CARB 17 |
| The discovery of RNA interference has revitalized the potential of synthetic oligonucleotides in gene therapy. Chemical modifications may improve enzymatic stability, cellular uptake, biodistribution and pharmacokinetics of small interfering RNAs. The problem is to design a non-perturbing modification that would offer the benefits without encumbering the biological activity. Whereas the effect of modifications on the structure of nucleic acids has been thoroughly studied in many cases, the important interplay of chemistry and hydration has been largely overlooked. Herein, I present our recent studies on the effect of several hydrophobic modifications of sugar-phosphate backbone and heterocyclic nucleobases on the hydration of RNA using osmotic stress methodology. The most important finding was that hydrophobic modifications do not necessarily decrease the hydration of RNA. In several cases, correlation between the thermal stability and hydration of RNA's secondary structure was noticed. We hypothesize that successful modifications must mimic both structure and hydration of RNA. |
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Nucleic Acids as Drug Targets
8:00 AM-11:50 AM, Monday, August 20, 2007 BCEC -- 208, Oral
Division of Carbohydrate Chemistry |