The effect of certain N-tritylated phenylalanine conjugates of amino-adenosine-3’,5’-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity
| Autor: | Johann M. van Zyl, Mario Ariatti, Arthur O. Hawtrey |
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| Jazyk: | angličtina |
| Rok vydání: | 2010 |
| Předmět: | |
| Zdroj: | South African Journal of Science, Vol 106, Iss 7/8 (2010) |
| Druh dokumentu: | article |
| ISSN: | 0038-2353 1996-7489 |
| DOI: | 10.4102/sajs.v106i7/8.195 |
| Popis: | Moloney murine leukaemia virus (M-MuLV) is a member of the retrovirus family. Its cloned reverse transcriptase (RT), similarly to HIV type 1 reverse transcriptase (HIV-1 RT), exhibits DNA-polymerase and ribonuclease H (RNase H) activities capable of converting the single-stranded retroviral RNA genome into double-stranded DNA. The latter is then integrated into the host chromosome during viral infection. M-MuLV RT is, therefore, an attractive enzyme to help understand mutations in HIV-1 RT and its use in inhibition studies can help facilitate new drug designs. In this study, conjugates consisting of N-trityl derivatives of p-fluoro, p-nitro and p-iodo-DL-phenylalanine were coupled to 8-(6-aminohexyl) amino-adenosine-3’,5’-cyclic monophosphate and examined for their effect on DNA synthesis by M-MuLV RT. Synthesis was studied in a system containing poly (rA).oligo d(pT)15 as a template-primer with [3H] dTTP. The iodo-derivative, N-trityl-p-iodo-DL-phenylalanine-8-(6-aminohexyl) amino-adenosine-3’,5’-cyclic monophosphate was found to be a very active inhibitor of the RT enzyme (IC50 = 1 µM), while the p-nitro (IC50 = 45 µM) and p-fluoro (IC50 = 65 µM) were weak inhibitors. Further work will be aimed at determining the mode of binding of the N-tritylated conjugates and also of various substituted amino acids and short peptides to M-MuLV RT to elucidate the mechanisms of inhibition. |
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