ORGN 164 |
| Internucleoside amides as hydrophobic non-ionic backbone modifications of RNA may improve the chemical and enzymatic stabilities, cellular uptake, biodistribution and pharmacokinetics of small interfering RNAs (siRNAs). This presentation discusses our synthetic and biophysical studies of amide modified RNA. Specifically, we have developed syntheses of 3'-aminomethyl (1) and 5'-carboxy (2) nucleosides from D-glucose. Coupling of monomers 1 and 2 produced the internucleoside amide linkage, which may be incorporated at any desired position of the target RNA. Preliminary biophysical data showed that amide modifications did not disturb the A-type RNA duplex formation and were surprisingly good mimics of the phosphodiester linkages of RNA. If amides are accepted by the protein machinery of RNA interference, such modifications may substantially improve properties of siRNAs and lead to the development of novel therapeutic agents.
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Total Synthesis, Materials, Devices and Switches, Molecular Recognition and Self-Assembly, Biologically-Related Molecules and Processes
8:00 PM-10:00 PM, Sunday, August 19, 2007 BCEC -- Exhibit Hall - B2, Poster
Sci-Mix
Division of Organic Chemistry |
