A conformational mimetic approach for the synthesis of carbocyclic nucleosides as anti-HCV leads
Computer-aided approaches coupled with medicinal chemistry were used to explore novel carbocyclic nucleosides as potential anti-hepatitisC virus (HCV) agents. Conformational analyses were carried out on 6-amino-1H-pyrazolo[3,4-d]pyrimidine (6-APP)-based carbocyclic nucleoside analogues, which were considered as nucleoside mimetics to act as HCV RNA-dependent RNA polymerase (RdRp) inhibitors. Structural insight gained from the modeling studies revealed the molecular basis behind these nucleoside mimetics. The rationally chosen 6-APP analogues were prepared and evaluated for anti-HCV activity. RdRp SiteMap analysis revealed the presence of a hydrophobic cavity near C7 of the nucleosides; introduction of bulkier substituents at this position enhanced their activity. Herein we report the identification of an iodinated compound with an EC50 value of 6.6μM as a preliminary anti-HCV lead.
Real-time linear detection probes: sensitive 5'-minor groove binder-containing probes for PCR analysis
Oligonucleotide probes/conjugates are provided along with method for their use in assays to monitor amplification wherein the signal produced does not rely on 5′ nuclease digestion.
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(2008/06/13)
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