Synthesis and properties of double-stranded RNA-bindable oligodiaminogalactose derivatives conjugated with vitamin E.
RNA interference (RNAi) is a gene-regulating system that is controlled by external short interfering RNAs (siRNAs). Sequence selective gene silencing by siRNA shows promise in clinical research. However, there have been few efficient methods for delivering siRNAs to target cells. In this study, we propose a novel type of RNA duplex-bindable molecule with an oligodiaminosaccharide structure. These 2,6-diamino-2,6-dideoxy-(1-4)-β-D-galactopyranose oligomers (oligodiaminogalactoses; ODAGals) conjugated with α-tocopherol (vitamin E; VE) or a VE analog were designed as novel siRNA-bindable molecules that can be utilized to deliver RNAi drugs to the liver. Among these compounds, the VE analog-bound ODAGal was suggested to bind to RNA duplexes without inhibiting RNAi activity.
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan.
Rintaro
R
Iwata
Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Kazutaka
K
Nishina
Department of Neurology and Neurological Science, Graduate School, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Takanori
T
Yokota
Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan; Department of Medical Genome Sciences, Graduate School of Frontier Sciences, The University of Tokyo, Bioscience Building 702, 5-1-5 Kashiwanoha, Kashiwa, Chiba 277-8562, Japan. Electronic address: twada@rs.tus.ac.jp.
Takeshi
T
Wada
D000818:Animals; D045744:Cell Line, Tumor; D005690:Galactose / Q000737:chemistry*; D006001:Glycoconjugates / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism; D009691:Nucleic Acid Denaturation; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000737:chemistry / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D051381:Rats; D014466:Ultraviolet Rays; D014810:Vitamin E / Q000737:chemistry*
D006001:Glycoconjugates; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D014810:Vitamin E; D005690:Galactose
Drug delivery system; Oligodiaminogalactose; RNA duplex; RNA interference; Vitamin E