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Inhibition of HIV-associated reverse transcriptase by sugar-modified derivatives of thymidine 5'-triphosphate in comparison to cellular DNA polymerases alpha and beta. 1987

E Matthes, and C Lehmann, and D Scholz, and M von Janta-Lipinski, and K Gaertner, and H A Rosenthal, and P Langen
Central Institute of Molecular Biology, Academy of Sciences of the GDR, Berlin-Buch.

The sugar-modified dTTP analogues 2',3'-didehydro-2',3'-dideoxy-thymidine 5'-triphosphate (ddeTTP), 2',3'-dideoxythymidine 5'-triphosphate (ddTTP), 3'-fluorothymidine 5'-triphosphate (FdTTP), and 3'-azidothymidine 5'-triphosphate (N3dTTP) are demonstrated to be very effective and selective inhibitors of the HIV-associated reverse transcriptase (HIV-RT). This conclusion is based on a comparison of the ID50 values of the compounds for the HIV-RT (ranging from 0.03 microM for ddeTTP to 0.1 microM for ddTTP) and the cellular DNA polymerase alpha (greater than 200 microM). DNA polymerase beta is partially affected by N3dTTP (ID50 = 31 microM) and by the other analogues (ID50 = 1-2.2 microM). FdTTP has proved as effective as N3dTTP (ID50 = 0.05 microM) in suppressing the HIV-RT activity. Kinetic analysis revealed for both dTTP analogues a competitive type of inhibition and the same K1 values (about 0.05 microM).

UI MeSH Term Description Entries
D007700 Kinetics The rate dynamics in chemical or physical systems.
D002460 Cell Line Established cell cultures that have the potential to propagate indefinitely. Cell Lines,Line, Cell,Lines, Cell
D002472 Cell Transformation, Viral An inheritable change in cells manifested by changes in cell division and growth and alterations in cell surface properties. It is induced by infection with a transforming virus. Transformation, Viral Cell,Viral Cell Transformation,Cell Transformations, Viral,Transformations, Viral Cell,Viral Cell Transformations
D004256 DNA Polymerase I A DNA-dependent DNA polymerase characterized in prokaryotes and may be present in higher organisms. It has both 3'-5' and 5'-3' exonuclease activity, but cannot use native double-stranded DNA as template-primer. It is not inhibited by sulfhydryl reagents and is active in both DNA synthesis and repair. DNA Polymerase alpha,DNA-Dependent DNA Polymerase I,Klenow Fragment,DNA Pol I,DNA Dependent DNA Polymerase I,Polymerase alpha, DNA
D004257 DNA Polymerase II A DNA-dependent DNA polymerase characterized in E. coli and other lower organisms. It may be present in higher organisms and has an intrinsic molecular activity only 5% of that of DNA Polymerase I. This polymerase has 3'-5' exonuclease activity, is effective only on duplex DNA with gaps or single-strand ends of less than 100 nucleotides as template, and is inhibited by sulfhydryl reagents. DNA Polymerase epsilon,DNA-Dependent DNA Polymerase II,DNA Pol II,DNA Dependent DNA Polymerase II
D006678 HIV Human immunodeficiency virus. A non-taxonomic and historical term referring to any of two species, specifically HIV-1 and/or HIV-2. Prior to 1986, this was called human T-lymphotropic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV). From 1986-1990, it was an official species called HIV. Since 1991, HIV was no longer considered an official species name; the two species were designated HIV-1 and HIV-2. AIDS Virus,HTLV-III,Human Immunodeficiency Viruses,Human T-Cell Lymphotropic Virus Type III,Human T-Lymphotropic Virus Type III,LAV-HTLV-III,Lymphadenopathy-Associated Virus,Acquired Immune Deficiency Syndrome Virus,Acquired Immunodeficiency Syndrome Virus,Human Immunodeficiency Virus,Human T Cell Lymphotropic Virus Type III,Human T Lymphotropic Virus Type III,Human T-Cell Leukemia Virus Type III,Immunodeficiency Virus, Human,Immunodeficiency Viruses, Human,Virus, Human Immunodeficiency,Viruses, Human Immunodeficiency,AIDS Viruses,Human T Cell Leukemia Virus Type III,Lymphadenopathy Associated Virus,Lymphadenopathy-Associated Viruses,Virus, AIDS,Virus, Lymphadenopathy-Associated,Viruses, AIDS,Viruses, Lymphadenopathy-Associated
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D013329 Structure-Activity Relationship The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups. Relationship, Structure-Activity,Relationships, Structure-Activity,Structure Activity Relationship,Structure-Activity Relationships
D013698 Templates, Genetic Macromolecular molds for the synthesis of complementary macromolecules, as in DNA REPLICATION; GENETIC TRANSCRIPTION of DNA to RNA, and GENETIC TRANSLATION of RNA into POLYPEPTIDES. Genetic Template,Genetic Templates,Template, Genetic
D013942 Thymine Nucleotides Phosphate esters of THYMIDINE in N-glycosidic linkage with ribose or deoxyribose, as occurs in nucleic acids. (From Dorland, 28th ed, p1154) Thymidine Phosphates,Nucleotides, Thymine,Phosphates, Thymidine

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