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1.
Tsuguhisa Kaneko∗ † Hiroshi Yamamoto 《Nucleosides, nucleotides & nucleic acids》2013,32(12):2111-2122
Abstract A previously undescribed pyrimidine ribonucleoside kinase that preferentially phosphorylates cytidine to yield its 5′-monophosphate form has been purified to near homogeneity from Escherichia coli.The enzyme was distinct from the known pyrimidine nucleoside kinase in the chromatographic profile, substrate specificity and molecular weight. 相似文献
2.
Nucleic acid research frequently necessitates the analytical resolution of nucleic acid derivatives. Thin-layer chromatography (tlc), for its simplicity, short development time, and superior resolving power, is often preferable to other methods (1–3). Although the literature contains a large number of methods that have been devised for the separation of purine and pyrimidine derivatives (4,5) no tlc technique has hitherto been described for the concomitant separation of bases, nucleosides, nucleoside 5′-monophosphates, nucleoside 3′-monophosphates, nucleoside diphosphates, and nucleoside triphosphates.The present communication deals with methods devised for the simultaneous separation of the above-mentioned pyrimidine derivatives. They enable the resolution of either the six uracil derivatives or the six cytosine derivatives, on commercial cellulose tlc sheets. Alternatively, the six pyrimidine derivatives can be separated on cellulose layers 0.75 mm thick. Since formic acid extracts of bacterial cells do not interfere with the separation, these methods can be used for the direct estimation of extracts of biological materials. 相似文献
3.
Reza Fathi Kenneth J. Nawoschik Melissa Zavoda Alan F. Cook 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1907-1920
Abstract A wide range of 2′,5′-dideoxy-nucleosides, including 6- substituted purine, pyrazolo[3,4-d]pyrimidine and 1-deazapurine derivatives, has been enzymatically prepared using purine nucleoside phosphorylase. Specificity towards cleavage by bacterial versus mammalian purine nucleoside phosphorylase was evaluated. 相似文献
4.
Abstract A procedure was developed for the chemical synthesis of P1,P2-dinucleoside-5′-diphosphates (N1(5′)pp(5′)N2) on a nanomolar scale Reaction conditions for activating purine-5′-monophosphates (pA, pG, and pm7G) by 1,1′-carbonyldiimidazole were studied and optimized in respect to solvents and amount of activating reagent used. Various dinucleoside-5′-diphosphates were synthesized in 62-98% yield by incubating activated and non-activated purine-5′-monophosphates. Two unexpected by-products were formed by competition reactions: the imidazolidate of the non-activated nucleotide and the corresponding symmetrically substituted dinucleoside-5′-diphosphate. A mechanism is proposed to explain the observed side reactions. 相似文献
5.
Prakash C. Joshi Michael F. Aldersley Dmitri V. Zagorevskii James P. Ferris 《Nucleosides, nucleotides & nucleic acids》2013,32(7):536-566
A synthesis has been developed providing nucleotide dimers comprising natural or unnatural nucleoside residues. A ribonucleoside 5′-phosphorimidazolide is added to a nucleoside adsorbed on montmorillonite at neutral pH with the absence of protecting groups. Approximately 30% of the imidazolide is converted into each 2′-5′ dimer and 3′-5′ dimer with the rest hydrolyzed to the 5′-monophosphate. Experiments with many combinations have suggested the limits to which this method may be applied, including heterochiral and chimeric syntheses. This greener chemistry has enabled the synthesis of dimers from activated nucleotides themselves, activated nucleotides with nucleosides, and activated nucleotides with nucleotide 5′-monophosphates. [Supplemental materials are available for this article. Go to the publisher's online edition of Nucleosides, Nucleotides & Nucleic Acids to view the free supplemental files.] 相似文献
6.
《Biochimica et Biophysica Acta (BBA)/General Subjects》2017,1861(3):603-614
Nucleotide pyrophosphatase/phosphodiesterase 1 (NPP1) represents the main subtype of the NPP family of nucleotide hydrolyzing enzymes. The ecto-enzyme hydrolyzes structurally diverse substrates and has recently been proposed as a drug target for immuno-oncology. To get more insights into the nature of the promiscuity of NPP1, we investigated its substrate preferences employing a broad range of natural nucleotides including ATP, UTP, diadenosine tetraphosphate (AP4A), cAMP, and cyclic guanosine-(2′,5′)-monophosphate-adenosine-(3″,5″)-monophosphate (2′,3″-cGAMP), as well as the artificial substrate p-nitrophenyl 5′-thymidine monophosphate (p-Nph-5′-TMP). Despite their diverse structures, all substrates were converted to nucleoside 5′-monophosphates; 2′,3″-cGAMP yielded exclusively the nucleoside 5′-monophosphates AMP and GMP. In contrast, 3′,3″-bridged cyclic dinucleotides were not hydrolyzed. ATP was the most efficiently hydrolyzed substrate of NPP1, followed by AP4A and 2′,3″-cGAMP. UTP, cAMP and p-Nph-5′-TMP were much poorer substrates. A homology model of the human NPP1 was built based on the X-ray structure of its mouse orthologue. Docking studies were performed based on previously published mutagenesis data to rationalize the interactions of the different substrates and to explain the enzyme's preferences. The results provide an improved understanding of the interactions of NPP1 with its diverse substrates and will contribute to the validation of NPP1 as a drug target. 相似文献
7.
Weidong Hu Qinghua Yang Shuyang Wang Gang Huang Yueteng Zhang Jingjing Dong 《Nucleosides, nucleotides & nucleic acids》2013,32(7):389-395
A new route for the synthesis of the anti-HCV nucleoside analogue, 4-amino-5-fluoro-7-(2′-deoxy-2′-fluoro-2′-C-methyl-β-d-ribofuranosyl)-1H-pyrrolo[2,3-d]pyrimidine 1, was developed. 相似文献
8.
Magnus Björsne Björn Classon Inger Kers Bertil Samuelsson Ingemar Kvarnström 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):283-286
Abstract Some 2′,3′-dideoxy-3′, 4′-dihydroxymethyl nucleoside analogues have been synthesised starting from diacetone-D-glucose. The 3-C-hydroxymethyl group was introduced by selective hydroboration-oxidation of the 3-C-methylene derivative. The 4-C-hydroxymethyl group was obtained by an aldol condensation followed by in situ cross Canizzaro reduction. Glycosylation using silylated pyrimidine bases furnished the 2′,3′-dideoxy-3′,4′-dihydroxymethyl nucleoside analogues. 相似文献
9.
Kôichi Ogata Akira Imada Yoshio Nakao 《Bioscience, biotechnology, and biochemistry》2013,77(9):586-623
A Bacillus accumulated 5′-nucleotides in the culture fluid during cultivation. These nucleotides consisted mainly of ribonucleoside 5′-monophosphates and of traces of nucleoside 5′-diphosphates. The composition of the accumulated nucleotides resembled that of the nucleotides of intracellular RNA. Therefore an intimate relationship between the accumulation of nucleotides and the metabolism of endogenous RNA was suggested.The excretion of 5′-nucleotides into the culture fluid took place in parallel with the reduction of intracellular RNA, and it was presumed that the accumulated nucleotides were products of degradation of intracellular RNA. 相似文献
10.
Mallela S.P. Sarma Marianne R. Spada Sreenivasulu Megati Robert S. Klein Brian A. Otter 《Nucleosides, nucleotides & nucleic acids》2013,32(10-11):1983-1998
Abstract Two approaches to the synthesis of the title compounds are described. In the first route, a reactive 5-oxo-6-methylene pyrimidine intermediate that is generated by treating the bis-acetylated or bis-benzoylated nucleosides 10 and 11 with sodium hydroxide undergoes intramolecular attack by the 5′-thiol group to afford the 5-hydroxy cyclonucleoside 12. In the second and higher yielding approach, the S5′,6-methano linkage is established by an internal allylic displacement reaction that occurs when the 5-bromo-6-methyl nucleoside 24 is treated with base. The conformational properties of S5′,6-methano-5′-thiouridine (3) and certain long-range spin-spin couplings observed in the NMR spectra of the intermediate nucleosides are discussed. 相似文献
11.
T. Ton-That 《Nucleosides, nucleotides & nucleic acids》2013,32(4-5):731-732
Abstract The synthesis of some new 3′-azido-3′-C-substituted pyrimidine nucleoside analogues is described. The key step is the geminal disubstitution of an appropriated ketone carbohydrate, via the regioselective ring opening of the corresponding tosyl-epoxide derivative. 相似文献
12.
Joanna Romanowska Agnieszka Szymańska-Michalak Jerzy Boryski Jacek Stawiński Adam Kraszewski Roberta Loddo Giuseppina Sanna Gabriella Collu Barbara Secci Paolo La Colla 《Bioorganic & medicinal chemistry》2009,17(9):3489-3498
Di-aryl nucleoside phosphotriesters have been explored as a new type of pronucleotides for the purpose of anti-HIV-1 therapy and efficient synthetic protocols, based on H-phosphonate chemistry, have been developed for the preparation of this class of compounds. It was found that anti-HIV-1 activity of the phosphotriesters bearing an antiviral nucleoside moiety (AZT, ddA) and also ddU was due, at least partially, to intracellular conversion into the corresponding nucleoside 5′-monophosphates, and their efficiency correlated well with the pKa values of the aryloxy groups present. 相似文献
13.
M. Berger A. Shaw J. Cadet J. R. Jones 《Nucleosides, nucleotides & nucleic acids》2013,32(1-2):395-396
Abstract The deuterations of 2′-deoxyguanosine in the 4′ and 5′ positions have been described elsewhere (1). The starting material is the 5′-aldehyde formed by mild oxidation with N,N-dicyclohexyl carbodiimide in dimethyl sulphoxide of the fully protected nucleoside with free 5′-alcoholic function. The 5′4euteration was achieved by reduction with deuterated sodium borohydride. Incorporation of deuterium in the 4′-position was achieved v i a an enhanced keto-enol tautomerim by heating the aldehyde in 50/50 D20/pyridine, with subsequent reduction of the aldehyde with NaBH4. The 6-furanoid form was isolated from the I-lyxo by-product by reverse phase HPLC. Applied to pyrimidine 2′-deoxyribonucleosides, this method was shown to give deuterated 2′-deoxycytidine and thymidine in good yield. 相似文献
14.
Abstract 5-Methyl-2′-deoxycytidine 5′-[32P]- and deoxycytidine 5-[32 P]-monophosphates were prepared from corresponding nucleotide homopolymers by using a 32 P-postlabeling procedure. The radioactive monophosphates obtained were well suited for biological and biochemical experiments. 相似文献
15.
Srinivas Gadthula Chung K. Chu Raymond F. Schinazi 《Nucleosides, nucleotides & nucleic acids》2013,32(10-12):1707-1727
Since the discovery of 3′-azido-3′-deoxythymidine (AZT) and 2′,3′-didehydro-2′,3′-dideoxythymidine (d4T) as potent and selective inhibitors of the replication of human immunodeficiency virus (HIV), there has been a growing interest for the synthesis of 2′,3′-didehydro-2′,3′-dideoxynucleosides with electron withdrawing groups on the sugar moiety. Here we described an efficient method for the synthesis of such nucleoside analogs bearing structural features of both AZT and d4T. The key intermediate, 3-azido-1,2-bis-O-acetyl-5-O-benzoyl-3-deoxy-D-ribofuranose, 5 was synthesized from commercially available D-xylose in five steps, from which a series of pyrimidine and purine nucleosides were synthesized in high yields. The resultant protected nucleosides were converted to target nucleosides using appropriate chemical modifications. The final nucleosides were evaluated as potential anti-HIV agents. 相似文献
16.
Adenosine kinase catalyses ribonucleoside-5′-monophosphate synthesis from various N6-substituted analogues of adenosine. The nature of the N6-substituent sharply influences the rate of the synthesis with enzymes from different plant systems. Attempts to synthesize nucleoside triphosphates from several purified N6-substituted adenosine-5′-monophosphates using a number of different enzyme systems, were not successful. The significance of the results to our understanding of the in vivo metabolism of cytokinin is discussed. 相似文献
17.
Magnus Björsne Tomas Szabó Bertil Samuelsson Björn Classon 《Nucleosides, nucleotides & nucleic acids》2013,32(3-5):279-282
Abstract In order to obtain a high degree of rigidity within the sugar moiety of nucleosides, some bicyclic pyrimidine nucleoside analogues where synthesized starting from cyclopentanone. The C-4′-substituent is fused to the C-3′-position via a propylene to give a [3.3.0]-bicyclic ring system. 相似文献
18.
Norbert Bischofberger Mark D. Matteucci 《Nucleosides, nucleotides & nucleic acids》2013,32(5-6):859-862
Abstract We have synthesized polycyclic nucleoside derivatives by a novel, one pot procedure by reacting 4-0-TPS-pyrimidine nucleosides with aromatic diamines. The reaction is limited in scope but provides easy access to certain previously unknown heterocyclic ring systems.2 4-0-Triisopro- pylphenylsulfonyl-pyrimidine nucleosides were reacted with aromatic diamines leading to fused, polycyclic ring systems: o-phenylenediamine yielded the pyrimido[1,6-a]benzimidazole, 2.3- diaminonaphthalene gave the naphth[2′,3′:4,5]imidam [1.2-flpyrimidine and 1.8-diaminonaph- thalene led to the pyrimido[l,6-a]perimidine ring system. The reaction is unique because two connected nucleophilic centers react with the pyrimidine nucleoside to form an extended ring system. However, reactions of pyrimidine nucleosides with electrophiles are well known. E.g., reaction of cytidine and adenosine with bromoacetaldehyde yields ethenocytidine and ethenoadenosine) and on reaction of cytidine with 1′-methylthiaminium salts dipyrimido[1,6-a:4′,5′-d]pyrimidine derivatives are obtained.4 Other polycyclic bases have been made from cytidine and adenosine by photochemical reactions5. 相似文献
19.
Abstract The applicability of HPLC as a method to study the kinetics of complicated reaction systems of nucleosides and nucleotides has been demonstrated by using the hydrolytic reactions of cytidine 2′- and 3′-monophosphates as an example. 相似文献
20.
Anne Routledge Ian Walker Sally Freeman Alan Hay Naheed Mahmood 《Nucleosides, nucleotides & nucleic acids》2013,32(7):1545-1558
Abstract 4-Acyloxybenzyl bis(nucleosid-5′-yl) phosphates 7a-c and 9a-c were prepared as potential prodrugs of the anti-HIV nucleosides 3′-azido-3′-deoxythymidine (AZT) and 2′,3′-dideoxyinosine (ddI) or their 5′-monophosphates. The anti-HIV activities of these triesters were determined in two T-cell lines. In a C8166 cell line they displayed activities comparable to and in some cases superior to AZT, but they also exhibited an increase in cytotoxicity. In a thymidine kinase deficient JM T-cell line the activity was reduced but was still superior to AZT. In the presence of porcine liver carboxyesterase (PLCE), triester 7b biodegrades to the diester 10 which, with phosphodiesterase, gives initially AZT monophosphate 3 and AZT. 相似文献