13C NMR (400 MHz, Compact disc3OD): 166.24, 152.18, 144.15, 142.65, 124.72, 102.82, 87.19, 86.62, 62.19, 61.26, 46.09, 39.26. 17. (dd, = 3.2 and 12.4 Hz, 1H), 3.73 (dd, = 3.6 and 12.4 Hz, 1H), 2.86 (m, 1H), 2.69 (m, 1H), 1.88 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 165.21, 151.10, 142.87, 137.06, 123.49, 110.48, 85.48, 85.16, 60.91, 59.95, 44.82, 37.82, 11.29. 18. = 7.2 Hz, 1H), 7.93 (s, 1H), 6.41 (t, = 6.4 Hz, 1H), 5.93 (d, = 7.2 Hz, 1H), 5.35 (dt, = 5.6 and 8.4 Hz, 1H), 4.39 (dt, = 3.2 and 6.0 Hz, 1H), 3.89 (dd, = 3.2 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.37 (t, = 6.8 Hz, 2H), 2.97 (m, 1H), 2.80 (t, = 7.6 Hz, 2H), 2.65 (ddd, = 5.6, 8.4 and 14.0 Hz, 1H), 1.95 (quin, = 6.8 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.78, 158.20, 148.34, 142.82, 123.07, 96.12, 87.97, 86.55, 62.08, 60.78, 51.73, 39.90, 29.67, 23.48. 19. = 0.8 Hz, 1H), 7.93 (s, 1H), 6.43 (t, = 6.0 Hz, 1H), 5.36 (dt, = 6.0 and 8.8 Hz, 1H), 4.38 (dt, = 3.2 and 6.0 Hz, 1H), 3.92 (dd, = 2.8 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.36 (t, = 6.8 Hz, 2H), 2.95 (m, 1H), 2.80 (t, = 7.2 Hz, 2H), 2.65 (ddd, = 6.0, 8.8 and 14.0 Hz, 1H), 1.99 (d, = 0.8 Hz, 3H), 1.94 (quin, = 7.2 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.43, 158.26, 148.32, 140.21, 123.07, 104.46, 87.67, 86.46, 62.46, 60.69, 51.73, 39.82, 29.68, 23.49, 13.40. 20. = 1.2 Hz, 1H), 7.78 (s, 1H), 6.58 (t, = 6.8 Hz, 1H), 5.30 (m, 1H), 4.66 (d, = 3.6 Hz, 2H), 4.36 (q, = 2.8 Hz, 1H), 3.85 (dd, = 3.2 and 11.8 Hz, 1H), 3.74 (dd, = 3.2 and 12.2 Hz, 1H), 2.79 (m, 1H), 2.66 (m, 1H), 1.90 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 184.63, 151.18, 137.05, 133.40, 133.10, 110.54, 85.97, 85.47, 61.32, 58.38, 41.81, 38.11, 11.29. 21. Schinazi RF; Sommadossi JP; Saalman V; Cannon DL; Xie M-W; Hart GC; Hahn EF Actions of 3-azido-3-deoxythymidine nucleotide dimers in major lymphocytes contaminated with human being immunodeficiency disease type 1. Antimicrob. Real estate agents Chemother 1990, 34, 1061C1067. [PMC free of charge content] [PubMed] [Google Scholar] 22. Stuyver LJ; Lostia S; Adams M; Mathew J; Pai BS; Grier J; Tharnish PM; Choi Y; Chong Y; Choo H; Chu CK; Otto MJ; Schinazi RF Antiviral actions and mobile toxicities of revised 2,3-dideoxy-2,3-didehydrocytidine analogues. Antimicrob. Real estate agents Chemother 2002, 46, 3854C3860. [PMC free of charge content] [PubMed] [Google Scholar] 23. Burgess K; Make D AMZ30 Syntheses of nucleoside triphosphates. Chem. Rev 2000, 100, 2047C2060. [PubMed] [Google Scholar] 24. a) Sluis-Cremer N; Sheen C-W; Zelina S; Argoti Torres PS; Parikh UM; Mellors JW Molecular system where the K70E mutation in human being immunodeficiency disease type 1 invert transcriptase confers level of resistance to nucleoside invert transcriptase inhibitors. Antimicrob. Real estate agents Chemother 2007, 51, 48C53 [PMC free of charge content] [PubMed] [Google Scholar]b) Parikh UM; Zelina S; Sluis-Cremer N; Mellors JW Molecular systems of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 invert transcriptase. Helps 2007, 21, 1405C1414 [PubMed] [Google Scholar]c) Sluis-Cremer N; Arion D; Parikh U; Koontz D; Schinazi RF; Mellors JW; Parniak MA Enzyme regulation and catalysis. J. Biol. Chem 2005, 280, 29047C29052. [PubMed] [Google Scholar] 25. Wildtype (WT) HIV-1 (LAI) change transcriptase (RT) was purified as referred to previously. The proteins focus from the purified enzyme was established at 280 nm using an extinction coefficient ( em spectrophotometrically ? /em 280) of 260450 M?1 cm?1, and by Bradford proteins assays (Sigma-Aldrich, St. Louis, MO, USA). AZT-TP was bought from TriLink Biotechnologies, Inc (NORTH PARK, CA, USA), dNTPs had been obtained from GE Health care (Piscataway, NJ, USA), and [ em /em -32P] ATP was from PerkinElmer Existence Sciences (Boston, MA, USA). DNA oligonucleotides had been synthesized by IDT (Coralville, IA, USA). The power of 3-triazole thymidine analogues to inhibit HIV-1 RT DNA synthesis was examined utilizing a DNA/DNA template/primer (T/Ps)..13C NMR (400 MHz, Compact disc3OD): 167.78, 158.20, 148.34, 142.82, 123.07, 96.12, 87.97, 86.55, 62.08, 60.78, 51.73, 39.90, 29.67, 23.48. 19. Hz, 1H), 2.86 (m, 1H), 2.69 (m, 1H), 1.88 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 165.21, 151.10, 142.87, 137.06, 123.49, 110.48, 85.48, 85.16, 60.91, 59.95, 44.82, 37.82, 11.29. 18. = 7.2 Hz, 1H), 7.93 (s, 1H), 6.41 (t, = 6.4 Hz, 1H), 5.93 (d, = 7.2 Hz, 1H), 5.35 (dt, = 5.6 and 8.4 Hz, 1H), 4.39 (dt, = 3.2 and 6.0 Hz, 1H), 3.89 (dd, = 3.2 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.37 (t, = 6.8 Hz, 2H), 2.97 (m, 1H), 2.80 (t, = 7.6 Hz, 2H), 2.65 (ddd, = 5.6, 8.4 and 14.0 Hz, 1H), 1.95 (quin, = 6.8 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.78, 158.20, 148.34, 142.82, 123.07, 96.12, 87.97, 86.55, 62.08, 60.78, 51.73, 39.90, 29.67, 23.48. 19. = AMZ30 0.8 Hz, 1H), 7.93 (s, 1H), 6.43 (t, = 6.0 Hz, 1H), 5.36 (dt, = 6.0 and 8.8 Hz, 1H), 4.38 (dt, = 3.2 and 6.0 Hz, 1H), 3.92 (dd, = 2.8 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.36 (t, = 6.8 Hz, 2H), 2.95 (m, 1H), 2.80 (t, = 7.2 Hz, 2H), 2.65 (ddd, = 6.0, 8.8 and 14.0 Hz, 1H), 1.99 (d, = 0.8 Hz, 3H), 1.94 (quin, = 7.2 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.43, 158.26, 148.32, 140.21, 123.07, 104.46, 87.67, 86.46, 62.46, 60.69, 51.73, 39.82, 29.68, 23.49, 13.40. 20. = 1.2 Hz, 1H), 7.78 (s, 1H), 6.58 (t, = 6.8 Hz, 1H), 5.30 (m, 1H), 4.66 (d, = 3.6 Hz, 2H), 4.36 (q, = 2.8 Hz, 1H), 3.85 (dd, = 3.2 and 11.8 Hz, 1H), 3.74 (dd, = 3.2 and 12.2 Hz, 1H), 2.79 (m, 1H), 2.66 (m, 1H), 1.90 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 184.63, 151.18, 137.05, 133.40, 133.10, 110.54, 85.97, 85.47, 61.32, 58.38, 41.81, 38.11, 11.29. 21. Schinazi RF; Sommadossi JP; Saalman V; Cannon DL; Xie M-W; Hart GC; Hahn EF Actions of 3-azido-3-deoxythymidine nucleotide dimers in major lymphocytes contaminated with human being immunodeficiency disease type 1. Antimicrob. Real estate agents Chemother 1990, 34, 1061C1067. [PMC free of charge content] [PubMed] [Google Scholar] 22. Stuyver LJ; Lostia S; Adams M; Mathew J; Pai BS; Grier J; Tharnish PM; Choi Y; Chong Y; Choo H; Chu CK; Otto MJ; Schinazi RF Antiviral actions and mobile toxicities of revised 2,3-dideoxy-2,3-didehydrocytidine analogues. Antimicrob. Real estate agents Chemother 2002, 46, 3854C3860. [PMC free of charge content] [PubMed] [Google Scholar] 23. Burgess K; Make D Syntheses of nucleoside triphosphates. Chem. Rev 2000, 100, 2047C2060. [PubMed] [Google Scholar] 24. a) Sluis-Cremer N; Sheen C-W; Zelina S; Argoti Torres PS; Parikh UM; Mellors JW Molecular system where the K70E mutation in human being immunodeficiency disease type 1 invert transcriptase confers level of resistance to nucleoside invert transcriptase inhibitors. Antimicrob. Real estate agents Chemother 2007, 51, 48C53 [PMC free of charge content] [PubMed] [Google Scholar]b) Parikh UM; Zelina S; Sluis-Cremer N; Mellors JW Molecular systems of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 invert transcriptase. Helps 2007, 21, 1405C1414 [PubMed] [Google Scholar]c) Sluis-Cremer N; Arion D; Parikh U; Koontz D; Schinazi RF; Mellors JW; Parniak MA Enzyme catalysis and rules. J. Biol. Chem 2005, 280, 29047C29052. [PubMed] [Google Scholar] 25. Wildtype (WT) HIV-1 (LAI) change transcriptase (RT) was purified as referred to previously. The proteins concentration from the purified enzyme was established spectrophotometrically at 280 nm using an extinction coefficient ( em ? /em 280) of 260450 M?1 cm?1, and by Bradford proteins assays (Sigma-Aldrich, St. Louis, MO, USA). AZT-TP was bought from TriLink Biotechnologies, Inc (NORTH PARK, CA, USA), dNTPs had been obtained from GE Health care (Piscataway, NJ, USA), and [ em /em -32P] ATP was from PerkinElmer Existence Sciences (Boston, MA, USA)..13C NMR (400 MHz, Compact disc3OD): 184.63, 151.18, 137.05, 133.40, 133.10, 110.54, 85.97, 85.47, 61.32, 58.38, 41.81, 38.11, 11.29. 21. and 12.2 Hz, 1H), 2.95 (m, 1H), 2.76 (ddd, = 6.0, 8.4 and 14.4 Hz, 1H). 13C NMR (400 MHz, Compact disc3OD): 166.24, 152.18, 144.15, 142.65, 124.72, 102.82, 87.19, 86.62, 62.19, 61.26, 46.09, 39.26. 17. = 1.2 Hz, 1H), 6.45 (t, = 6.4 Hz, 1H), 5.40 (m, 1H), 4.47 (s, 2H), 4.33 (m, 1H), 3.86 (dd, = 3.2 and 12.4 Hz, 1H), 3.73 (dd, = 3.6 and 12.4 Hz, 1H), 2.86 (m, 1H), 2.69 (m, 1H), 1.88 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 165.21, 151.10, 142.87, 137.06, 123.49, 110.48, 85.48, 85.16, 60.91, 59.95, 44.82, 37.82, 11.29. 18. = 7.2 Hz, 1H), 7.93 (s, 1H), 6.41 (t, = 6.4 Hz, 1H), 5.93 (d, = 7.2 Hz, 1H), 5.35 (dt, = 5.6 and 8.4 Hz, 1H), 4.39 (dt, = 3.2 and 6.0 Hz, 1H), 3.89 (dd, = 3.2 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.37 (t, = 6.8 Hz, 2H), 2.97 (m, 1H), 2.80 (t, = 7.6 Hz, 2H), 2.65 (ddd, = 5.6, 8.4 and 14.0 Hz, 1H), 1.95 (quin, = 6.8 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.78, 158.20, 148.34, 142.82, 123.07, 96.12, 87.97, 86.55, 62.08, 60.78, 51.73, 39.90, 29.67, 23.48. 19. = 0.8 Hz, 1H), 7.93 (s, 1H), 6.43 (t, = 6.0 Hz, 1H), 5.36 (dt, = 6.0 and 8.8 Hz, 1H), 4.38 (dt, = 3.2 and 6.0 Hz, 1H), 3.92 (dd, = 2.8 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.36 (t, = 6.8 Hz, 2H), 2.95 (m, 1H), 2.80 (t, = 7.2 Hz, 2H), 2.65 (ddd, = 6.0, 8.8 and 14.0 Hz, 1H), 1.99 (d, = 0.8 Hz, 3H), 1.94 (quin, = 7.2 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.43, 158.26, 148.32, 140.21, 123.07, 104.46, 87.67, 86.46, 62.46, 60.69, 51.73, 39.82, 29.68, 23.49, 13.40. 20. = 1.2 Hz, 1H), 7.78 (s, 1H), 6.58 (t, = 6.8 Hz, 1H), 5.30 (m, 1H), 4.66 (d, = 3.6 Hz, 2H), 4.36 (q, = 2.8 Hz, 1H), 3.85 AMZ30 (dd, = 3.2 and 11.8 Hz, 1H), 3.74 (dd, = 3.2 and 12.2 Hz, 1H), 2.79 (m, 1H), 2.66 (m, 1H), 1.90 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 184.63, 151.18, 137.05, 133.40, 133.10, 110.54, 85.97, 85.47, 61.32, 58.38, 41.81, 38.11, 11.29. 21. Schinazi RF; Sommadossi JP; Saalman V; Cannon DL; Xie M-W; Hart GC; Hahn EF Actions of 3-azido-3-deoxythymidine nucleotide dimers in major lymphocytes contaminated with human being immunodeficiency disease type 1. Antimicrob. Real estate agents Chemother 1990, 34, 1061C1067. [PMC free of charge content] [PubMed] [Google Scholar] 22. Stuyver LJ; Lostia S; Adams M; Mathew J; Pai BS; Grier J; Tharnish PM; Choi Y; Chong Y; Choo H; Chu CK; Otto MJ; Schinazi RF Antiviral actions and mobile toxicities of revised 2,3-dideoxy-2,3-didehydrocytidine analogues. Antimicrob. Real estate agents Chemother 2002, 46, 3854C3860. [PMC free of charge content] [PubMed] [Google Scholar] 23. Burgess K; Make D Syntheses of nucleoside triphosphates. Chem. Rev 2000, 100, 2047C2060. [PubMed] [Google Scholar] 24. a) Sluis-Cremer N; Sheen C-W; Zelina S; Argoti Torres PS; Parikh UM; Mellors JW Molecular system where the K70E mutation in human being immunodeficiency disease type 1 invert transcriptase confers level of resistance to nucleoside invert transcriptase inhibitors. Antimicrob. Real estate agents Chemother 2007, 51, 48C53 [PMC free of charge content] [PubMed] [Google Scholar]b) Parikh UM; Zelina S; Sluis-Cremer N; Mellors JW Molecular systems of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 invert transcriptase. Helps 2007, 21, 1405C1414 [PubMed] [Google Scholar]c) Sluis-Cremer N; Arion D; Parikh U; Koontz D; Schinazi RF; Mellors JW; Parniak MA Enzyme catalysis and rules. J. Biol. Chem 2005, 280, 29047C29052. [PubMed] [Google Scholar] 25..The power of 3-triazole thymidine analogues to inhibit HIV-1 RT DNA synthesis was evaluated utilizing a DNA/DNA template/primer (T/Ps). 46.09, 39.26. 17. = 1.2 Hz, 1H), 6.45 (t, = 6.4 Hz, 1H), 5.40 (m, 1H), 4.47 (s, 2H), 4.33 (m, 1H), 3.86 (dd, = 3.2 and 12.4 Hz, 1H), 3.73 (dd, = 3.6 and 12.4 Hz, 1H), 2.86 (m, 1H), 2.69 (m, 1H), 1.88 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 165.21, 151.10, 142.87, 137.06, 123.49, 110.48, 85.48, 85.16, 60.91, 59.95, 44.82, 37.82, 11.29. 18. = 7.2 Hz, 1H), 7.93 (s, 1H), 6.41 (t, = 6.4 Hz, 1H), 5.93 (d, = 7.2 Hz, 1H), 5.35 (dt, = 5.6 and 8.4 Hz, 1H), 4.39 (dt, = 3.2 and 6.0 Hz, 1H), 3.89 (dd, = 3.2 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.37 (t, = 6.8 Hz, 2H), 2.97 (m, 1H), 2.80 (t, = 7.6 Hz, 2H), 2.65 (ddd, = 5.6, 8.4 and 14.0 Hz, 1H), 1.95 (quin, = 6.8 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.78, 158.20, 148.34, 142.82, Goat polyclonal to IgG (H+L) 123.07, 96.12, 87.97, 86.55, 62.08, 60.78, 51.73, 39.90, 29.67, 23.48. 19. = 0.8 Hz, 1H), 7.93 (s, 1H), 6.43 (t, = 6.0 Hz, 1H), 5.36 (dt, = 6.0 and 8.8 Hz, 1H), 4.38 (dt, = 3.2 and 6.0 Hz, 1H), 3.92 (dd, = 2.8 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.36 (t, = 6.8 Hz, 2H), 2.95 (m, 1H), 2.80 (t, = 7.2 Hz, 2H), 2.65 (ddd, = 6.0, 8.8 and 14.0 Hz, 1H), 1.99 (d, = 0.8 Hz, 3H), 1.94 (quin, = 7.2 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.43, 158.26, 148.32, 140.21, 123.07, 104.46, 87.67, 86.46, 62.46, 60.69, 51.73, 39.82, 29.68, 23.49, 13.40. 20. = 1.2 Hz, 1H), 7.78 (s, 1H), 6.58 (t, = 6.8 Hz, 1H), 5.30 (m, 1H), 4.66 (d, = 3.6 Hz, 2H), 4.36 (q, = 2.8 Hz, 1H), 3.85 (dd, = 3.2 and 11.8 Hz, 1H), 3.74 (dd, = 3.2 and 12.2 Hz, 1H), 2.79 (m, 1H), 2.66 (m, 1H), 1.90 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 184.63, 151.18, 137.05, 133.40, 133.10, 110.54, 85.97, 85.47, 61.32, 58.38, 41.81, 38.11, 11.29. 21. Schinazi RF; Sommadossi JP; Saalman V; Cannon DL; Xie M-W; Hart GC; Hahn EF Actions of 3-azido-3-deoxythymidine nucleotide dimers in principal lymphocytes contaminated with individual immunodeficiency trojan type 1. Antimicrob. Realtors Chemother 1990, 34, 1061C1067. [PMC free of charge content] [PubMed] [Google Scholar] 22. Stuyver LJ; Lostia S; Adams M; Mathew J; Pai BS; Grier J; Tharnish PM; Choi Y; Chong Y; Choo H; Chu CK; Otto MJ; Schinazi RF Antiviral actions and mobile toxicities of improved 2,3-dideoxy-2,3-didehydrocytidine analogues. Antimicrob. Realtors Chemother 2002, 46, 3854C3860. [PMC free of charge content] [PubMed] [Google Scholar] 23. Burgess K; Make D Syntheses of nucleoside triphosphates. Chem. Rev 2000, 100, 2047C2060. [PubMed] [Google Scholar] 24. a) Sluis-Cremer N; Sheen C-W; Zelina S; Argoti Torres PS; Parikh UM; Mellors JW Molecular system where the K70E mutation in individual immunodeficiency trojan type 1 invert transcriptase confers level of resistance to nucleoside invert transcriptase inhibitors. Antimicrob. Realtors Chemother 2007, 51, 48C53 [PMC free of charge content] AMZ30 [PubMed] [Google Scholar]b) Parikh UM; Zelina S; Sluis-Cremer N; Mellors JW Molecular systems of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 invert transcriptase. Helps 2007, 21, 1405C1414 [PubMed] [Google Scholar]c) Sluis-Cremer N; Arion D; Parikh U; Koontz D; Schinazi RF; Mellors JW; Parniak MA Enzyme catalysis and legislation. J. Biol. Chem 2005, 280, 29047C29052. [PubMed] [Google Scholar] 25. Wildtype (WT) HIV-1 (LAI) change transcriptase (RT) was purified as defined previously. The proteins concentration from the purified enzyme was driven spectrophotometrically at 280 nm using an extinction coefficient ( em ? /em 280) of 260450 M?1 cm?1, and by Bradford proteins assays (Sigma-Aldrich, St. Louis, MO, USA). AZT-TP was bought from TriLink Biotechnologies, Inc (NORTH PARK, CA, USA), dNTPs had been obtained from GE Health care (Piscataway, NJ, USA), and [ em /em -32P] ATP was extracted from PerkinElmer Lifestyle Sciences (Boston, MA, USA). DNA oligonucleotides had been synthesized by IDT (Coralville, IA, USA). The power of 3-triazole thymidine analogues to inhibit HIV-1 RT DNA synthesis was examined utilizing a DNA/DNA template/primer.Louis, MO, USA). and 12.4 Hz, 1H), 3.73 (dd, = 3.6 and 12.4 Hz, 1H), 2.86 (m, 1H), 2.69 (m, 1H), 1.88 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 165.21, 151.10, 142.87, 137.06, 123.49, 110.48, 85.48, 85.16, 60.91, 59.95, 44.82, 37.82, 11.29. 18. = 7.2 Hz, 1H), 7.93 (s, 1H), 6.41 (t, = 6.4 Hz, 1H), 5.93 (d, = 7.2 Hz, 1H), 5.35 (dt, = 5.6 and 8.4 Hz, 1H), 4.39 (dt, = 3.2 and 6.0 Hz, 1H), 3.89 (dd, = 3.2 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.37 (t, = 6.8 Hz, 2H), 2.97 (m, 1H), 2.80 (t, = 7.6 Hz, 2H), 2.65 (ddd, = 5.6, 8.4 and 14.0 Hz, 1H), 1.95 (quin, = 6.8 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.78, 158.20, 148.34, 142.82, 123.07, 96.12, 87.97, 86.55, 62.08, 60.78, 51.73, 39.90, 29.67, 23.48. 19. = 0.8 Hz, 1H), 7.93 (s, 1H), 6.43 (t, = 6.0 Hz, 1H), 5.36 (dt, = 6.0 and 8.8 Hz, 1H), 4.38 (dt, = 3.2 and 6.0 Hz, 1H), 3.92 (dd, = 2.8 and 12.4 Hz, 1H), 3.76 (dd, = 3.2 and 12.4 Hz, 1H), 3.36 (t, = 6.8 Hz, 2H), 2.95 (m, 1H), 2.80 (t, = 7.2 Hz, 2H), 2.65 (ddd, = 6.0, 8.8 and 14.0 Hz, 1H), 1.99 (d, = 0.8 Hz, 3H), 1.94 (quin, = 7.2 Hz, 2H). 13C NMR (400 MHz, Compact disc3OD): 167.43, 158.26, 148.32, 140.21, 123.07, 104.46, 87.67, 86.46, 62.46, 60.69, 51.73, 39.82, 29.68, 23.49, 13.40. 20. = 1.2 Hz, 1H), 7.78 (s, 1H), 6.58 (t, = 6.8 Hz, 1H), 5.30 (m, 1H), 4.66 (d, = 3.6 Hz, 2H), 4.36 (q, = 2.8 Hz, 1H), 3.85 (dd, = 3.2 and 11.8 Hz, 1H), 3.74 (dd, = 3.2 and 12.2 Hz, 1H), 2.79 (m, 1H), 2.66 (m, 1H), 1.90 (d, = 1.2 Hz, 3H). 13C NMR (400 MHz, Compact disc3OD): 184.63, 151.18, 137.05, 133.40, 133.10, 110.54, 85.97, 85.47, 61.32, 58.38, 41.81, 38.11, 11.29. 21. Schinazi RF; Sommadossi JP; Saalman V; Cannon DL; Xie M-W; Hart GC; Hahn EF Actions of 3-azido-3-deoxythymidine nucleotide dimers in principal lymphocytes contaminated with individual immunodeficiency trojan type 1. Antimicrob. Realtors Chemother 1990, 34, 1061C1067. [PMC free of charge content] [PubMed] [Google Scholar] 22. Stuyver LJ; Lostia S; Adams M; Mathew J; Pai BS; Grier J; Tharnish PM; Choi Y; Chong Y; Choo H; Chu CK; Otto MJ; Schinazi RF Antiviral actions and mobile toxicities of improved 2,3-dideoxy-2,3-didehydrocytidine analogues. Antimicrob. Realtors Chemother 2002, 46, 3854C3860. [PMC free of charge content] [PubMed] [Google Scholar] 23. Burgess K; Make D Syntheses of nucleoside triphosphates. Chem. Rev 2000, 100, 2047C2060. [PubMed] [Google Scholar] 24. a) Sluis-Cremer N; Sheen C-W; Zelina S; Argoti Torres PS; Parikh UM; Mellors JW Molecular system where the K70E mutation in individual immunodeficiency trojan type 1 invert transcriptase confers level of resistance to nucleoside invert transcriptase inhibitors. Antimicrob. Realtors Chemother 2007, 51, 48C53 [PMC free of charge content] [PubMed] [Google Scholar]b) Parikh UM; Zelina S; Sluis-Cremer N; Mellors JW Molecular systems of bidirectional antagonism between K65R and thymidine analog mutations in HIV-1 invert transcriptase. Helps 2007, 21, 1405C1414 [PubMed] [Google Scholar]c) Sluis-Cremer N; Arion D; Parikh U; Koontz D; Schinazi RF; Mellors JW; Parniak MA Enzyme catalysis and legislation. J. Biol. Chem 2005, 280, 29047C29052. [PubMed] [Google Scholar] 25. Wildtype (WT) HIV-1 (LAI) change transcriptase (RT) was purified as defined previously. The proteins concentration from the purified enzyme was driven spectrophotometrically at 280 nm using an extinction coefficient ( em ? /em 280) of 260450 M?1 cm?1, and by Bradford proteins assays (Sigma-Aldrich, St. Louis, MO, USA). AZT-TP was bought from TriLink Biotechnologies, Inc (NORTH PARK, CA, USA), dNTPs had been obtained from GE Health care (Piscataway, NJ, USA), and [ em /em -32P] ATP was extracted from PerkinElmer Lifestyle Sciences (Boston, MA, USA). DNA oligonucleotides had been synthesized by IDT (Coralville, IA,.