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Phosphorylation of 5-iodo-5'-amino-2',5',dideoxyuridine by herpes simplex virus type 1 encoded thymidine kinase. 1979

M S Chen, and W H Prusoff

Herpes simplex virus type 1 (HSV-1) encoded thymidine kinase converts 5-iodo-5'-amino-2',5'-dideoxyuridine (AIdUrd), a highly specific anti-herpes agent, into the 5'-diphosphate (AIdUDP) derivative in vitro. AIdUDP was identified by its acid lability, sensitivity to alkaline phosphatase hydrolysis, chromatographic behavior, and ratio of double isotope (125I, 32P) labeling. ATP, but not AMP, is a phosphate donor, and the direct transfer of the beta and gamma phosphate of ATP as pyrophosphate to AIdUrd was ruled out. The presence of a phosphoramidate bond was supported by the acid lability of AIdUDP which has a half life (t1/2) of 320 min at pH 3.0. At neutral pH, the hydrolysis products are AIdUrd and orthophosphate, with AIdUrd monophosphate being the probable hydrolytic intermediate at these pH values. However, at acidic pH, some pyrophosphate was detected in addition to AIdUrd and orthophosphate. AIdUrd competitively inhibited the phosphorylation of thymidine and deoxycytidine. Escherichia coli thymidine kinase, even though 100-fold higher in activity, was unable to phosphorylate AId-Urd under similar incubation conditions.

UI MeSH Term Description Entries
D007065 Idoxuridine An analog of DEOXYURIDINE that inhibits viral DNA synthesis. The drug is used as an antiviral agent. 5-Iodo-2'-deoxyuridine,IUdR,Iododeoxyuridine,5-Iododeoxyuridine,Allergan 211,Herplex Liquifilm,Idoxuridine, 123I-Labeled,Idoxuridine, 125I-Labeled,Idoxuridine, 131I-Labeled,Idoxuridine, 3H-Labeled,Idoxuridine, Radical Ion (+1),Idoxuridine, Radical Ion (1-),Kerecide,NSC-39661,Oftan-IDU,SK&F-14287,Stoxil,123I-Labeled Idoxuridine,125I-Labeled Idoxuridine,131I-Labeled Idoxuridine,3H-Labeled Idoxuridine,5 Iodo 2' deoxyuridine,5 Iododeoxyuridine,Idoxuridine, 123I Labeled,Idoxuridine, 125I Labeled,Idoxuridine, 131I Labeled,Idoxuridine, 3H Labeled,Liquifilm, Herplex,NSC 39661,NSC39661,Oftan IDU,OftanIDU
D007700 Kinetics The rate dynamics in chemical or physical systems.
D010766 Phosphorylation The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety. Phosphorylations
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D003841 Deoxycytidine A nucleoside component of DNA composed of CYTOSINE and DEOXYRIBOSE. Cytosine Deoxyribonucleoside,Cytosine Deoxyriboside,Deoxyribonucleoside, Cytosine,Deoxyriboside, Cytosine
D004790 Enzyme Induction An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis. Induction, Enzyme
D013936 Thymidine A nucleoside in which THYMINE is linked to DEOXYRIBOSE. 2'-Deoxythymidine,Deoxythymidine,2' Deoxythymidine
D013937 Thymidine Kinase An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC 2.7.1.21. Deoxythymidine Kinase,Deoxypyrimidine Kinase,Kinase, Deoxypyrimidine,Kinase, Deoxythymidine,Kinase, Thymidine
D018139 Simplexvirus A genus of the family HERPESVIRIDAE, subfamily ALPHAHERPESVIRINAE, consisting of herpes simplex-like viruses. The type species is HERPESVIRUS 1, HUMAN. Herpes Simplex Virus,Herpesvirus 1, Saimiriine,Herpesvirus 1, Saimirine,Herpesvirus 16, Cercopithecine,Marmoset Virus,Cercopithecine Herpesvirus 16,Herpes Labialis Virus,Herpes-T Virus,Herpesvirus 1 (alpha), Saimirine,Herpesvirus Hominis,Herpesvirus Papio 2,Herpesvirus Platyrhinae,Marmoset Herpesvirus,Saimiriine Herpesvirus 1,Herpes Labialis Viruses,Herpes Simplex Viruses,Herpes T Virus,Herpes-T Viruses,Herpesvirus Homini,Herpesvirus, Marmoset,Herpesviruses, Marmoset,Homini, Herpesvirus,Hominis, Herpesvirus,Labialis Virus, Herpes,Labialis Viruses, Herpes,Marmoset Herpesviruses,Marmoset Viruses,Platyrhinae, Herpesvirus,Saimirine Herpesvirus 1,Simplexviruses,Virus, Herpes Labialis,Viruses, Herpes Labialis

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