The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity
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 gen...
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| Format: | Article |
| Language: | English |
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Academy of Science of South Africa
2010-07-01
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| Series: | South African Journal of Science |
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| Online Access: | http://192.168.0.118/index.php/sajs/article/view/9942 |
| _version_ | 1819116891548942336 |
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| author | Johann van Zyl Mario Ariatti Arthur Hawtrey |
| author_facet | Johann van Zyl Mario Ariatti Arthur Hawtrey |
| author_sort | Johann van Zyl |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T05:24:17Z |
| format | Article |
| id | doaj.art-3752c84acc904afd85b5c4beade990c5 |
| institution | Directory Open Access Journal |
| issn | 1996-7489 |
| language | English |
| last_indexed | 2024-12-22T05:24:17Z |
| publishDate | 2010-07-01 |
| publisher | Academy of Science of South Africa |
| record_format | Article |
| series | South African Journal of Science |
| spelling | doaj.art-3752c84acc904afd85b5c4beade990c52022-12-21T18:37:38ZengAcademy of Science of South AfricaSouth African Journal of Science1996-74892010-07-011067/8The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activityJohann van Zyl0Mario Ariatti1Arthur Hawtrey2Stellenbosch UniversityUniversity of KwaZula-NatalStellenbosch UniversityMoloney 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.http://192.168.0.118/index.php/sajs/article/view/9942inhibitorMoloney murine leukaemia virusN-tritylated phenylalanine-nucleotidereverse transcriptaseribose-sugar |
| spellingShingle | Johann van Zyl Mario Ariatti Arthur Hawtrey The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity South African Journal of Science inhibitor Moloney murine leukaemia virus N-tritylated phenylalanine-nucleotide reverse transcriptase ribose-sugar |
| title | The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity |
| title_full | The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity |
| title_fullStr | The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity |
| title_full_unstemmed | The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity |
| title_short | The effect of certain <i>N</i>-tritylated phenylalanine conjugates of amino-adenosine-3',5'-cyclic monophosphate on Moloney murine leukaemia virus reverse transcriptase activity |
| title_sort | effect of certain i n i tritylated phenylalanine conjugates of amino adenosine 3 5 cyclic monophosphate on moloney murine leukaemia virus reverse transcriptase activity |
| topic | inhibitor Moloney murine leukaemia virus N-tritylated phenylalanine-nucleotide reverse transcriptase ribose-sugar |
| url | http://192.168.0.118/index.php/sajs/article/view/9942 |
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