کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
1361306 | 981460 | 2012 | 5 صفحه PDF | دانلود رایگان |
![عکس صفحه اول مقاله: Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics Inhibition of hepatitis C virus NS5A by fluoro-olefin based γ-turn mimetics](/preview/png/1361306.png)
The HCV non-structural protein NS5A has been established as a viable target for the development of direct acting antiviral therapy. From computational modeling studies strong intra-molecular hydrogen bonds were found to be a common structural moiety within known NS5A inhibitors that have low pico-molar replicon potency. Efforts to reproduce these γ-turn-like substructures provided a novel NS5A inhibitor based on a fluoro-olefin isostere. This fluoro-olefin containing inhibitor exhibited picomolar activity (EC50 = 79 pM) against HCV genotype 1b replicon without measurable cytotoxicity. This level of activity is comparable to the natural peptide-based inhibitors currently under clinic evaluation, and demonstrates that a peptidomimetic approach can serve as a useful strategy to produce potent and structurally unique inhibitors of HCV NS5A.
Fluoro-olefin 2 was designed to mimic intramolecular hydrogen bonds in NS5A inhibitors and demonstrated pico-molar anti-HCV activity in vitro.Figure optionsDownload as PowerPoint slide
Journal: Bioorganic & Medicinal Chemistry Letters - Volume 22, Issue 8, 15 April 2012, Pages 2938–2942