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Topic: Nucleoside

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In the News (Wed 21 Aug 19)

  Nucleoside - Wikipedia, the free encyclopedia
Nucleosides are glycosylamines made by attaching a nucleobase (often referred to simply as bases) to a ribose or deoxyribose ring.
Nucleosides can be phosphorylated by specific kinases in the cell, producing nucleotides, which are the molecular building blocks of DNA and RNA.
Nucleosides are produced as the second step in nucleic acid digestion, when nucleotidases break down nucleotides (such as the thymine nucleotide) into nucleosides (such as thymidine) and phosphate.
en.wikipedia.org /wiki/Nucleoside   (202 words)

 Idenix Pharmaceuticals: Nucleosides & Nucleoside Analogs   (Site not responding. Last check: 2007-10-10)
Nucleosides are small, natural chemical compounds that function as the building blocks of human and viral genetic material, commonly referred to as DNA and RNA.
Naturally occurring nucleosides are modified in cells to generate derivatives, termed nucleotides, that are utilized by polymerases as the basic building blocks of DNA and RNA genetic material.
The benefits of nucleosides and nucleoside analogs are borne out by a proven track record of scientific, development and commercial success as antiviral treatments for hepatitis B, hepatitis C and HIV.
www.idenix.com /science/sci_nucleosides.html   (243 words)

 Nucleoside Analogs
All four of these drugs and other nucleoside analogs are believed to have a similar mechanism of HIV inhibition, in which the nucleosides are progressively phosphorylated to a 5'-triphosphate, which then acts as a chain terminator in a reverse transcriptase (RT) reaction.
HIV viral isolates from patients are often resistant to the nucleoside analog that was used therapeutically in the patient.
Nucleoside analogs will continue to play a major role in anti-HIV therapy, current efforts are underway to develop analogs that are less toxic, less susceptible to viral resistance and less dependent on kinases whose activity varies from cell to cell.
www.niaid.nih.gov /daids/dtpdb/nucana.asp   (798 words)

 Pharmacokinetic Properties of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors
Nucleoside and nucleotide analogues are prodrugs that must be metabolized intracellularly to phosphorylated compounds to exert their activity.
The intracellular concentration of nucleoside analogue triphosphates is regulated by positive or negative feedback mechanisms on >=1 enzymes in the phosphorylation pathway.
The kinetics of thymidine nucleoside analogue phosphorylation are somewhat dependent on the cell cycle, at least in stimulated lymphocytes.
www.natap.org /2004/HIV/082304_02.htm   (5587 words)

 Incorporation of Nucleoside Analogs into Nuclear or Mitochondrial DNA Is Determined by the Intracellular ...   (Site not responding. Last check: 2007-10-10)
nucleoside analogs phosphorylated in the mitochondria induce apoptosis,
Induction of apoptosis by the nucleoside analog CdA.
that nucleoside analogs phosphorylated by the mitochondrial nucleoside
www.jbc.org /cgi/content/full/275/35/26727   (2676 words)

 [No title]
These artificial nucleosides are slightly different in composition and properties from the natural molecules.
Nucleoside analogues are taken in by the virus and used to form the reproductive enzyme reverse transcriptase.
But the enzyme built with these "false" nucleosides will not perform correctly, and the virus is therefore unable to complete its reproductive cycle.
www.critpath.org /aric/gloss/body/nucleoside_analogue.htm   (590 words)

 Functional Differences in Nucleoside and Nucleobase Transporters Expressed on the Rabbit Corneal Epithelial Cell Line ...
Nucleoside and nucleobase transporters on rabbit cornea and corneal epithelial cell line, SIRC, are functionally different, undermining the utility of the SIRC cell line as an in vitro screening tool for elucidating the corneal permeation mechanism of nucleoside analogs.
Nucleoside transporters are classified into 2 categories based on their sodium dependency: sodium-independent equilibrative nucleoside transporters (facilitated diffusion) and concentrative (sodium dependent) nucleoside transporters.
Nucleoside analogs targeted toward the nucleoside transporter expressed on the cornea represent an exciting and clinically relevant strategy to enhance drug concentrations in the deeper corneal layers as well as in the anterior chamber of the eye.
www.aapsj.org /view.asp?art=ps050215   (4343 words)

 Nucleoside - EvoWiki   (Site not responding. Last check: 2007-10-10)
A nucleoside is a nucleic acid base (adenine, thymine, guanine, cytosine, or uracil) covalently bonded to either ribose or deoxyribose.
Nucleoside monophosphates join together by phosphodiester bonds (ie C-O-P-O-C) to form single-stranded DNA and RNA; these can then form either double stranded nucleic acids or DNA-RNA hybrids by hydrogen bonding between the bases.
It is the primary energy currency of the cell; energy used to drive thermodynamically unfavourable biochemical reactions is obtained by cleaving the phosphoryl group from the end, creating ADP and orthophosphate.
wiki.cotch.net /index.php/Nucleoside   (213 words)

 Nucleoside derivatives and an antileukemial agent containing the same as an active ingredient - Patent 4297347
A 3'-polyphosphate of pyrimidine nucleoside or guanosine or a pharmaceutically acceptable salt thereof which has high antileukemial activity and is low in toxicity is disclosed.
Nucleosides occur in all living cells as a component of nucleic acid, and the nucleotide which is the class of esters formed by interacting nucleosides with phosphoric acid has been the subject of many studies conducted to date, but adenosine has been the only nucleoside from which 3'-polyphosphates (e.g.
The inventors of this invention have succeeded in preparing a novel nucleoside-3'-polyphosphate by first converting 3'-monophosphate of pyrimidine nucleoside or guanosine to the corresponding reactive derivative such as amidate or morpholidate in the conventional manner and esterifying the derivative with phosphoric acid.
www.freepatentsonline.com /4297347.html   (2422 words)

 SF AIDS Fdn: BETA Summer 2000 -- The Wide-Ranging Effects Of Nucleoside Analogs
Natural nucleosides are first phosphorylated (chemically reconfigured) into nucleotides and then chained together to form DNA; this is done by both reverse transcriptase and the cells' own enzymes during gene replication.
Obesity and prolonged nucleoside exposure may be risk factors." This hepatic degeneration resembles "acute fatty liver" of pregnancy, a maternal syndrome that threatens both mother and fetus and results from an inherited fetal inability to oxidize fatty acids in the mitochondria.
Parker, W.B. and Cheng, Y.C. Mitochondrial toxicity of antiviral nucleoside analogs.
www.sfaf.org /treatment/beta/b44/b44toxicity.html   (4710 words)

 (ATN) 1993 Nucleoside-Analog Trial Results Expected
Nucleoside analogs are often discounted by people who argue, incontestably, that there are stringent limits to what these drugs can do and that their various side effects often cause great problems to patients.
That may be true, but there is a fairly clear understanding of how they work and how their side effects can sometimes be managed; three are FDA-approved and two more may be on the way to approval; and they are backed by big drug companies with the resources to develop them quickly.
Although nucleosides are of limited efficacy, those limits may not turn out to be so stringent as was once thought, if up to five drugs come to be used serially and in combinations.
www.aegis.com /pubs/atn/1993/ATN16602.html   (1262 words)

 Adverse Effects with Nucleoside Analogs (’Nukes’)
Nucleoside analogs interfere with DNA synthesis, about the most dangerous thing that a drug can do.
There was a marked decrease in complex IV activity in muscle biopsies from four of five patients, consistent with a mitochondrial dysfunction...One patient developed severe lactic acidosis...and died.
Among the remaining 12 patients, nucleoside analogue therapy was stopped in 10, as clinical improvement was combined with a decrease in lactate levels...The improvements observed in the next few weeks after drug withdrawal or modification suggest that antiretroviral drugs are responsible for the occurrence of symptomatic hyperlactataemia.
www.aras.ab.ca /haart-nukes.html   (1376 words)

 Nucleoside Reverse Transcriptase Inhibitors (NRTIs) for HIV & AIDS   (Site not responding. Last check: 2007-10-10)
NRTIs, sometimes referred to as "Nucleoside Analogues" – or "nukes" for short – prevent healthy T-cells in the body from becoming infected with HIV.
In turn, HIV's genetic material cannot be incorporated into the healthy genetic material of the cell and prevents the cell from producing new virus.
In order for nucleoside analogues to work, they must undergo chemical changes (phosphorylation) to become active in the body.
www.aidsmeds.com /NRTIs.htm   (349 words)

 (ATDN) Drug Glossary
Nucleosides are one of the building blocks of DNA, and DNA stores information necessary for creating any new living thing.
Nucleoside analogs like AZT get into cells in the body and are mixed up with the virus' DNA as the virus tries to infect those cells.
Nucleoside analogs may also sometimes inhibit production of human DNA in healthy cells, causing side effects.
www.aegis.com /pubs/atdn/1996/ATR02316.html   (1022 words)

 Pentose phosphates in nucleoside interconversion and catabolism -- Tozzi et al. 273 (6): 1089 -- FEBS Journal   (Site not responding. Last check: 2007-10-10)
Nucleosides enter the cell through specific transporters and are ultimately subjected to a phosphorolytic cleavage, catalysed by nucleoside phosphorylases (enzyme 1).
Barsotti C, Pesi R, Felice F and Ipata PL (2003) The purine nucleoside cycle in cell-free extracs of rat brain: evidence for the occurrence of an inosine and a guanosine cycle with distinct metabolic roles.
In Metabolism of Nucleotides, Nucleosides and Nucleobases in Microorganisms (Munch-Petersen A, ed.), pp.
content.febsjournal.org /cgi/content/full/273/6/1089   (6596 words)

 SwoHp, a Nucleoside Diphosphate Kinase, Is Essential in Aspergillus nidulans -- Lin et al. 2 (6): 1169 -- Eukaryotic ...
Adenylate kinase complements nucleoside diphosphate kinase deficiency in nucleotide metabolism.
Nucleoside diphosphate kinase beta (Nm23-R1/NDPKß) is associated with intermediate filaments and becomes upregulated upon cAMP-induced differentiation of rat C6 glioma.
Purification and characterization of nucleoside diphosphate kinase from the brain of Bombyx mori.
ec.asm.org /cgi/content/full/2/6/1169   (6137 words)

 Characterization of nucleoside transport systems in cultured rat epididymal epithelium -- Leung et al. 280 (5): C1076 ...
nucleoside transporter 2 (CNT2) and the latter is CNT1 (11,
Identification of nucleoside transporters in proximal and distal regions of rat epididymis by RT-PCR.
Concentrative transport of purine nucleosides in brush border vesicles of the rat kidney.
ajpcell.physiology.org /cgi/content/full/280/5/C1076   (4081 words)

 Nucleoside-sparing regimens
The increasing link between nucleoside analogues and lipoatrophy and increased potency of ritonavir-boosted protease inhibitors have led to a number of so-called nucleoside sparing strategies, both in treatment naïve and experienced patients.
The results are remarkable, and compartmental penetration is considered within the study, but a patient advantage apart from reduced drug use is not clear, as tolerability of boosted PI regimens is largely related to the boosted-PI component of the therapy.
At baseline nucleosides were stopped and patients monitored at week two and then monthly for viral load (LQ=20 copies/ml), CD4, and activation markers (CD38 and HLA-DR), and at baseline and week 48 with DEXA.
www.i-base.org.uk /pub/htb/v4/htb4-7/Nucleoside.html   (1755 words)

 Lipid-mediated Protein Delivery of Suicide Nucleoside Kinases -- Zheng et al. 63 (20): 6909 -- Cancer Research
Nucleoside kinase activity in cells incubated with the lipid enzyme complexes.
Sensitivity of osteosarcoma cells to the nucleoside analogues GCV, BVDU, or araT incubated with either HSV-1 TK (A) or Dm-dNK (B).
Degreve B., De Clercq E., Balzarini J. Bystander effect of purine nucleoside analogues in HSV-1 tk suicide gene therapy is superior to that of pyrimidine nucleoside analogues.
cancerres.aacrjournals.org /cgi/content/full/63/20/6909   (2899 words)

 Localization of GFP-tagged concentrative nucleoside transporters in a renal polarized epithelial cell line -- ...
To determine the uptake of nucleosides across the apical or basolateral membrane, the following procedure was used.
and uridine is transported by all subtypes of nucleoside transporters.
Characterization of Na(+)-dependent, active nucleoside transport in rat and mouse peritoneal macrophages, a mouse macrophage cell line and normal rat kidney cells.
ajprenal.physiology.org /cgi/content/full/280/5/F879   (3940 words)

 Alibris: Nucleosides
Offering the most current and complete coverage of nucleoside analog activity in oncology and hematology, this single-source volume includes topics from pharmacology to previously unpublished clinical findings on the pivotal role of fludarabine, cladribine, and pentostatin in the management of diseases, such as chronic lymphocytic and hairy cell...
Metabolism of nucleotides, nucleosides and nucleobases in microorganisms
Modified nucleosides of transfer RNA : A bibliography of biochemical and biophysical studies from 1970 to 1979.
www.alibris.com /search/books/subject/Nucleosides   (550 words)

Abstract: Nucleoside analogs have been clearly demonstrated to be effective in the treatment of a variety of hematologic malignancies and several have promise for the treatment of solid tumors and retroviral infections.
This proposal seeks to elucidate at a basic genetic level factors controlling the expression of several enzymes that are critical to the activation of a number of clinically useful nucleoside analogs.
The cytoplasmic or soluble 5'- nucleotidase that has been implicated in the phosphorolysis of purine nucleoside analogs, as well as in the inverse phosphorylation of several dideoxynucleosides useful in AIDS treatment, will be purified and the corresponding cDNA cloned.
www.med.unc.edu /wrkunits/1dean/research/Mitchell265.html   (514 words)

 Antiretrovirals: Nucleoside Analog and Non-Nucleoside Reverse Transcriptase Inhibitors
While most of the public attention has been focused on protease inhibitors, the preponderance of available data suggests that combinations of the currently marketed products are probably more effective than the sequential monotherapy that had been the standard treatment for HIV infection.
The nucleoside analog reverse transcriptase inhibitors were the first antiretroviral agents used to treat HIV-1 infection.
While no treatment regimen has been shown to be clinically superior to ddI, most researchers agree that the superior magnitude and duration of virologic effects using combination therapies outweigh the relative ease of administration and lower cost of ddI monotherapy.
www.hivpositive.com /f-Topics/f-RetroviralConf/Nucleoside.html   (3371 words)

 Combination of nucleoside analogues in the treatment of chronic hepatitis B virus infection: lesson from experimental ...
Combination of nucleoside analogues in the treatment of chronic hepatitis B virus infection: lesson from experimental models
Zoulim, F. Mechanism of viral persistence and resistance to nucleoside and nucleotide analogs in chronic hepatitis B virus infection.
Combinations of adefovir with nucleoside analogs produce additive antiviral effects against hepatitis B virus in vitro.
jac.oxfordjournals.org /cgi/content/full/55/5/608   (2401 words)

 Specificity of human and rat orthologs of the concentrative nucleoside transporter, SPNT -- Gerstin et al. 283 (2): 344 ...
Several ribose-modified nucleoside analogs were studied to determine whether modifications to the ribose were tolerated (Fig.
Sequence of a pyrimidine-selective Na /nucleoside cotransporter from pig kidney, pkCNT1.
Structure-inhibitory profiles of nucleosides for the human intestinal N1 and N2 Na -nucleoside transporters.
ajprenal.physiology.org /cgi/content/full/283/2/F344   (3321 words)

 InterPro: IPR001910 Inosine/uridine-preferring nucleoside hydrolase   (Site not responding. Last check: 2007-10-10)
Inosine-uridine preferring nucleoside hydrolase (EC: (IU-nucleoside hydrolase or IUNH) is an enzyme first identified in protozoan [ 1 ] that catalyzes the hydrolysis of all of the commonly occuring purine and pyrimidine nucleosides into ribose and the associated base, but has a preference for inosine and uridine as substrates.
IUNH from Crithidia fasciculata has been sequenced and characterized, it is an homotetrameric enzyme of subunits of 34 Kd.
Giabbai B. Degano M. Crystal structure to 1.7 a of the Escherichia coli pyrimidine nucleoside hydrolase YeiK, a novel candidate for cancer gene therapy.
www.ebi.ac.uk /interpro/IEntry?ac=IPR001910   (3132 words)

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