Nucleotide dimers suppress HIV expression in vitro.
A series of nucleotide homo- and heterodimers [3'-azido-3'-deoxythymidilyl-(5',5')-2',3'-di-deoxy-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'-thymid ilic 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.
Busso
M
M
Department of Dermatology, Mount Sinai Medical Center, Miami Beach, FL 33140.
Mian
A M
AM
Hahn
E F
EF
Resnick
L
L
D000998:Antiviral Agents; D002460:Cell Line; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D006678:HIV / Q000187:drug effects* / Q000502:physiology; D015488:HIV Antigens; D008826:Microbial Sensitivity Tests; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine / Q000031:analogs & derivatives / Q000494:pharmacology
D000998:Antiviral Agents; D015226:Dinucleoside Phosphates; D015488:HIV Antigens; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine