Resumo

VAN ZYL, Johann M.; ARIATTI, Mario  e  HAWTREY, Arthur O.. The effect of certain N-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on moloney murine leukaemia virus reverse transcriptase activity. S. Afr. j. sci. [online]. 2010, vol.106, n.7-8, pp.1-5. ISSN 1996-7489.

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.

Palavras-chave : inhibitor; Moloney murine leukaemia virus; N-tritylated phenylalanine-nucleotide; reverse transcriptase; ribose-sugar.

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