Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.1.21 (thymidine kinase)
 7,561 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A new method has been devised to measure the number of base pairs per helical turn along any DNA molecule in solution. A DNA restriction fragment is adsorbed onto crystalline calcium phosphate, fragmented by reaction with iron(II) EDTA, and subjected to electrophoresis on a denaturing polyacrylamide gel. A modulated cutting pattern results, which gives directly the helical periodicity of the DNA molecule. A 150-base pair sequence directly upstream of the thymidine kinase gene of the type 1 herpes simplex virus was found to have an overall helical twist of 10.5 base pairs per turn, which is characteristic of the B conformation of DNA. In addition, purines 3' to pyrimidines showed lower than expected reactivity toward the iron cutting reagent, which is evidence for sequence-dependent variability in DNA conformation.
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PMID:Iron(II) EDTA used to measure the helical twist along any DNA molecule. 299 45

We report the synthesis of novel 1-(2'-deoxy-4'-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides and the subsequent preparation of a series of N3-substituted analogues. All the novel compounds were evaluated against a range of viruses, however they lacked any measurable activity. The lack of anti-herpetic activity may be a result of the parent nucleoside having poor affinity for herpes simplex virus type 1 thymidine kinase. Conformational analysis of the parent nucleoside showed a twist (3T2) sugar conformation commonly displayed by 2'-deoxy-4'-thionucleosides and the anti-human immunodeficiency virus type 1 agents zidovudine and 3'-fluoro-ddT.
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PMID:Novel 6-azapyrimidine-2'-deoxy-4'-thionucleosides: synthesis, biological evaluation and conformational analysis. 1057 79

The synthesis of a series of novel 1-(2-deoxy-4-thio-beta-D-erythro-pentofuranosyl)-(6-azapyrimidine) nucleosides is described. X-ray crystallographic data of the thymidine derivative allowed conformational analysis, which indicated a twist (3T2) sugar conformation. Hydrogen-bonded assemblies for the crystal structure were determined using PLATON software to allow further interpretation of the crystal packing and base interactions. The 6-azapyrimidine nucleosides described were evaluated against a range of viral strains. The thymidine analogue showed pronounced activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2), varicella-zoster virus (VZV), and vaccinia virus. This compound lost only 5- to 10-fold of its antiviral activity against thymidine kinase (TK)-deficient HSV-1 and VZV strains. These observations suggest that the compounds may not entirely depend on viral TK-catalyzed phosphorylation for antiviral activity and/or use an alternative metabolic activation pathway, and/or display a unique mechanism of antiviral action by the unmetabolized nucleoside analogue.
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PMID:6-azapyrimidine-2'-deoxy-4'-thionucleosides: antiviral agents against TK+ and TK- HSV and VZV strains. 1548 85