RESUMO
Several derivatives of 1-[(2-hydroxyethoxy)methyl]-6-(phenylthio)thymine (HEPT) were examined for their inhibitory effects on the replication of human immunodeficiency virus type 1 (HIV-1) in MT-4 cells in the presence of various concentrations (10-50%) of human serum (HS). Although all HEPT derivatives proved to be highly potent inhibitors of HIV-1 in the presence of 10% fetal bovine serum, some of them were less inhibitory to HIV-1 replication in the presence of HS. The HEPT derivatives were found to be highly bound to HS proteins. Both the anti-HIV-1 activity and HS protein binding of the compounds appeared to be related to their lipophilicity.
Assuntos
Acetilcisteína/análogos & derivados , Antivirais/farmacologia , Proteínas Sanguíneas/metabolismo , HIV-1/efeitos dos fármacos , Timina/análogos & derivados , Acetilcisteína/química , Acetilcisteína/metabolismo , Acetilcisteína/farmacologia , Sangue , Linhagem Celular , Ligação Proteica , Timina/metabolismo , Timina/farmacologia , Replicação Viral/efeitos dos fármacosRESUMO
The 4.4 kb SphI DNA fragment (GSH1) that complements the gamma-glutamylcysteine synthetase-deficient mutation (gsh1) of Saccharomyces cerevisiae YH1 was cloned into vector plasmid YEp24. Gene disruption of the cloned fragment confirmed that this segment was the same gene as gsh1. Mutant strain YH1 with this plasmid not only restored gamma-glutamylcysteine synthetase (GSH-I) activity but the glutathione content and the growth rate. DNA sequence analysis of the SphI fragment showed that the GSH1 structural gene contained 2034 bp and predicted a polypeptide of 678 amino acids. The deduced amino acid sequence had about a 45% homology to that of rat kidney GSH-I, but a very low homology (about 26%) to that of Escherichia coli GSH-I. Northern analysis showed that GSH1 had been transcribed into an approximately 2.7 kb mRNA fragment. Southern analysis showed that GSH1 mapped at chromosome X.
