Seeking MRNA Methylation Inhibitors as Antiviral Agents
Metadata Field | Value | Language |
---|---|---|
dc.contributor.advisor | Schneller, Stewart | |
dc.contributor.advisor | Livant, Peter | en_US |
dc.contributor.advisor | Goodwin, Douglas | en_US |
dc.contributor.advisor | Gorden, Anne E. V. | en_US |
dc.contributor.author | Li, Weikuan | en_US |
dc.date.accessioned | 2009-02-23T15:56:21Z | |
dc.date.available | 2009-02-23T15:56:21Z | |
dc.date.issued | 2008-08-15 | en_US |
dc.identifier.uri | http://hdl.handle.net/10415/1540 | |
dc.description.abstract | Aristeromycin and neplanocin A are two examples of potent S-adenosylhomocysteine hydrolase inhibitors. As a consequence, they show significant broad-spectrum antiviral activity, however, their clinical potential is limited by toxicity, which is associated with phosphorylation at their 5'-hydroxyl groups. 5'-Noraristeromycin has been found to exhibit wide-spectrum antiviral activity with reduced toxicity due to its inability to form the corresponding nucleotide. To explore new antiviral agents retaining aristeromycin-based activity while reducing undesired toxicity, 5'-fluoro-5'-deoxyaristeromycin (1), 4'-fluoro-4'-deoxynoraristeromycin (2), 3,7-dideazaaristeromycin (3) and 3,7-dideazanoraristeromycin (4) were synthesized. Compounds 1 and 2 showed moderate activity against measles but were inactive in other antiviral assays. Compounds 3 and 4 exhibited no significant activity against all viruses tested. Another member of the adenosine (Ado) set is sinefungin (5), which is a naturally occurring analog of S-adenosyl-L-homocysteine (AdoHcy) or S-adenosylmethionine (AdoMet). The wide-spectrum biological activities (anti-fungal, anti-virus, anti-bacteria and anti-malarial) are associated with its inhibition of AdoMet dependent methyltransferases. The application of sinefungin is limited by its toxicity. A convenient synthesis of sinefungin and related compounds (6, 7 and 8) was developed. | en_US |
dc.language.iso | en_US | en_US |
dc.rights | EMBARGO_NOT_AUBURN | en_US |
dc.subject | Chemistry and Biochemistry | en_US |
dc.title | Seeking MRNA Methylation Inhibitors as Antiviral Agents | en_US |
dc.type | Dissertation | en_US |
dc.embargo.length | MONTHS_WITHHELD:6 | en_US |
dc.embargo.status | EMBARGOED | en_US |
dc.embargo.enddate | 2009-08-23 | en_US |