The effecT of cerTain N-TriTylaTed phenylalanine conjugaTes of amino-adenosine-3’,5’-cyclic monophosphaTe on moloney murine leukaemia virus reverse TranscripTase acTiviTy

Vol. 106 No. 7/8 Page 1 of 5 ABSTRACT 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 HIV1 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-(6aminohexyl) 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.