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

被引：9

作者：

Iwata, Rintaro ^{[1
,3
]}

Nakayama, Futoshi ^{[2
]}

Hirochi, Sakie ^{[2
]}

Sato, Kazuki ^{[2
]}

Piao, Wenying ^{[3
,4
]}

Nishina, Kazutaka ^{[3
,4
]}

Yokota, Takanori ^{[3
,4
]}

Wadaa, Takeshi ^{[1
,2
,3
]}

机构：

[1] Tokyo Univ Sci, Fac Pharmaceut Sci, Noda, Chiba 2788510, Japan

[2] Univ Tokyo, Grad Sch Frontier Sci, Dept Med Genome Sci, Kashiwa, Chiba 2778562, Japan

[3] JST CREST, Chiyoda Ku, Tokyo 1020076, Japan

[4] Tokyo Med & Dent Univ, Grad Sch, Dept Neurol & Neurol Sci, Bunkyo Ku, Tokyo 1138519, Japan

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2015年 / 25卷 / 04期

关键词：

Neomycin B; RNA interference; Vitamin E; Drug delivery system; SIRNA DELIVERY; PROTEIN;

D O I：

10.1016/j.bmcl.2014.12.079

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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. (C) 2015 Published by Elsevier Ltd.

引用

页码：815 / 819

页数：5

共 14 条

[1] Aminoglycoside-derived cationic lipids as efficient vectors for gene transfection in vitro and in vivo
Belmont, P
Aissaoui, A
Hauchecorne, M
Oudrhiri, N
Petit, L
Vigneron, JP
Lehn, JM
Lehn, P
[J]. JOURNAL OF GENE MEDICINE, 2002, 4 (05) : 517 - 526
[2] Rapid diversity-oriented synthesis in microtiter plates for in situ screening of HIV protease inhibitors
Brik, A
Muldoon, J
Lin, YC
Elder, JH
Goodsell, DS
Olson, AJ
Fokin, VV
Sharpless, KB
Wong, CH
[J]. CHEMBIOCHEM, 2003, 4 (11) : 1246 - 1248
[3] Structure-based discovery of ligands targeted to the RNA double helix
Chen, Q
Shafer, RH
Kuntz, ID
[J]. BIOCHEMISTRY, 1997, 36 (38) : 11402 - 11407
[4] Self-assembled lamellar complexes of siRNA with lipidic aminoglycoside derivatives promote efficient siRNA delivery and interference
Desigaux, Lea
Sainlos, Matthieu
Lambert, Olivier
Chevre, Raphael
Letrou-Bonneval, Emilie
Vigneron, Jean-Pierre
Lehn, Pierre
Lehn, Jean-Marie
Pitard, Bruno
[J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2007, 104 (42) : 16534 - 16539
[5] Breaking down the barriers: siRNA delivery and endosome escape
Dominska, Monika
Dykxhoorn, Derek M.
[J]. JOURNAL OF CELL SCIENCE, 2010, 123 (08) : 1183 - 1189
[6] Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans
Fire, A
Xu, SQ
Montgomery, MK
Kostas, SA
Driver, SE
Mello, CC
[J]. NATURE, 1998, 391 (6669) : 806 - 811
[7] P-chiral oligonucleotides in biological recognition processes
Guga, Piotr
[J]. CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2007, 7 (07) : 695 - 713
[8] Affinity for alpha-tocopherol transfer protein as a determinant of the biological activities of vitamin E analogs
Hosomi, A
Arita, M
Sato, Y
Kiyose, C
Ueda, T
Igarashi, O
Arai, H
Inoue, K
[J]. FEBS LETTERS, 1997, 409 (01) : 105 - 108
[9] The molecular basis of vitamin E retention:: Structure of human α-tocopherol transfer protein
Meier, R
Tomizaki, T
Schulze-Briese, C
Baumann, U
Stocker, A
[J]. JOURNAL OF MOLECULAR BIOLOGY, 2003, 331 (03) : 725 - 734
[10] Paromomycin and neomycin B derived cationic lipids: Synthesis and transfection studies
Mevel, Mathieu
Sainlos, Matthieu
Chatin, Benoit
Oudrhiri, Noufissa
Hauchecorne, Michele
Lambert, Olivier
Vigneron, Jean-Pierre
Lehn, Pierre
Pitard, Bruno
Lehn, Jean-Marie
[J]. JOURNAL OF CONTROLLED RELEASE, 2012, 158 (03) : 461 - 469

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