sites. Nucleotides are freely exchangeable at microtubule ends. This result indicates that the nature of the nucleotide present at microtubule ends must be considered in a model for microtubule assembly.These data are pooled in order to define the general features of a model describing microtubule assembly and treadmilling in terms somewhat different from previously proposed models. 相似文献
15.
Male New Zealand White rabbits were divided into three groups: (I) control, (II) high-fat-diet (HFD) fed, and (III) HFD fed+selenium
supplemented. After 3 mo of treatment, there was a significant increase in serum cholesterol and triglycerides in the HFD-fed
group as compared to the control. However in the selenium (Se)-supplemented group, the levels of serum cholesterol and triglycerides
were significantly less as compared to group II. HFD feeding resulted in decreased serum Se levels, but supplementation of
dietary Se along with HFD, as in group III, showed an apparent increase in its levels. The Se-dependent glutathione peroxidase
(GSH-Px) activity in the liver and the aorta increased significantly in HFD-fed animals and also showed an additional significant
increase on Se supplementation. Both serum T3 and T4 levels showed a significant decrease on HFD feeding. However, supplementation of Se led to a significant increase in the
levels of these parameters viz-à-viz HFD-fed animals. HFD feeding significantly decreased the activity of type I iodothyronine
5′-deiodinase (5′-DI) in the liver from group II rats. On supplementation of Se along with HFD, the activity increased in
the liver. However, there was no significant change in its activity in the aorta. The 5′-DI activity in the thyroid showed
an opposite trend in comparison with peripheral tissues (i.e., liver). The important finding of this study is that in the
hyperlipidemic state, deiodinase in the thyroid behaves in a different manner as compared to its activity in extrathyroidal
tissues. 相似文献
16.
SL Gupton D Riquelme SK Hughes-Alford J Tadros SS Rudina R O Hynes D Lauffenburger FB Gertler 《The Journal of cell biology》2012,198(4):657-676
Mena is an Ena/VASP family actin regulator with roles in cell migration, chemotaxis, cell-cell adhesion, tumor cell invasion, and metastasis. Although enriched in focal adhesions, Mena has no established function within these structures. We find that Mena forms an adhesion-regulated complex with α5β1 integrin, a fibronectin receptor involved in cell adhesion, motility, fibronectin fibrillogenesis, signaling, and growth factor receptor trafficking. Mena bound directly to the carboxy-terminal portion of the α5 cytoplasmic tail via a 91-residue region containing 13 five-residue "LERER" repeats. In fibroblasts, the Mena-α5 complex was required for "outside-in" α5β1 functions, including normal phosphorylation of FAK and paxillin and formation of fibrillar adhesions. It also supported fibrillogenesis and cell spreading and controlled cell migration speed. Thus, fibroblasts require Mena for multiple α5β1-dependent processes involving bidirectional interactions between the extracellular matrix and cytoplasmic focal adhesion proteins. 相似文献
17.
Steenhard BM Zelenchuk A Stroganova L Isom K St John PL Andrews GK Peterson KR Abrahamson DR 《PloS one》2011,6(9):e23926
Laminin α5 is required for kidney glomerular basement membrane (GBM) assembly, and mice with targeted deletions of the Lama5 gene fail to form glomeruli. As a tool to begin to understand factors regulating the expression of the LAMA5 gene, we generated transgenic mice carrying the human LAMA5 locus in a bacterial artificial chromosome. These mice deposited human laminin α5 protein into basement membranes in heart, liver, spleen and kidney. Here, we characterized two lines of transgenics; Line 13 expressed ~6 times more LAMA5 than Line 25. Mice from both lines were healthy, and kidney function and morphology were normal. Examination of developing glomeruli from fetal LAMA5 transgenics showed that the human transgene was expressed at the correct stage of glomerular development, and deposited into the nascent GBM simultaneously with mouse laminin α5. Expression of human LAMA5 did not affect the timing of the mouse laminin α1-α5 isoform switch, or that for mouse laminin β1-β2. Immunoelectron microscopy showed that human laminin α5 originated in both glomerular endothelial cells and podocytes, known to be origins for mouse laminin α5 normally. Notably, in neonatal transgenics expressing the highest levels of human LAMA5, there was a striking reduction of mouse laminin α5 protein in kidney basement membranes compared to wildtype, and significantly lower levels of mouse Lama5 mRNA. This suggests the presence in kidney of a laminin expression monitor, which may be important for regulating the overall production of basement membrane protein. 相似文献
18.
19.
Miron VR Bauermann L Morsch AL Zanin RF Corrêa M da Silva AC Mazzanti C Morsch VM Lunkes GI Schetinger MR 《Molecular and cellular biochemistry》2007,298(1-2):101-107
The activity of the enzymes NTPDase and 5′-nucleotidase was studied in both diabetes mellitus and an associated model of iron-overload.
Rats were divided in five groups: citrate (CC), saline (S), diabetic (D), iron-overload (IO), and diabetic iron-overload (DIO).
Diabetes was induced with alloxan (150 mg/kg), and iron-overload was induced with iron-dextran (10 intramuscular applications
of ±80 mg/kg). The enzymatic activities were evaluated in the platelets. The results demonstrated an increase in the activity
of NTPDase with substrates ATP and ADP (60% and 120%, respectively; P < 0.001), and 5′-nucleotidase (60%, P < 0.001). This increase was more intense in the IO and DIO groups. The results obtained in vitro showed an activation in
ATP, ADP, and AMP hydrolysis between 1 μM and 1,000 μM ferric nitrate concentrations, being more pronounced at 100 μM and
decreasing at 1,000 μM. We concluded that diabetes mellitus in association with iron-overload increased the hydrolysis of
adenine nucleotides in platelets, contributing to the abnormalities found in these pathological conditions. 相似文献
20.
Enzymatic activity and substrate specificity of recombinant tomato β-galactosidases 4 and 5 总被引:1,自引:0,他引:1
The open reading frames of tomato β-galactosidase (TBG) 4 and 5 cDNAs were expressed in yeast, and the enzymes properties
and substrate specificities were investigated. The two enzymes had peak activities between pH 4–4.5 and 37–45°C. TBG4 specifically
hydrolyzed β-(1→4) and 4-linked galactooligosaccharides. TBG5 had a strong preference to hydrolyze β-(1→3) and β-(1→6)-linked
galactooligosaccharides. Exo-β-galactanase activity of the TBG enzymes was measured by determining the release of galactosyl
residues from native tomato cell wall fractions throughout fruit development and ripening. Both TBGs released galactose from
all of the fractions and stages tested. TBG4 activity was highest using chelator soluble pectin and alkali soluble pectin
at the turning stage of ripening. Using aminopyrene trisulfonate labeled substrates, TBG4 was the only enzyme with strong
exo-β-(1→4)-galactanase activity on 5 mer or greater galactans. TBG4 and TBG5 were both able to degrade galactosylated rhamnogalacturonan.
Neither enzyme was able to degrade galactosylated xyloglucan. 相似文献