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HIV Report September 1997 - Product Information Conversion of AZT to the monophosphate form is highly efficient, but conversion of AZT monophosphate to the triphosphate form appears to occur with less than 1% of the efficiency of the conversion of thymidine monophosphate to thymidine triphosphate. AZT and thymidine are phosphorylated to the monophosphate form by thymidine kinase and then to the triphosphate form by thymidylate kinase. AZT triphosphate inhibits HIV reverse transcriptase by competing with endogenous thymidine triphosphate. www.hopkins-aids.edu /publications/report/sep97_10.html.1

Human immunodeficiency virus reverse transcriptase. General properties and its interactions with nucleoside triphosphate analogs. This study provides information on the structure activity relationships of the triphosphate analogs inhibitory effects on HIV reverse transcriptase versus human gamma-polymerase-associated reverse transcriptase, and the possible mechanisms of action of 3' azido thymidine and the 2',3'-dideoxynucleosides, and also identifies other nucleoside analogs for possible development as inhibitors of HIV. The Ki values for thymidine triphosphate analogs with HIV reverse transcriptase ranged from 5 to 13 nM with decreasing effectiveness for 3'-fluoro greater than 3'-amino greater than 2',3'-dideoxy greater than 3'-azido groups. The preferential inhibition of HIV reverse transcriptase as compared to human gamma-reverse transcriptase was observed with several nucleoside analog triphosphates. www.aegis.com /aidsline/1987/jun/M8760190.html   (408 words)

1997, sci.med.aids thread - FLT & Too Much TP The levels of nucleoside analog triphosphate shown here [Table 1] correlate directly with the cytotoxicities of these analogs measured previously in CEM cells and suggest that the relatively high cytotoxicity of FLT may be due to its anabolism with an efficiency apparently indistinguishable from that of thymidine. They state "The levels of nucleoside analog triphosphate shown here [Table 1] correlate directly with the cytotoxicities of these analogs measured previously in CEM cells and suggest that the relatively high cytotoxicity of FLT may be due to its anabolism with an efficiency apparently indistinguishable from that of thymidine." Page 334: The mechanism of anti-human immunodeficiency virus activity of nucleoside analogs requires that host kinases phosphorylate the nucleoside substrate to the corresponding nucleoside mono-, di-, and triphosphates, and it is the triphosphate which is usually responsible for the antiviral activity. www.hsph.harvard.edu /Organizations/healthnet/HIV/docs/scimed02/SciMed01540.html   (488 words)

Deoxyribonucleoside Triphosphate Pool Imbalances In Vivo Are Associated with an Increased Retroviral Mutation Rate -- Julias and Pathak 72 (10): 7941 -- The Journal of Virology D17 target cells for infection were treated with HU or thymidine for 4 h and then infected with virus for 1 h. The same assay was used to determine the effects of thymidine on the SNV mutant frequencies. Thymidine treatment had a similar effect on the MLV mutant frequency. jvi.asm.org /cgi/content/full/72/10/7941   (6868 words)

Different Roles for Nonhomologous End Joining and Homologous Recombination following Replication Arrest in Mammalian Cells -- Lundin et al. 22 (16): 5869 -- Molecular and Cellular Biology Effects of thymidine on deoxyribonucleoside triphosphate pools and deoxyribonucleic acid synthesis in Chinese hamster ovary cells. HR is potently induced in the hprt gene by treatment of Chinese hamster cell lines with either hydroxyurea or thymidine. Arrest of DNA replication by thymidine or hydroxyurea generates substrates for recombination. mcb.asm.org /cgi/content/full/22/16/5869   (6635 words)

Thymidine kinase - Wikipedia, the free encyclopedia Thymidine kinase catalyses the reaction: Thd + ATP= TMP + ADP, where Thd is deoxythymidine, ATP is (energy rich) adenosine 5’-triphosphate, TMP is deoxythymidine 5’-phosphate and ADP is adenosine 5’-diphosphate. The first indirect use of thymidine kinase in biochemical research was the identification of dividing cells by incorporation of radiolabeled thymidine and subsequent measurement of the radioactivity or autoradiography to identify the dividing cells. Thymidine kinase I is such a salvage enzyme while thymidine kinase II is not cell cycle dependent. en.wikipedia.org /wiki/Thymidine_kinase   (2005 words)

THYMIDINE (PYRIMIDINE NUCLEOSIDE) When N1 is linked to the C1 of ribose, thymine forms a pyrimidine nucleoside called thymidines which are phosphorylated with from one to three phosphoric acid groups to form the three nucleotides; thymidine monophosphate(TMP), thymidine diphosphate(TDP), and thymidine triphosphate (TTP) respectively. Deoxythymidine Monophosphate (dTMP), a nucleotide, the 5'-phosphate of deoxythymidine. Thymidine is significant because of its involvement in the biosynthesis of DNA and in the preservation and transfer of genetic information. www.chemicalland21.com /arokorhi/lifescience/phar/THYMIDINE.htm   (2005 words)

Modulation of the phosphorylation of 3'-azidothymidine by the human thymidine kinase by 5'-aminothymidine and thymidine triphosphate. Modulation of the phosphorylation of 3'-azidothymidine by the human thymidine kinase by 5'-aminothymidine and thymidine triphosphate. Thymidine (dThd) kinase is responsible for the initial phosphorylation and, thus, the activation of several anticancer and antiviral drugs, including 3'-azidothymidine (AZT, Zidovudine). Exponentially growing cells were pelleted, homogenized and ultracentrifuged to obtain a clear supernatant with cytosolic thymidine kinase activity. www.aegis.com /aidsline/1995/dec/M95C2623.html   (509 words)

Pharmacokinetic Properties of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors Although the ability of ZDV triphosphate to inhibit HIV reverse transcriptase is 100 times greater than its ability to inhibit host DNA polymerase, the low concentration of thymidine triphosphate in the cell increases the chance that ZDV triphosphate will be used by DNA polymerase, thus causing inhibition of DNA synthesis and potential toxicity. This prolonged carbovir triphosphate half-life is much longer than that previously observed in in vitro studies (3.3 hours) and may be due to a newer assay that directly measures carbovir triphosphate or due to a saturation step and pooling of precursors (carbovir monophosphate or carbovir diphosphate). The intracellular concentration of nucleoside analogue triphosphates is regulated by positive or negative feedback mechanisms on >=1 enzymes in the phosphorylation pathway. www.natap.org /2004/HIV/082304_02.htm   (5587 words)

Title of Invention: Method of DNA sequencing For example, the modified nucleoside triphosphate 5-methyl-deoxycytosine-5'-triphosphate (5-methyl dCTP), will be incorporated into newly synthesized DNA as the modified nucleotide 5-methyl-deoxycytosine-5'-monophosphate (5-methyl dCMP) at positions complementary to guanosine in the template strand but not at positions complementary to adenosine, cytosine or thymidine. Similarly, the suitability of specific modified nucleoside triphosphates with a desired DNA synthesis inducing agent, e.g., a DNA polymerase, may be determined by standard primer extension assays that determine the kinetics of the incorporation of the modified nucleotide in comparison to naturally occurring nucleotides. Modified nucleoside triphosphates selected for use in the invention are capable of substantially protecting newly synthesized DNA of the labeled reaction produces from cleavage by at least one reagent, e.g., a restriction endonuclease or chemical reagent, under conditions to cleave or substantially cleave unmodified DNA. www.nal.usda.gov /bic/Biotech_Patents/1994patents/05354656.html   (10087 words)

Valtrex Drug Description - Valacyclovir - HealthScout The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. Valacyclovir hydrochloride is rapidly converted to acyclovir which has demonstrated antiviral activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella-zoster virus (VZV) both in vitro and in vivo. www.healthscout.com /rxdetail/1/72/1/main.html   (10087 words)

Nucleotide - Wikipedia, the free encyclopedia The nucleobase can be purines or pyrimidines, the sugar can be deoxyribose in DNA or ribose in RNA, and the phosphate chain can be a monophosphate, diphosphate, or triphosphate. Adenosine - Thymidine - Uridine - Guanosine - Cytidine - Deoxyadenosine - Deoxythymidine - Deoxyuridine - Deoxyguanosine - Deoxycytidine - Ribose - Deoxyribose A nucleotide that lacks the phosphate group is called nucleoside. en.wikipedia.org /wiki/Deoxynucleotide   (10087 words)

thymine TMP (thymidine monophosphate), TDP (thymidine diphosphate), and TTP (thymidine triphosphate). Thymidine is significant because of its involvement in the biosynthesis of DNA and in the preservation and transfer of genetic information. Since the thymine nucleotides contain only deoxyribose and not ribose, TTP is the source of thymidine only in deoxyribonucleic acid (DNA); there is no thymine in ribonucleic acid (RNA). www.factmonster.com /ce6/sci/A0848663.html   (10087 words)

RUCs digitale arkiv / RUC's Digital Archive: Item 1800/480 Thymidine kinase (TK) catalyses the ATP-dependent phosphorylation of thymidine to thymidine monophosphate, which is subsequency phosphorylated to thymidine triphosphate and utilized for DNA synthesis. An unchanged affinity for the natural substrate, thymidine, combined with a lower V,,, value suggest that the last 40 amino acids have a structural role or that the ATP binding is disturbed. When ATP is absent from the enzyme, the enzyme appears as a dimer with low affinity for thymidine and when ATP is present the enzyme appears as a tetramer with high affinity for thymidine. www.rucsdigitaleprojektbibliotek.dk /handle/1800/480?mode=full   (10087 words)

Case 2: Discussion - Acyclovir-Resistant Herpes Simplex Virus Infection - Dermatologic Manifestations Acyclovir (Zovirax) requires activation by viral thymidine kinase, the enzyme responsible for the first phosphorylation step in converting acyclovir to its active triphosphorylated form acyclovir triphosphate [1]. All of the drugs that require initial activation by herpes simplex viral kinase (acyclovir, famciclovir, and valacyclovir) are generally ineffective against strains that have absent or decreased thymidine kinase production, as well as drugs that use a similar viral kinase, such as ganciclovir (Cytovene) and valganciclovir (Valcyte). Although prior research in animal models suggested that thymidine kinase-negative herpes simplex virus isolates have decreased virulence [6], several reports have shown that acyclovir-resistant isolates can cause significant clinical disease in humans [7]. depts.washington.edu /hivaids/derm/case2/discussion.html   (571 words)

Plant Gene Register PGR99-048 Mullin BC, Fites RC (1978) Thymidine phosphorylation in Arachis hypogaea by combined activities of adenosine triphosphate phosphohydrolase and nucleoside phosphotransferase. Thymidine kinase (TK) [EC 2.7.1.22] catalyzes dTMP (deoxyribothymidine monophosphate) formation by the monophosphorylation of the 5'-OH group of thymidine using ATP as a phosphate donor. Genes encoding thymidine kinase (TK) have been identified in mammals, prokaryotes, viruses, and certain eukaryotes, although it is not present in Saccharomyces cerevisiae We used this sequence similarity to identify a gene encoding TK from plants. www.tarweed.com /pgr/PGR99-048.html   (634 words)

Attotron Molecular Biology Hypertext Dictionary thymidine triphosphate, a deoxyribose molecule with the pyrimidine thymine attached to the 1´ carbon and a chain of three oxygenated phosphorus atoms attached to the 5' carbon. ddNTP.GIF a nucleoside triphosphate analog that causes termination of an elongating DNA molecule when incorporated by DNA polymerase because of the absence of a 3´-hydroxyl residue on the sugar portion of the compound, which is necessary for the formation of the 3' to 5' phosphate linkage in an elongating DNA chain. The sugar molecules are modified by the presence of a purine or pyrimidine nucleoside or "base" attached to the first, or 1', carbon and the oxygen-phosphorus-oxygen bond links the third, or 3', carbon to the fifth, or 5', carbon of the adjacent sugar molecule. www.attotron.com /pub/dnaquiz/diction.htm   (9688 words)

mknuc Most recently, the thymidine kinase of Equine Herpes Virus type-4 (EHV4-TK) was shown to be superior to HSV1-TK in GCV phosphorylation. Gardberg, A., Shuvalova, L., Monnerjahn, C., Konrad, M., Lavie, A. (2003) Structural basis for the dual thymidine and thymidylate kinase activity of herpes thymidine kinases. Activation to the triphosphate form by cellular kinases is required for drug potency, a fact that in many cases limits the effectiveness of such drugs. www.mpibpc.mpg.de /abteilungen/150/mknuc.htm   (9688 words)

Valtrex Drug Description - Valacyclovir - HealthScout The inhibitory activity of acyclovir is highly selective due to its affinity for the enzyme thymidine kinase (TK) encoded by HSV and VZV. The monophosphate is further converted into diphosphate by cellular guanylate kinase and into triphosphate by a number of cellular enzymes. Valacyclovir hydrochloride is rapidly converted to acyclovir which has demonstrated antiviral activity against herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) and varicella-zoster virus (VZV) both in vitro and in vivo. www.healthscout.com /rxdetail/1/72/1/main.html   (250 words)

Prolonged Depletion of Guanosine Triphosphate Induces Death of Insulin-Secreting Cells by Apoptosis -- Li et al. 139 (9): 3752 -- Endocrinology Prolonged Depletion of Guanosine Triphosphate Induces Death of Insulin-Secreting Cells by Apoptosis -- Li et al. Prolonged Depletion of Guanosine Triphosphate Induces Death of Insulin-Secreting Cells by Apoptosis H]thymidine incorporation was inhibited by adenosine or guanosine endo.endojournals.org /cgi/content/full/139/9/3752   (7341 words)

Unique Metabolism of a Novel Antiviral L-Nucleoside Analog, 2'-Fluoro-5-Methyl-beta -L-Arabinofuranosyluracil: a Substrate for Both Thymidine Kinase and Deoxycytidine Kinase -- Liu et al. 42 (4): 833 -- Antimicrobial Agents and Chemotherapy Purification of deoxythymidine kinase by preparative disc gel electrophoresis and the effects of various halogenated nucleoside triphosphate on its enzymatic activity. The nucleoside analog carbovir was shown to be a substrate for the nucleobase carrier, which is inhibited by adenine. Purification and characterization of the cytoplasmic and mitochondrial isozymes derived from blast cells of acute myelocytic leukemia patients. aac.asm.org /cgi/content/full/42/4/833   (3794 words)

Tramadol, buy tramadol, Ultram, antibiotics, Weight Loss drugs, weight loss herbs, weight loss herbal formula, hair loss, hair growth, DHEA, Lutein, buy Tramadol online, Acyclovir. The recombinant WSSV TK-TMK catalyzed the phosphorylation of thymidine to form thymidine monophosphate (TMP), but we found no evidence that it was able to catalyze the further phosphorylation of TMP to form thymidine diphosphate (or thymidine triphosphate). Chimeric polypeptide of thymidine kinase and thymidylate kinase of shrimp white spot syndrome virus: thymidine kinase activity of the recombinant protein expressed in a baculovirus/insect cell system. In addition to thymidine, of the nine other substrates tested, including acyclovir, ganciclovir, and 5-(2-bromovinyl)-2'-deoxyuridine, only 2'-deoxyuridine and 5-bromo-2'-deoxyuridine could also serve as substrates. darwinpharmacy.com /ref-acyclovir/acyclovir-research-abs3.398.html   (3794 words)

Moravek Biochemicals Table of Contents Thymidine triphosphate - Carbon 14, Carbon 13, Nitrogen 15, and tritium labeled radiochemicals Thymidine monophosphate - Carbon 14 and tritium labeled radiochemicals Thymidine - Carbon 14, Carbon 13, Nitrogen 15, and tritium labeled radiochemicals www.moravek.com /toc.htm   (3794 words)

Structural basis for activation of {alpha}-boranophosphate nucleotide analogues targeting drug-resistant reverse transcriptase -- Meyer et al. 19 (14): 3520 -- The EMBO Journal Tomasz,J., Shaw,B.R., Porter,K. and Sood,A. p -borane-substituted thymidine monophosphate and triphosphate. -borano thymidine 5'-triphosphosphate analogues in the presence of pyrophosphate. Cherfils,J., Moréra,S., Lascu,I., Véron,M. and Janin,J. (1994) X-ray structure of nucleoside diphosphate kinase complexed with thymidine diphosphate and Mg at 2 Å resolution. embojournal.npgjournals.com /cgi/content/full/19/14/3520   (3794 words)

Agripedia, Interactive Multimedia Instructional Agriculture Resources dATP, dGTP, dCTP, and thymidine deoxyribonucleotide triphosphate (dTTP) www.ca.uky.edu /agripedia/classes/ppa660/ppa660L02.asp   (686 words)

Case 2: Discussion - Acyclovir-Resistant Herpes Simplex Virus Infection - Dermatologic Manifestations Acyclovir (Zovirax) requires activation by viral thymidine kinase, the enzyme responsible for the first phosphorylation step in converting acyclovir to its active triphosphorylated form acyclovir triphosphate [1]. Acyclovir triphosphate is present in 40- to 100-fold higher concentrations in herpes simplex virus-infected cells than in uninfected cells. Acyclovir triphosphate has a two-pronged mechanism of action: 1) it competes with 2-deoxyguanosine triphosphate (dGTP) as a substrate for viral DNA polymerase and 2) once it becomes incorporated into the replicating viral DNA, it acts as a chain terminator because it does not have a terminal 3´ hydroxyl group. depts.washington.edu /hivaids/derm/case2/discussion.html   (571 words)

thymine. The Columbia Encyclopedia, Sixth Edition. 2001-05 Combined with the sugar deoxyribose in a glycosidic linkage, thymine forms a derivative called thymidine (a nucleoside), which in turn can be phosphorylated with from one to three phosphoric acid groups, yielding respectively the three nucleotides TMP (thymidine monophosphate), TDP (thymidine diphosphate), and TTP (thymidine triphosphate). Since the thymine nucleotides contain only deoxyribose and not ribose, TTP is the source of thymidine only in deoxyribonucleic acid (DNA); there is no thymine in ribonucleic acid (RNA). Thymine was the first pyrimidine to be purified from a natural source, having been isolated from calf thymus and beef spleen in 1893–4. www.bartleby.com /65/th/thymine.html   (274 words)

Pharmacokinetic Properties of Nucleoside/Nucleotide Reverse Transcriptase Inhibitors Although the ability of ZDV triphosphate to inhibit HIV reverse transcriptase is 100 times greater than its ability to inhibit host DNA polymerase, the low concentration of thymidine triphosphate in the cell increases the chance that ZDV triphosphate will be used by DNA polymerase, thus causing inhibition of DNA synthesis and potential toxicity. The elimination kinetics of carbovir triphosphate produced from either ABC or carbovir were essentially identical. The key parameter is the half-life; however, the plasma elimination half-life of the NRTIs/NtRTIs as administered is of little use in developing a dosing schedule. www.natap.org /2004/HIV/082304_02.htm   (274 words)

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