Inhibition of reverse transcriptase activity by 2′,3′-dideoxythymidine 5′-triphosphate and its derivatives modified on the 3′ position
| Autor: | Takeshi Fujii, Katsuhiko Ono, Hideo Nakane, Masako Ogasawara, Mineo Saneyoshi, Yukari Iwata, Kazuhiko Sawai |
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| Rok vydání: | 1986 |
| Předmět: |
viruses
Kinetics Biophysics Binding Competitive Rauscher Virus Biochemistry Substrate Specificity Structure-Activity Relationship chemistry.chemical_compound Murine leukemia virus Ribose Thymine Nucleotides Structure–activity relationship Moiety Molecular Biology biology Substrate (chemistry) RNA-Directed DNA Polymerase Cell Biology biology.organism_classification Molecular biology Reverse transcriptase chemistry Reverse Transcriptase Inhibitors Primer (molecular biology) Dideoxynucleotides |
| Zdroj: | Biochemical and Biophysical Research Communications. 140:498-507 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/0006-291x(86)90760-6 |
| Popis: | Inhibitory effects of 2',3'-dideoxythymidine 5'-triphosphate (ddTTP) and its three derivatives modified on the 3' position of ribose moiety [3'-azido-2',3'-dideoxythymidine 5'-triphosphate (3'-N3-ddTTP), 3'-amino-2',3'-dideoxythymidine 5'-triphosphate (3'-NH2-ddTTP) and 2'-deoxyxylo-furanosylthymine 5'-triphosphate (dXTP)] on the activity of the reverse transcriptase purified from Rauscher murine leukemia virus were examined and compared with each other. When (rA)n X (dT)12-18 was used as the template X primer in the presence of manganese ion, all these compounds except 3'-NH2-ddTTP inhibited the reverse transcriptase activity in competitive fashion with respect to the dTTP substrate. The inhibition potentials of these compounds are ordered as follows: 3'-N3-ddTTP (Ki = 1.8 microM) greater than ddTTP (Ki = 9.3 microM) greater than dXTP (Ki = 16.3 microM), and the Ki values of these inhibitors are smaller than the Km of dTTP (30 microM). The observed inhibitions were mainly due to competition between the dTTP substrate and inhibitor rather than chain-termination of the elongating DNAs caused by incorporation of these dideoxy compounds. |
| Databáze: | OpenAIRE |
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