Synthesis of Serine/Alanine Conjugated 3′,5′-TpT
Bioorganic Phosphorus Chemistry Laboratory, Department of Chemistry, School of Life Science and Engineering, Tsinghua University, Beijing, P.R. China.Nucleosides Nucleotides & Nucleic Acids (Impact Factor: 1.02). 02/2003; 22(1):63-9. DOI: 10.1081/NCN-120018623
Serine and alanine phosphoramidates conjugates of 3',5'-TpT 4, 5 were synthesized. The corresponding serine phosphoamidate possesses some unique properties due to the presence of the side chain hydroxyl group.
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ABSTRACT: A new acyclic nucleoside phosphonate (13) containing an adenine moiety was synthesized, which acted as an excellent inhibitor of calf mucosal adenosine deaminase. This inhibitory property allows it to exert great synergistic effect on certain antiviral agents (e.g., ara-A, 37). Phosphonate 13 was not phosphorylated by the bovine brain guanylate kinase nor by 5-phosphoribosyl 1-pyrophosphate synthetase. Syntheses of biologically active nucleotide phosphonate 40 and its phosphonoamidate derivative 42 were accomplished, which showed remarkable activity against herpes viruses and exhibited low host cell toxicity. 3'-Azido-nucleoside phosphonate 20 and 3'-fluoronucleoside phosphonate 32, as well as the corresponding dinucleotide analogs 47 and 48, and their respective phosphonoamidates 53-56 were also synthesized as new compounds, among which phosphonoamidates 53-56 showed potent activity against human immunodeficiency virus. Phosphonoamidates 55 and 56 bearing a methyl D-alaninate moiety exhibited less cellular toxicity than 53 and 54 bearing a methyl L-alaninate moiety. Nucleotide phosphonate 40 as well as dinucleotide phosphonates 47 and 48 were found susceptible to degradation by phosphodiesterases. Their respective phosphonoamidates 42 and 53-56, however, were completely resistant to snake venom and spleen enzymes.Journal of Medicinal Chemistry 12/1995; 38(23):4648-59. DOI:10.1021/jm00023a004 · 5.45 Impact Factor
- Rapid Communications in Mass Spectrometry 10/2002; 16(20):1997-2002. DOI:10.1002/rcm.803 · 2.25 Impact Factor
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ABSTRACT: The decomposition pathways and kinetics in various biological media and the in vitro anti-HIV-1 and anti-HIV-2 activities of four derivatives of the 5'-mononucleotide of isoddA incorporating carboxylate esterase-labile transient phosphate protecting groups are reported and compared: namely, two mononucleoside aryl phosphoramidate derivatives 1a,b and two mononucleoside phosphotriester derivatives incorporating two S-acyl-2-thioethyl groups 2a,b. All four compounds show better antiviral activity, compared to the parent nucleoside analog isoddA. The results highlight that both types of compounds act as pronucleotides, i.e. they exert their antiviral effect via intracellular delivery of the 5'-mononucleotide of isoddA. The results may give insights for the design of new more efficient pronucleotides.Journal of Medicinal Chemistry 06/1996; 39(10):1981-90. DOI:10.1021/jm9507338 · 5.45 Impact Factor
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