Modulation of viral Internal Ribosome Entry Segments (IRES)
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Pharmacy
Abstract
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Title | Synthetic methods and new 1-phenylethyl-3-pyrimidineguanidines |
Description | We developed a convergent approach for the chemical synthesis of tripeptide-aminoanthraquinones (AAQ) conjugates. In brief, the cationic tripeptides, constructed by solid-phase chemistry on 1,3-diaminopropane chlorotrityl resin, were released by mild acidolysis to afford the partially protected peptides . The modified peptides were then selectively conjugated with the 6-bromohexanoyl-modified AAQ. The ten tripeptides-AAQ were obtained in good yields, but were of unacceptable aqueous solubility, even in the presence of DMSO; hence, we were unable to exploit these chemical tools to modulate HCV IRES function. Three 1-phenylethyl-3-pyrimidineguanidines (PPG) analogues, accessed via a 3-step synthetic strategy, were readily obtained and purified by reversed phase-HPLC. Novel PPG-AAQ conjugates were constructed. These are: (i) 3-(4-(2-(3-(4,6-dimethylpyrimidin-2-yl)guanidino)ethyl)phenoxy)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)propanamide; and (ii) 6-(4-(2-(3-(4,6-dimethylpyrimidin-2-yl)guanidino)ethyl)phenoxy)-N-(9,10-dioxo-9,10-dihydroanthracen-1-yl)hexanamide. |
Type Of Material | Technology assay or reagent |
Year Produced | 2007 |
Provided To Others? | Yes |
Impact | The impact is not obvious at the moment. |
Description | Dicistronic construct comprising T7 driven Renilla luciferase and HCV IRES driven firefly luciferase |
Organisation | University of Nottingham |
Department | School of Pharmacy |
Country | United Kingdom |
Sector | Academic/University |
PI Contribution | Design and synthesis of chemical reagents for IRES inhibition screens |
Collaborator Contribution | Provided research training and molecular tools to screen for HCV IRES inhibitors |
Impact | As part of the aims of the Discipline Hopping award, the PI obtained hands-on training in cellular and molecular biological techniques. |
Start Year | 2006 |