Nucleotide Dimers Suppress HIV Expression In Vitro
- 1 January 1988
- journal article
- research article
- Published by Mary Ann Liebert Inc in AIDS Research and Human Retroviruses
- Vol. 4 (6), 449-455
- https://doi.org/10.1089/aid.1988.4.449
Abstract
A series of nucleotide homo- and heterodimers [3''-azido-3''-deoxythymidilyl-(5'',5'')-2'',3''-dideoxy-5'' adenylic acid (AZT-P-ddA), 3''-azido-3''-deoxythymidilyl-(5'',5'')-2'',3''-dideoxy;-5''-adenylic acid, 2-cyanoethyl ester [AZT-P(CyE)-ddA], 3''-azido-3''-deoxythymidilyl-(5'',5'')-2'',3''-dideoxy-5''-inosinic acid (AZT-P-ddI), and 3''-azido-3''deoxythymidilyl-(5'',5'')-3''-azido-3''-deoxy-5''-thymidilic acid (AZT-P-AZT)] were synthesized and compared with respect to their anti-HIV and cytotoxic properties to their component monomers in vitro. MT-2 cells were infected with HIV (TM) followed by the addition of drug. The dimers and their respective monomers inhibited HIV-induced syncytia formation, reverse transcriptase production, and the expression of HIV p24 antigen. However, on an equimolar basis, greater anti-HIV potency and enhanced cytotherapeutic indices were observed with the heterodimers when compared with their monomers. Nucleotide dimers, such as AZT-P-ddA, should be actively considered for further evaluation as anti-HIV agents.This publication has 15 references indexed in Scilit:
- PHASE I STUDIES OF 2',3'-DIDEOXYCYTIDINE IN SEVERE HUMAN IMMUNODEFICIENCY VIRUS INFECTION AS A SINGLE AGENT AND ALTERNATING WITH ZIDOVUDINE (AZT)The Lancet, 1988
- Ribavirin antagonizes inhibitory effects of pyrimidine 2',3'-dideoxynucleosides but enhances inhibitory effects of purine 2',3'-dideoxynucleosides on replication of human immunodeficiency virus in vitroAntimicrobial Agents and Chemotherapy, 1987
- The Efficacy of Azidothymidine (AZT) in the Treatment of Patients with AIDS and AIDS-Related ComplexNew England Journal of Medicine, 1987
- Long-term inhibition of human T-lymphotropic virus type III/lymphadenopathy-associated virus (human immunodeficiency virus) DNA synthesis and RNA expression in T cells protected by 2',3'-dideoxynucleosides in vitro.Proceedings of the National Academy of Sciences, 1987
- In Vitro Suppression of HTLV-III/LAV Infectivity by a Combination of Acyclovir and SuraminThe Journal of Infectious Diseases, 1986
- Phosphorylation of 3'-azido-3'-deoxythymidine and selective interaction of the 5'-triphosphate with human immunodeficiency virus reverse transcriptase.Proceedings of the National Academy of Sciences, 1986
- Inhibition of the in vitro infectivity and cytopathic effect of human T-lymphotrophic virus type III/lymphadenopathy-associated virus (HTLV-III/LAV) by 2',3'-dideoxynucleosides.Proceedings of the National Academy of Sciences, 1986
- ADMINISTRATION OF 3'-AZIDO-3'-DEOXYTHYMIDINE, AN INHIBITOR OF HTLV-III/LAV REPLICATION, TO PATIENTS WITH AIDS OR AIDS-RELATED COMPLEXThe Lancet, 1986
- Frequent Detection and Isolation of Cytopathic Retroviruses (HTLV-III) from Patients with AIDS and at Risk for AIDSScience, 1984
- 2-Cyanoethyl Phosphate and its Use in the Synthesis of Phosphate Esters1Journal of the American Chemical Society, 1961