Inhibition of T4 polynucleotide kinase activity by phosphorothioate and chimeric oligodeoxynucleotides. 1994

R M Teasdale, and S J Matson, and E Fisher, and A M Krieg
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City 52242.

Whole and partially modified phosphorothioate oligodeoxynucleotides (ODN) were found to directly inhibit T4 polynucleotide kinase (PNK) activity, while phosphodiester ODN showed no detectable inhibition. This inhibition was found to be length dependent, as demonstrated by a 28-mer phosphorothioate ODN with an IC50 of 12 nM, and an 8-mer phosphorothioate ODN with an IC50 of 27,000 nM. Inhibition depended on the number and type of modified internucleotide linkages: a 20-mer phosphorothioate ODN had an IC50 of 21 nM, while a chimeric ODN with seven phosphorothioate linkages and an identical sequence showed no inhibition. On the other hand, the same sequence as a chimeric phosphorodithioate ODN (with seven dithioate linkages) had an IC50 of 580 nM. Four different chimeric phosphorodithioate ODN showed markedly different potencies of inhibition, suggesting that inhibition of PNK activity can be sequence specific.

UI MeSH Term Description Entries
D008969 Molecular Sequence Data Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. Sequence Data, Molecular,Molecular Sequencing Data,Data, Molecular Sequence,Data, Molecular Sequencing,Sequencing Data, Molecular
D011116 Polynucleotide 5'-Hydroxyl-Kinase An enzyme that catalyzes the transfer of a phosphate group to the 5'-terminal hydroxyl groups of DNA and RNA. EC 2.7.1.78. Polynucleotide Hydroxylkinase,Polynucleotide Kinase,5'-Hydroxylpolynucleotide Kinase,DNA 5'-Hydroxylkinase,DNA Kinase,Polynucleotide 5'-Hydroxyl Kinase,Polynucleotide Hydroxykinase,5' Hydroxylpolynucleotide Kinase,5'-Hydroxyl Kinase, Polynucleotide,5'-Hydroxyl-Kinase, Polynucleotide,5'-Hydroxylkinase, DNA,DNA 5' Hydroxylkinase,Hydroxykinase, Polynucleotide,Hydroxylkinase, Polynucleotide,Kinase, 5'-Hydroxylpolynucleotide,Kinase, DNA,Kinase, Polynucleotide,Kinase, Polynucleotide 5'-Hydroxyl,Polynucleotide 5' Hydroxyl Kinase
D001483 Base Sequence The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence. DNA Sequence,Nucleotide Sequence,RNA Sequence,DNA Sequences,Base Sequences,Nucleotide Sequences,RNA Sequences,Sequence, Base,Sequence, DNA,Sequence, Nucleotide,Sequence, RNA,Sequences, Base,Sequences, DNA,Sequences, Nucleotide,Sequences, RNA
D013873 Thionucleotides Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
D016376 Oligonucleotides, Antisense Short fragments of DNA or RNA that are used to alter the function of target RNAs or DNAs to which they hybridize. Anti-Sense Oligonucleotide,Antisense Oligonucleotide,Antisense Oligonucleotides,Anti-Sense Oligonucleotides,Anti Sense Oligonucleotide,Anti Sense Oligonucleotides,Oligonucleotide, Anti-Sense,Oligonucleotide, Antisense,Oligonucleotides, Anti-Sense
D017122 Bacteriophage T4 Virulent bacteriophage and type species of the genus T4-like phages, in the family MYOVIRIDAE. It infects E. coli and is the best known of the T-even phages. Its virion contains linear double-stranded DNA, terminally redundant and circularly permuted. Bacteriophage T2,Coliphage T2,Coliphage T4,Enterobacteria phage T2,Enterobacteria phage T4,Phage T2,Phage T4,T2 Phage,T4 Phage,Phage, T2,Phage, T4,Phages, T2,Phages, T4,T2 Phages,T2, Enterobacteria phage,T4 Phages

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