CARB 65 |
| Discovery of RNA interference has reinvigorated interest in chemical modifications of RNA. Our work is focused on the development of novel nonionic analogues of RNA having formacetal and amide linkages. We hypothesize that the reduced negative charge and hydrophobic nature of such modifications will increase the enzymatic stability may have the potential to optimize potency, cellular uptake, and pharmacokinetics of small interfering RNAs. Amide modifications in RNA can be prepared using relatively straightforward peptide type couplings. The synthetic challenge is the preparation of the nucleoside-derived amino acids 1 and 2 (Figure), which are difficult targets for chemical manipulations because of high density and reactivity of functional groups. This presentation will discuss synthesis and biophysical properties of amide-modified RNA. The focus will be on asymmetric de-novo routes for synthesis of C-homologated carbohydrates, modified nucleosides, and amide-modified RNA. Novel syntheses that avoid extensive protecting group manipulations and sensitive intermediates will be presented.
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Oligonucleotides and Therapeutic Applications
9:00 AM-11:50 AM, Wednesday, 29 March 2006 Georgia World Congress Center -- B409, Oral
Division of Carbohydrate Chemistry |
