AEGiS-06IAC: The selectivity of phosphonate analogues of nucleoside 5'-triphosphates towards reverse transcriptases.

6th International AIDS Conference

San Francisco, California, USA — June 20-23, 1990

The selectivity of phosphonate analogues of nucleoside 5'-triphosphates towards reverse transcriptases.

Int Conf AIDS 1990 Jun 20-23; 6:331 (abstract no. 1070)
Krayevsky AA, Tarussova NB, Rosovskaya TA, Atrazheva ED; The V.A. Engelhart Institute of Molecular Biology USSR Academy of Sciences, Moscow, USSR

OBJECTIVE: The terminator and substrate properties of AzT, dT and 2',3'-O-isopropylidene cytidine (IpC) 5'-triphosphate analogues modified in different position of phosphorus containing chain have been studied.

METHODS: The compounds were synthesized by the reaction of AzT and dT 5'-phosphate morpholidates as well as of AzT and IpC hydroxymethanephosphonic esters morpholidates with phosphonoacetic, dibrommomethane diphosphonic acids and pyrophosphate. We studied their ability to inhibit DNA synthesis catalyzed with the E.coli DNA polymerase I, Klenov fragment, rat liver DNA polymerase beta, calf thymus terminal deoxynucleotidyltransferase, reverse transcriptases (RT) of avian myeloblastosis virus and HIV-1.

RESULTS: We show the synthesized analogues to be more specific to RT than to other DNA polymerases. Some of them appear to be selective and effective inhibitors of the HIV-1 RT in vitro.

CONCLUSION: Phosphonate analogues of nucleoside 5'-triphosphate give the possibility to characterize peculiar properties of different viral RT.

Keywords: AEGIS, RNA-Directed DNA Polymerase, DNA-Directed DNA Polymerase, Myeloblastosis Virus, Avian, Nucleotides, DNA Polymerase I, Reverse Transcriptase Inhibitors, DNA Polymerase beta, Zidovudine, DNA Nucleotidylexotransferase, HIV-1, Terminator Regions (Genetics), DNA Replication, DNA Primers, Antiviral Agents, In Vitro, Rats, Animal, genetics, ICA6

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