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ID: ALA3393030

Journal: Bioorg Med Chem Lett

Title: Synthesis and properties of vitamin E analog-conjugated neomycin for delivery of RNAi drugs to liver cells.

Authors: Iwata R, Nakayama F, Hirochi S, Sato K, Piao W, Nishina K, Yokota T, Wada T.

Abstract: RNA interference (RNAi) is a promising tool to regulate gene expression by external double stranded RNAs (dsRNAs) such as siRNAs. As an efficient method to deliver siRNAs to liver cells, we propose a novel strategy using vitamin E (VE)-conjugated neomycin derivatives. With the aim of delivering RNAi-based drugs to liver cells, several tripod-type and prodrug-type neomycin derivatives were synthesized, all of which were thermodynamically stabilized RNA duplexes. The prodrug-type derivative 7 and the tripod-type derivative 10 were delivered to liver cancer cells and successfully induced RNAi activity. These results indicated the potential use of natural aminoglycosides as carriers of RNAi drugs.

CiteXplore: 25597008

DOI: 10.1016/j.bmcl.2014.12.079