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Nucleosides, Nucleotides & Nucleic Acids

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https://www.readbyqxmd.com/read/28524722/lesch-nyhan-disease-in-two-families-from-chilo%C3%A3-island-with-mutations-in-the-hprt1-gene
#1
Khue Vu Nguyen, Sebastian Silva, Monica Troncoso, Robert K Naviaux, William L Nyhan
Lesch-Nyhan disease (LND) is a rare X-linked inherited neurogenetic disorder of purine metabolism in which the enzyme, hypoxanthine-guanine phosphoribosyltransferase (HGprt) is defective. The authors report two independent point mutations leading to splicing errors: IVS 2 +1G>A, c.134 +1G>A, and IVS 3 +1G>A, c.318 +1G>A in the hypoxanthine-phosphoribosyltransferase1 (HPRT1) gene which result in exclusion of exon 2 and exon 3 respectively, in the HGprt enzyme protein from different members of two Chiloé Island families...
May 19, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28498075/the-impact-of-6-thioguanine-incorporation-into-dna-on-the-function-of-dna-methyltransferase-dnmt3a
#2
Olga V Kirsanova, Alexander V Sergeev, Ivan S Yasko, Elizaveta S Gromova
The incorporation of chemotherapeutic agent 6-thioguanine ((S)G) into DNA is a prerequisite for its cytotoxic action. This modification of DNA impedes the activity of enzymes involved in DNA repair and replication. Here, using hemimethylated DNA substrates we demonstrated that DNA methylation by Dnmt3a-CD is reduced if DNA is damaged by the incorporation of (S)G into one or two CpG sites separated by nine base pairs. An increase in the number of (S)G substitutions did not enhance the effect. Dnmt3a-CD binding to either of (S)G-containing DNA substrates was not distorted...
May 12, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28486036/comparison-of-dna-fragments-as-donor-dnas-upon-sequence-conversion-of-cleaved-target-dna
#3
Tetsuya Suzuki, Takashi Imada, Yasuo Komatsu, Hiroyuki Kamiya
Pinpoint sequence alteration (genome editing) by the combination of the site-specific cleavage of a target DNA and a donor nucleic acid has attracted much attention and the sequence of the target DNA is expected to be changed to that of a donor nucleic acid. In most cases, oligodeoxyribonucleotides (ODNs) and plasmid DNAs have been used as donors. However, a several hundred-base single-stranded (ss) DNA fragment and a 5'-tailed duplex (TD) accomplished the desired sequence changes without DNA cleavage, and might serve as better donors for the cleaved target DNA than ODNs and plasmid DNAs...
May 9, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28475413/unexpected-transformation-of-black-hole-quenchers-in-electrophoretic-purification-of-the-fluorescein-containing-taqman-probes
#4
Vladimir A Ryabinin, Elena V Kostina, Alexander N Sinyakov
The fluorescence quenchers BHQ1 and BHQ2 can be modified by trace amounts of ammonium persulfate, used for initiating gel polymerization, in electrophoretic purification of TaqMan probes using a denaturing polyacrylamide gel. The case study of BHQ1 quencher has demonstrated that a Boyland-Sims reaction proceeds in the presence of ammonium persulfate to give the corresponding sulfate. The absorption maximum of the resulting quencher shifts to the short-wavelength region relative to the absorption maximum of the initial BHQ1...
May 5, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28362164/determination-of-restriction-enzyme-activity-when-cutting-dna-labeled-with-the-toto-dye-family
#5
April Maschmann, Kristy L Kounovsky-Shafer
Optical mapping, a single DNA molecule genome analysis platform that can determine methylation profiles, uses fluorescently labeled DNA molecules that are elongated on the surface and digested with a restriction enzyme to produce a barcode of that molecule. Understanding how the cyanine fluorochromes affect enzyme activity can lead to other fluorochromes used in the optical mapping system. The effects of restriction digestion on fluorochrome labeled DNA (Ethidium Bromide, DAPI, H33258, EthD-1, TOTO-1) have been analyzed previously...
March 31, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28332916/tautomeric-equilibria-of-iso-guanine-and-related-purine-analogs
#6
Nilesh B Karalkar, Kshitij Khare, Robert Molt, Steven A Benner
Nucleobase pairs in DNA match hydrogen-bond donor and acceptor groups on the nucleobases. However, these can adopt more than one tautomeric form, and can consequently pair with nucleobases other than their canonical complements, possibly a source of natural mutation. These issues are now being re-visited by synthetic biologists increasing the number of replicable pairs in DNA by exploiting unnatural hydrogen bonding patterns, where tautomerism can also create mutation. Here, we combine spectroscopic measurements on methylated analogs of isoguanine tautomers and tautomeric mixtures with statistical analyses to a set of isoguanine analogs, the complement of isocytosine, the 5th and 6th "letters" in DNA...
March 23, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28323527/design-synthesis-and-anticancer-evaluation-of-novel-pyrazole-pyrazolo-3-4-d-pyrimidine-and-their-glycoside-derivatives
#7
Ibrahim F Nassar, Ahmed F El Farargy, Fathy M Abdelrazek, Nasser S M Ismail
The chalcone derivatives 3a,b were cyclized upon reaction with thiourea to give the pyrazolo[3,4-d]pyrimidine derivatives 5a,b. Condensation of 5a,b and their hydrazide derivatives 8a,b with cyclic and acyclic glucose gave the condensed S- and N-glycosides 7a,b and 9a,b, respectively. Reaction of 3b with ethyl cyanoacetate followed by reaction with cyclic glucose afforded a mixture of the O- and/or N-glycoside isomers 12 and 13, respectively. The pyrazolo[3,4-c]pyrazole derivative 14 was also obtained from the reaction of 3b with hydrazine hydrate...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28323522/detection-of-cytosine-and-cpg-density-in-proto-oncogenes-and-tumor-suppressor-genes-in-promoter-sequences-of-acute-myeloid-leukemia
#8
Senol Dogan, Anis Cilic, Damir Marjanovic, Amina Kurtovic-Kozaric
Aberrant methylation is one of the driving forces of cancer genome development. Although the rate of methylation appears massively variable across the genome, it is mainly observed in histone modification, chromatin organization, DNA accessibility, or promoter sequence. Methylation of promoter sequence occurs mostly to cytosine nucleotides, which can affect transcription factors' binding affinities. In this study, we demonstrated that cytosine repeats (C types density), consisting of CC, CCC, CCCC, CCCCC, CCCCCC, CCCCCCC motifs and CpG islands density in 25 proto-oncogenes, tumor suppressor genes and control genes may play a role in the pathogenesis of acute myeloid leukemia...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28323520/anti-proliferation-effect-of-guanosine-on-hct-116-cells-involves-mapk-and-ampk-pathways
#9
Wuen Yew Teoh, Norhanom Abdul Wahab, Kae Shin Sim
This study aims to investigate the mechanisms associated with the anti-proliferation effect of guanosine on human colon carcinoma HCT 116 cells. In this study, guanosine induced more drastic cell cycle arrest effect than cell death effect on HCT 116 cells. The cell cycle arrest effect of guanosine on HCT 116 cells appeared to be associated with the increased activation of mitogen-activated protein kinases (MAPK) such as ERK1/2, p38 and JNK. The decreased of AMP-activated protein kinase (AMPK) activation and cyclin D1 expression was also involved...
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28323518/synthesis-crystallization-and-preliminary-crystallographic-analysis-of-a-52-nucleotide-dna-2-ome-rna-oligomer-mimicking-10-23-dnazyme-in-the-complex-with-a-substrate
#10
Rafał Dolot, Milena Sobczak, Barbara Mikołajczyk, Barbara Nawrot
A 52-nucleotide DNA/2'-OMe-RNA oligomer mimicking 10-23 DNAzyme in the complex with its substrate was synthesized, purified and crystallized by the hanging-drop method using 0.8 M sodium potassium tartrate as a precipitant. A data set to 1.21 Å resolution was collected from a monocrystal at 100 K using synchrotron radiation on a beamline BL14.1 at BESSY. The crystal belonged to the P21 group with unit-cell a = 49.42, b = 24.69, c = 50.23, β = 118.48.
March 21, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28282254/synthesis-of-two-fluorescent-gtp%C3%AE-s-molecules-and-their-biological-relevance
#11
Denise J Trans, Ruoli Bai, J Bennet Addison, Ruiwu Liu, Ernest Hamel, Matthew A Coleman, Paul T Henderson
Fluorescent GTP analogues are utilized for an assortment of nucleic acid and protein characterization studies. Non-hydrolysable analogues such as GTPγS offer the advantage of keeping proteins in a GTP-bound conformation due to their resistance to hydrolysis into GDP. Two novel fluorescent GTPγS molecules were developed by linking fluorescein and tetramethylrhodamine to the γ-thiophosphate of GTPγS. Chemical and biological analysis of these two compounds revealed their successful synthesis and ability to bind to the nucleotide-binding site of tubulin...
March 10, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28387634/comparison-of-x-ray-crystal-structures-of-a-tetradecamer-sequence-d-cccgggtacccggg-2-at-1-7%C3%A2-%C3%A3-resolution
#12
S Karthik, A Thirugnanasambandam, P K Mandal, N Gautham
We present here a comparison of three different X-ray crystal structures of DNA tetradecamer sequence d(CCCGGGTACCCGGG)2 all at about 1.7 Å resolution. The sequence was designed as an attempt to form a DNA four-way junction with A-type helical arms. However, in the presence of zinc, magnesium, and in the absence of any metal ion, it does not take up the junction structure, but forms an A-type double helix. This allowed us to study possible conformational changes in the double helix due to the presence of metal ions...
May 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28387606/antimetabolites-design-synthesis-and-cytotoxic-evaluation-of-novel-dihydropyridine-thioglycosides-and-pyridine-thioglycosides
#13
Galal H Elgemeie, Nahed M Fathy, Ayman B Farag, Sheikha A Alkursani
A convenient synthesis of a novel series of dihydropyridine and pyridine thioglycosides was developed. The evaluation of anti-proliferative activity against HepG-2 cell lines (liver carcinoma cell lines) shows that most of the compounds have antitumor activity, especially 5b, 5f, 5j, 5n, 7b, 7f, 7j, 7n, 8b, 8f, and 8j. The results of molecular docking reveal that these compounds have high binding affinity by hydrogen bond formation with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR)...
May 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28362220/design-synthesis-and-in-vitro-anti-hepatocellular-carcinoma-of-novel-thymine-thioglycoside-analogs-as-new-antimetabolic-agents
#14
Galal H Elgemeie, Ayman B Farag
A first reported direct method for preparation of thymine thioglycoside analogs utilizing novel pyrimidine-2(1H)-thiones and α-bromoglucose or α-bromogalactose tetraacetate as starting components is described. The synthetic potential of the method is demonstrated. The evaluation of antiproliferative activity against HepG-2 cell lines (Liver carcinoma cell lines) shows that most of the compounds have high antitumor activities especially 6b, 6e, 11b, and 12b. Moreover, molecular modelings of these compounds reveal that they have high binding affinity through hydrogen bond interaction with the binding pocket of thymidylate synthase dihydrofolate reductase (TS-DHFR)...
May 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28102781/a-neurodevelopmental-disorder-with-a-nonsense-mutation-in-the-ox-2-antigen-domain-of-the-amyloid-precursor-protein-app-gene
#15
Khue Vu Nguyen, Karen Leydiker, Raymond Wang, Jose Abdenur, William L Nyhan
We report a patient, an infant with a neurodevelopmental disorder manifesting intractable complex partial epilepsy, bull's eye maculopathy, microcephaly, bilateral cataracts, truncal hypotonia, and spasticity of all four extremities. Sequencing of genomic DNA revealed mutations in (a) exon 8 (Ox-2 antigen domain) of the amyloid precursor protein (APP) gene: c.1075C>T, p.Arg359(*) (b) exon 8 of the senataxin (SETX) gene: c.4738C>T, p.Arg1580Cys, and (c) exon 2 of the ceroid-lipofuscinosis, neuronal 8 (CLN8) gene: c...
May 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28102767/synthesis-stereochemical-characterization-and-antimicrobial-evaluation-of-a-potentially-nonnephrotoxic-3-c-acethydrazide-puromycin-analog
#16
Josh Carter, Blair A Weaver, Maria A Chiacchio, Amy R Messersmith, Will E Lynch, Brent D Feske, Giuseppe Gumina
Puromycin is a peptidyl nucleoside endowed with significant antibiotic and anticancer properties, but also with an unfortunate nephrotoxic character that has hampered its use as a chemotherapeutic agent. Since hydrolysis of puromycin's amide to puromycin aminonucleoside is the first metabolic step leading to nephrotoxicity, we designed a 3'-C-hydrazide analog where the nitrogen and carbon functionality around the amide carbonyl of puromycin are inverted. The title compound, synthesized in 11 steps from D-xylose, cannot be metabolized to the nephrotoxic aminonucleoside...
March 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28102765/pyrimidine-non-nucleoside-analogs-a-direct-synthesis-of-a-novel-class-of-n-substituted-amino-and-n-sulfonamide-derivatives-of-pyrimidines
#17
Galal H Elgemeie, Ali M Salah, Nermeen S Abbas, Hoda A Hussein, Reham A Mohamed
A convenient method for the regioselective synthesis of pyrimidine non-nucleoside analogs was developed. This study reports a novel and efficient method for the synthesis of a new type of N-substituted amino methylsulfanylpyrimidines and the corresponding pyrazolo[3,4-d]pyrimidines. This series of compounds was designed through the reaction of dimethyl N-cyanodithioiminocarbonate with 2-cyano-N'-(thiophen-2-yl-, furan-2-yl- and pyridin-4-ylmethylene)acetohydrazide and N'-(2-cyanoacetyl)arylsulfonohydrazides...
March 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28045617/evaluation-of-functional-rage-gene-polymorphisms-in-childhood-acute-lymphoblastic-leukemia-a-case-control-study-from-iran
#18
Ebrahim Eskandari-Nasab, Mohammad Hashemi, Seyed-Shahab-Adin Hasani, Majid Naderi, Simin Sadeghi-Bojd, Mohsen Taheri
We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0...
March 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28045605/new-n-substituted-hydrazones-derivatives-of-uridyl-aldehyde
#19
Katarzyna Kral, Tadeusz Bieg, Agnieszka Kudelko, Anna Barabaś, Aleksandra Dąbrowska, Ilona Wandzik
N-substituted isomeric hydrazones of uridyl aldehyde have been synthesized. The occurrence of the dominant E isomers with respect to the azomethine group was confirmed by means of NMR spectroscopy. Synthesized hydrazones feature an acetonide moiety as a protection of two hydroxyl groups on the ribose part. The attempt to remove the protecting group resulted in an azo-hydrazone tautomeric mixture. The described compounds may be valuable chiral ligands for metal chelation. Assessment of manganese(II) ion affinity to one selected hydrazone was performed...
March 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
https://www.readbyqxmd.com/read/28045593/synthesis-and-antibacterial-activity-of-5-tetrachlorophthalimido-and-5-azido-5-deoxyribonucleosides
#20
Robert Van Ostrand, Casey Jacobsen, Alicia Delahunty, Carley Stringer, Ryan Noorbehesht, Haidi Ahmed, Ahmed M Awad
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...
March 4, 2017: Nucleosides, Nucleotides & Nucleic Acids
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