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41.
Daniel Baranowski Bozenna Golankiewicz Wojciech Folkman Mariusz Popenda 《Nucleosides, nucleotides & nucleic acids》2013,32(10):707-719
GRAPHICAL ABSTRACT We synthesized a new 2-methyl derivative of wyosine using a multistep procedure starting from guanosine. We examined different synthetic paths and optimized the conditions for each step. Based on MD calculations and analysis of the 3 J HH and J C1′H1′ of the ribose moiety, we discovered that the sugar part adopted conformation specific for the East region rarely occurring in solution. This unusual conformational preference is probably due to steric repulsions between the methyl group at position 2 and the 5′-CH2OH group. We observed that N-glycosidic bond stability weakened 14-fold upon the introduction of the methyl group in position 2 compared with wyosine. 相似文献
42.
Fabio Casu Rebecca K. Harston Maria A. Chiacchio Giuseppe Gumina 《Nucleosides, nucleotides & nucleic acids》2013,32(3):224-235
2′-Modified inosine analogs have been synthesized from 6-chloropurine riboside via 6-dimethylaminopurine or 6-benzyloxypurine intermediates. The dimethylaminopurine intermediate was obtained via an unusually facile dimethylamine transfer from dimethylformamide. Graphical Abstract: 相似文献
43.
《Nucleosides, nucleotides & nucleic acids》2013,32(5-8):623-627
Abstract Preparation of the nucleoside analogues 1 and incorporation of 1, B = T, in deoxyribooligonucleotides by the phosphoramidite method is described. A two-step deprotection procedure was developed to reduce cleavage of the modified allylic unit. The binding properties of the modified oligonucleotides towards complementary DNA and RNA has been evaluated by Tm measurements showing a ΔTm of ?2 to ?6.5°C per modification. An oligonucleotide with two modifications at the 3′-end showed considerable resistance towards cleavage by a 3′-exonuclease. No antiviral activity against HIV-1 or HSV-1 was found for 1, B = G or T, or for any of the trihydroxy derivatives 5. 相似文献
44.
Miral V. Lunagariya Khyati P. Thakor Bharat H. Pursuwani 《Nucleosides, nucleotides & nucleic acids》2013,32(8):455-483
AbstractSquare planar mononuclear platinum(II) complexes having general formula [Pt(Ln)Cl2], (where, Ln?=?L1–4) were synthesized with neutral bidentate heterocyclic 1,3,5-trisubstituted bipyrazole based ligands. The synthesized compounds were characterized by physicochemical method such as TGA, molar conductance, micro-elemental analysis and magnetic moment, and spectroscopic method such as, FT-IR, UV–vis, 1H NMR, 13C NMR and mass spectrometry. Biological applications of the compounds were carried out using in vitro brine shrimp lethality bioassay, in vitro antimicrobial study against five different pathogens, and cellular level cytotoxicity against Schizosaccharomyces pombe (S. Pombe) cells. Pt(II) complexes were tested for DNA interaction activities using electronic absorption titration, viscosity measurements study, fluorescence quenching technique and molecular docking assay. Binding constants (Kb) of ligands and complexes were observed in the range of 0.23–1.07?×?105?M?1 and 0.51–3.13?×?105?M?1, respectively. Pt(II) complexes (I–IV) display an excellent binding tendency to biomolecule (DNA) and possess comparatively high binding constant (Kb) values than the ligands. The DNA binding study indicate partial intercalative mode of binding in complex-DNA. The gel electrophoresis activity was carried out to examine DNA nuclease property of pUC19 plasmid DNA. 相似文献
45.
Stephanie Schwalm Josef Pfeilschifter Andrea Huwiler 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2013,1831(1):239-250
Sphingosine-1-phosphate (S1P) is a pleiotropic lipid mediator that acts either on G protein-coupled S1P receptors on the cell surface or via intracellular target sites. In addition to the well established effects of S1P in angiogenesis, carcinogenesis and immunity, evidence is now continuously accumulating which demonstrates that S1P is an important regulator of fibrosis. The contribution of S1P to fibrosis is of a Janus-faced nature as S1P exhibits both pro- and anti-fibrotic effects depending on its site of action. Extracellular S1P promotes fibrotic processes in a S1P receptor-dependent manner, whereas intracellular S1P has an opposite effect and dampens a fibrotic reaction by yet unidentified mechanisms. Fibrosis is a result of chronic irritation by various factors and is defined by an excess production of extracellular matrix leading to tissue scarring and organ dysfunction. In this review, we highlight the general effects of extracellular and intracellular S1P on the multistep cascade of pathological fibrogenesis including tissue injury, inflammation and the action of pro-fibrotic cytokines that stimulate ECM production and deposition. In a second part we summarize the current knowledge about the involvement of S1P signaling in the development of organ fibrosis of the lung, kidney, liver, heart and skin. Altogether, it is becoming clear that targeting the sphingosine kinase-1/S1P signaling pathway offers therapeutic potential in the treatment of various fibrotic processes. This article is part of a Special Issue entitled Advances in Lysophospholipid Research. 相似文献
46.
《Redox report : communications in free radical research》2013,18(5):193-200
AbstractIntroductionLeptin has lipid peroxidation properties in healthy individuals. Here we aimed to study the correlation between serum-oxidized low-density lipoprotein (ox-LDL) and leptin levels in patients with type 2 diabetes. We also studied the effect of metformin therapy on the correlation between serum ox-LDL and leptin levels in patients with newly diagnosed diabetes.MethodsWe performed a cross-sectional study on two groups of patients with type 2 diabetes stratified according to (1) patients with newly diagnosed diabetes and (2) patients with long-standing diabetes plus healthy controls. Patients with newly diagnosed diabetes were followed for 3 months after the initiation of metformin therapy.ResultsPatients with type 2 diabetes had a higher serum ox-LDL, ox-LDL/LDL ratio, waist circumference, fasting blood sugars (FBSs), hemoglobin A1C (HbA1C), triglyceride, homeostatic model assessment of insulin resistance (HOMA-IR) and a lower serum leptin levels than controls. Serum ox-LDL, ox-LDL/LDL ratio (0.08 (0.08–0.12) vs. 0.06 (0.05–0.08), P < 0.001) and HOMA-IR (3.26 ± 0.23 vs. 2.93 ± 0.32; P < 0.01) were decreased when serum leptin levels (15.9 ± 1.6 vs. 21.4 ± 2.5, P < 0.01) were increased after 3 months of metformin therapy. This remained significant after multiple adjustments for age, body mass index, FBS, HbA1c, and HOMA-IR. Leptin was significantly correlated with ox-LDL/LDL ratio in controls (r = 0.78, P < 0.01), and in patients with newly diagnosed diabetes (r = 0.4, P < 0.05), after metformin therapy. There were not any correlation between leptin and ox-LDL/LDL ratio in patients with long-standing diabetes and patients with newly diagnosed diabetes before treatment.DiscussionMetformin restores the positive correlation between serum ox-LDL and leptin levels in patients with type 2 diabetes. 相似文献
47.
Fei Chen Mengxing Dong Meng Ge Lingxiang Zhu Lufeng Ren Guocheng Liu Rong Mu 《基因组蛋白质组与生物信息学报(英文版)》2013,11(1):34-40
DNA sequencing using reversible terminators, as one sequencing by synthesis strategy, has garnered a great deal of interest due to its popular application in the second-generation high-throughput DNA sequencing technology. In this review, we provided its history of development, classification, and working mechanism of this technology. We also outlined the screening strategies for DNA polymerases to accommodate the reversible terminators as substrates during polymerization; particularly, we introduced the "REAP" method developed by us. At the end of this review, we discussed current limitations of this approach and provided potential solutions to extend its application. 相似文献
48.
49.
Familial hypercholesterolemia (FH) results from impaired catabolism of plasma low density lipoproteins (LDL), thus leading to high cholesterol, atherosclerosis, and a high risk of premature myocardial infarction. FH is commonly caused by defects of the LDL receptor or its main ligand apoB, together mediating cellular uptake and clearance of plasma LDL. In some cases FH is inherited by mutations in the genes of PCSK9 and LDLRAP1 (ARH) in a dominant or recessive trait. The encoded proteins are required for LDL receptor stability and internalization within the LDLR pathway. To detect the underlying genetic defect in a family of Turkish descent showing unregular inheritance of severe FH, we screened the four candidate genes by denaturing gradient gel electrophoresis (DGGE) mutation analysis. We identified different combinatory mixtures of LDLR- and LDLRAP1-gene defects as the cause for severe familial hypercholesterolemia in this family. We also show for the first time that a heterozygous LDLR mutation combined with a homozygous LDLRAP1 mutation produces a more severe hypercholesterolemia phenotype in the same family than a homozygous LDLR mutation alone. 相似文献
50.
C. Dambrot S. van de Pas L. van Zijl B. Brändl J.W. Wang M.J. Schalij R.C. Hoeben D.E. Atsma H.M. Mikkers C.L. Mummery C. Freund 《Differentiation; research in biological diversity》2013
The generation of human induced pluripotent stem cells (hiPSCs) requires the collection of donor tissue, but clinical circumstances in which the interests of patients have highest priority may compromise the quality and availability of cells that are eventually used for reprogramming. Here we compared (i) skin biopsies stored in standard physiological salt solution for up to two weeks (ii) blood outgrowth endothelial cells (BOECs) isolated from fresh peripheral blood and (iii) children's milk teeth lost during normal replacement for their ability to form somatic cell cultures suitable for reprogramming to hiPSCs. We derived all hiPSC lines using the same reprogramming method (a conditional (FLPe) polycistronic lentivirus) and under similar conditions (same batch of virus, fetal calf serum and feeder cells). Skin fibroblasts could be reprogrammed robustly even after long-term biopsy storage. Generation of hiPSCs from juvenile dental pulp cells gave similar high efficiencies, but that of BOECs was lower. In terms of invasiveness of biopsy sampling, biopsy storage and reprogramming efficiencies skin fibroblasts appeared best for the generation of hiPSCs, but where non-invasive procedures are required (e.g. for children and minors) dental pulp cells from milk teeth represent a valuable alternative. 相似文献