Modulation of viral Internal Ribosome Entry Segments (IRES)
Lead Research Organisation:
University of Nottingham
Department Name: Sch of Pharmacy
Abstract
Abstracts are not currently available in GtR for all funded research. This is normally because the abstract was not required at the time of proposal submission, but may be because it included sensitive information such as personal details.
| 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 |