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71.
Abstract Several 6- and 7-substituted quinazoline-2, 4-(1H, 3H)-diones (1–7) have been ribosylated with 1-0-acetyl-–2, 3, 5-tri-0-benzoyl-β-D-ribofuranose (8)via the “silyl”-method and Lewis acid catalysis in a highly regioselective manner to give the corresponding protected N-1 ribosides 9–15. Debenzoylation to the free nucleosides 16–22 was achieved by sodium methoxide. Thiation of 9–15 by Lawesson's reagent effected the conversion of the 4-oxo into the 4-thioxo function (23–29). Removal of the sugar protecting groups in these derivatives worked best with potassium carbonate in anhydrous MeOH to form in high yields 30–35. Treatment of the peracylated 4-thioxo quinazoline nucleosides with methanolic ammonia resulted in deacylation of the sugar moiety and in displacement of the sulfur function to give the corresponding 4-amino-1-β-D-ribofuranosylquinazolin-2(1H)-ones 36–41. The newly synthesized, nucleosides have been characterized by elemental analysis, UV- and 1H-NMR-spectra. 相似文献
72.
Katalin Kariko Nancy L. Reichenbach Robert J. Suhadolnik Ramamurthy Charubala Wolfgang Pfleiderer 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):497-500
Abstract Enzymatically and chemically synthesized cordycepin analogs of 2–5A? trimer and tetramer were found to be biologically active as protein synthesis inhibitors in intact cultured human fibroblast and murine L929 cells 1,2. In rabbit reticulocyte lysates, the cordycepin tetramer analog of 2–5A inhibits protein synthesis through binding to and activation of RNase L3. Our present results using L929 cell extracts provide direct evidence that the cordycepin analogs of 2–5A can bind to and activate RNase L. 相似文献
73.
Robert J. Suhadolnik Paul W. Doetsch Yair Devash Earl E. Henderson Ramamurthy Charubala Wolfgang Pfleiderer 《Nucleosides, nucleotides & nucleic acids》2013,32(4):351-366
Abstract The effect of the 2′,5′-adenylate and cordycepin trimer cores on DNA and protein synthesis in human umbilical cord lymphocytes, lymphoblasts, peripheral blood lymphocytes and Epstein-Barr virus infected lymphocytes and their metabolism in tissue culture medium have been studied. [32P]Adenylate and [32P]- and [3H]cordycepin trimer cores were synthesized either enzymatically or chemically and added to cells in culture. The half-lives of the 2′,5′-A3 core and 2′,5′-3′dA3 core in tissue culture were 3 and 17 hr, respectively. Chromatographic analysis of the TCA-soluble extracts of the lymphocytes and lymphoblasts treated with 2′,5′-[3H]A3 showed that 0.25% of the 32P was identified as AMP, ADP, ATP and inorganic phosphate. By the more sensitive 2′,5′-p3A4[32P]pCp radiobinding assay, 2′,5′-A3 was detected in the TCA supernatants; however, there was no 5′-rephosphorylation. With the [3H]- and [32P]cordycepin trimer core, 0.55% and 1.3% of the radioactivity was in the TCA soluble extracts. Although there was no 5′-rephosphorylation as determined by radiobinding assay, the intact cordycepin trimer core was detected by tlc, radiobinding assay, and HPLC. Furthermore, in two experiments, the concentration of the cordycepin trimer core bound to or taken up by the lymphocytes was three-fold greater than the concentration in the medium. 2′,5′-A3 and 2′,5′-3′dA3 cores were both antimitogenic, but did not inhibit protein synthesis. 相似文献
74.
Abstract The use of the base labile 2-(p-nitrophenyl)-ethoxycarbonyl (NPEOC), 2-(2,4-dinitrophenyl)-ethoxycarbonyl (DNPEOC) and 2-cyanoethoxy-carbonyl (CEOC) group for hydroxyl protection of the sugar moiety in ribo-nucleosides and deoxyribonucleosides are described and discussed. 相似文献
75.
Najim A. Al-Masoudi Wolfgang Pfleiderer Hassan B. Lazrek 《Nucleosides, nucleotides & nucleic acids》2013,32(7):687-699
Abstract The chemical syntheses of 1-(2,3,4,6-tetra-0-acety]-5-thio-β-D-glucopyranosyl)-6-azauracil (4) and the 5-bromo analogue 6 are described. Deblocking of 4 and 6 with sodium methoxide afforded the free nucleosides 5 and 7, respetively. Treatment of 6 with benzylmercaptan in basic medium led to the formation of 6-benzylthio-1-((2,3,4,6-tetra-0-acetyl-5-thio-β-D-glucopyranosyl)-6-azauracil (8), in good yield, which was deblocked to 9 on treatment with sodium methoxide. Reaction of 6 with benzlamine gave 5-benzylamino-1-(5-thio-β-D-glucopyranosyl)-6-azauracil (10). 相似文献
76.
Christoph Henke Wolfgang Pfleiderer 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1665-1706
The 5 α-D-arabinofuranosylnucleosides α-araU (15), α-araT (18), α-araC (22), α-araA (25), and α-araG (28) have been synthesized by the modified silyl-method. The amino groups at the nucleobases and the 2′-hydroxy group at the sugar moiety were protected by the 2-(4-nitro-phenyl) ethoxycarbonyl (npeoc) group (37-40) and the amide function in α-araG was additionally blocked by the 2-(4-nitrophenyl)ethyl group (63) to improve solubility in organic solvents. Mono-and dimethoxytritylation of the 5′-OH group was performed in the usual manner to give 41-48, 64, and 65 in high yields and further substitution of the 3′-OH group led to the monomeric building blocks 66-75 as well as the 3′-O-succinoyl derivatives 76-85 functioning as starting units in solid-support oligonucleotide synthesis. A large number of oligo-α-arabinonucleotides have been prepared on modified CPG-material applying the npeoc/npe strategy as a very efficient synthetic tool for highly purified, homogenous oligomers. Hybridizations between α-arabinonucleotide strands revealed in analogy to earlier findings an antiparallel orientation whereas the combination of an oligo-α-D-arabinonucleotide with a complementary oligo-2′-deoxy-β-D-ribofuranosylnucleotide showed base-pairing only if a parallel polarity was present. The advantages in oligo-α-arabinonucleotide synthesis were furthermore demonstrated by the synthesis of the tα-ANA his a structural analog of the natural tRNA his of the phage T5. 相似文献
77.
Duijnisveld BJ Bigot A Beenakker KG Portilho DM Raz V van der Heide HJ Visser CP Chaouch S Mamchaoui K Westendorp RG Mouly V Butler-Browne GS Nelissen RG Maier AB 《Arthritis research & therapy》2011,13(6):R207-10
Introduction
Chronic inflammation is a profound systemic modification of the cellular microenvironment which could affect survival, repair and maintenance of muscle stem cells. The aim of this study was to define the role of chronic inflammation on the regenerative potential of satellite cells in human muscle.Methods
As a model for chronic inflammation, 11 patients suffering from rheumatoid arthritis (RA) were included together with 16 patients with osteoarthritis (OA) as controls. The mean age of both groups was 64 years, with more females in the RA group compared to the OA group. During elective knee replacement surgery, a muscle biopsy was taken from the distal musculus vastus medialis. Cell populations from four RA and eight OA patients were used for extensive phenotyping because these cell populations showed no spontaneous differentiation and myogenic purity greater than 75% after explantation.Results
After mononuclear cell explantation, myogenic purity, viability, proliferation index, number of colonies, myogenic colonies, growth speed, maximum number of population doublings and fusion index were not different between RA and OA patients. Furthermore, the expression of proteins involved in replicative and stress-induced premature senescence and apoptosis, including p16, p21, p53, hTERT and cleaved caspase-3, was not different between RA and OA patients. Mean telomere length was shorter in the RA group compared to the OA group.Conclusions
In the present study we found evidence that chronic inflammation in RA does not affect the in vitro regenerative potential of human satellite cells. Identification of mechanisms influencing muscle regeneration by modulation of its microenvironment may, therefore, be more appropriate. 相似文献78.
Jeroen Slikkerveer Pieter A Dijkmans Gertjan T Sieswerda Pieter AFM Doevendans Arie PJ van Dijk Freek WA Verheugt Thomas R Porter Otto Kamp 《Trials》2008,9(1):1-7
Background
The CONSORT Statement provides recommendations for reporting randomized controlled trials. We assessed the extent to which leading medical journals that publish reports of randomized trials incorporate the CONSORT recommendations into their journal and editorial processes.Methods
This article reports on two observational studies. Study 1: We examined the online version of 'Instructions to Authors' for 165 high impact factor medical journals and extracted all text mentioning the CONSORT Statement or CONSORT extension papers. Any mention of the International Committee of Medical Journal Editors (ICMJE) or clinical trial registration were also sought and extracted. Study 2: We surveyed the editor-in-chief, or editorial office, for each of the 165 journals about their journal's endorsement of CONSORT recommendations and its incorporation into their editorial and peer-review processes.Results
Study 1: Thirty-eight percent (62/165) of journals mentioned the CONSORT Statement in their online 'Instructions to Authors'; of these 37% (23/62) stated this was a requirement, 63% (39/62) were less clear in their recommendations. Very few journals mentioned the CONSORT extension papers. Journals that referred to CONSORT were more likely to refer to ICMJE guidelines (RR 2.16; 95% CI 1.51 to 3.08) and clinical trial registration (RR 3.67; 95% CI 2.36 to 5.71) than those journals which did not. Study 2: Thirty-nine percent (64/165) of journals responded to the on-line survey, the majority were journal editors. Eighty-eight percent (50/57) of journals recommended authors comply with the CONSORT Statement; 62% (35/56) said they would require this. Forty-one percent (22/53) reported incorporating CONSORT into their peer-review process and 47% (25/53) into their editorial process. Eighty-one percent (47/58) reported including CONSORT in their 'Instructions to Authors' although there was some inconsistency when cross checking information on the journal's website. Sixty-nine percent (31/45) of journals recommended authors comply with the CONSORT extension for cluster trials, 60% (27/45) for harms and 42% (19/45) for non-inferiority and equivalence trials. Few journals mentioned these extensions in their 'Instructions to Authors'.Conclusion
Journals should be more explicit in their recommendations and expectations of authors regarding the CONSORT Statement and related CONSORT extensions papers. 相似文献79.
A three-year survey (1997–99) was carried out on organically reared sheep flocks throughout Sweden. The aim was to determine the prevalence and intensity of nematode infections and to establish relationships between sheep management practices and parasite infections. Faecal samples from ewes and lambs were collected from 152 organic flocks around lambing-time and during the grazing-period for analysis. Results were compared with the different management practices that farmers use to prevent parasitism in their flocks. A high proportion of the flocks was infected with nematodes. The most prevalent species were Haemonchus contortus, Teladorsagia circumeincta, Trichostrongylus axei, T. colubriformis and Chabertia ovina and infections progressively increased during summer in lambs grazing on permanent pastures. Severity of parasitic infection in lambs was highly dependent on egg output from the ewes. H. contortus was found in 37% of the flocks, even at latitudes approximating the Polar Circle. Nematodirus battus was recorded for the first time in Sweden during the course of this study. Lambs turned out onto permanent pasture showed higher nematode faecal egg counts (epg) than lambs that had grazed on pastures, which had not carried sheep the previous year. This beneficial effect of lambs grazing non-infected pastures persisted if the ewes were treated with an anthelmintic before turn-out and if the lambs were kept on pastures of low infectivity after weaning. In lambs, the prevalence and the magnitude of their egg counts were higher during autumn in flocks where lambs were slaughtered after 8 months of age, compared with flocks where all lambs were slaughtered before this age. These results will be used in providing advice to farmers of ways to modify their flock management in order to minimise the use of anthelmintics, but at the same time efficiently produce prime lambs. 相似文献
80.
C Monde S Syampungani A Rico PJ van den Brink 《African Journal of Aquatic Science》2017,42(3):235-243
The potential of red claw crayfish and hybrid African catfish (Clarias gariepinus and Clarias ngamensis) as predators for Schistosoma host snails was evaluated in 2014 by monitoring the consumption of snails by crayfish and catfish in experimental tanks over time under laboratory conditions. After 15 days, both crayfish and catfish had significantly reduced the populations of Bulinus globosus. Crayfish consumed 6.9 snails d?1, whereas catfish consumed 5.9 snails d?1. However, when supplied with an alternative prey, Melanoides tuberculata (100 individuals per tank), crayfish clearly preferred M. tuberculata (100% consumed over seven days) to B. globosus (100 individuals per tank) (54% consumed over the same period). Catfish, conversely, did not have a clear preference for either prey species, consuming 77% and 88% of M. tuberculata and B. globosus, respectively. It was also observed that young catfish were more efficient predators than older ones, because of ontogenetic shifts in their diet with age. Hybrid catfish retain the molluscivorous characteristics of their parent stock and red claw crayfish also preys on Schistosoma host snails. However, the effectiveness of both predators is affected by the presence of an alternative prey. Therefore, under suitable conditions, these species can be considered for biological control of schistosomiasis transmission. 相似文献