During my M.S. thesis work I was involved in a multistep synthesis of solid support bearing a modified nucleoside for automated synthesis of siRNAs. First, I developed a three-step synthesis of protected 5'-amino uridine from uridine. Next I prepared the 3'-succinate of 5'-amino uridine in a one-pot two-step synthesis and attached it to a solid support via a succinamide linker. I had analyzed and characterized all new compounds using NMR techniques. Others in our laboratory used this solid support for synthesis of amide-modified siRNAs. We anticipate that the amide linkages will facilitate crossing the cellular membrane and improve nuclease resistance, biodistribution and pharmacokinetics of modified siRNAs.

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