Deoxythioguanosine triphosphate impairs HIV replication: a new mechanism for an old drug.
FASEB J
; 15(11): 1902-8, 2001 Sep.
Article
em En
| MEDLINE
| ID: mdl-11532970
ABSTRACT
Inhibition of HIV-1 reverse transcriptase (RT) and HIV protease are effective mechanisms for anti-retroviral agents, and the combined use of mechanistically different medications has markedly improved the treatment of HIV infected patients. The active metabolite of mercaptopurine and thioguanine (TG), deoxythioguanosine triphosphate, was shown to be incorporated into DNA by the polymerase function of HIV-1 RT and then to abrogate RNA cleavage by HIV-1 RNaseH. Treatment of human lymphocyte cultures with thioguanine produced substantial inhibition of HIV replication (IC(50)=0.035 microM, IC(95)=15.4 microM), with minimal toxicity to host lymphocytes (<10% at 15.4 microM TG, P<0.000005). Furthermore, low concentrations of TG and zidovudine were synergistic in inhibiting HIV replication in human lymphocytes (synergy volume=19 microM(2)%), without additive cytotoxicity to host lymphocytes. Thus, thiopurines are novel anti-retroviral agents that alter the DNA-RNA substrates for HIV RNaseH, thereby abrogating early stages of HIV replication.
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Base de dados:
MEDLINE
Assunto principal:
Tioguanina
/
Tionucleotídeos
/
Replicação Viral
/
HIV-1
/
Inibidores da Síntese de Ácido Nucleico
/
Fármacos Anti-HIV
/
Nucleotídeos de Desoxiguanina
/
Transcriptase Reversa do HIV
/
Mercaptopurina
Limite:
Humans
Idioma:
En
Revista:
FASEB J
Assunto da revista:
BIOLOGIA
/
FISIOLOGIA
Ano de publicação:
2001
Tipo de documento:
Article
País de afiliação:
Estados Unidos