The synthesis of cholesterol-based cationic lipids with trimethylamine head and the effect of spacer structures on transfection efficiency

被引：18

作者：

Kim, Bieong-Kil ^{[1
]}

Bae, Yun-Ui ^{[2
]}

Doh, Kyung-Oh ^{[2
]}

Hwang, Guen-Bae ^{[1
]}

Lee, Sung-Hye ^{[2
]}

Kang, Hyungu ^{[1
]}

Seu, Young-Bae ^{[1
]}

机构：

[1] Kyungpook Natl Univ, Sch Life Sci & Biotechnol, Taegu 702701, South Korea

[2] Yeungnam Univ, Dept Physiol, Coll Med, Taegu 705717, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2011年 / 21卷 / 12期

关键词：

Cholesterol; Cationic liposome; Transfection; Gene transfer technique; GENE DELIVERY; ETHER LINKAGE; HEADGROUP; SKELETON; THERAPY; SYSTEMS; RISK;

D O I：

10.1016/j.bmcl.2011.04.071

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Five cholesterol-based cationic lipids were newly synthesized based on cholest-5-en-3 beta-oxyethane-N,N,N-trimethylammonium bromide (Chol-ETA) structure where the cholesterol backbone is linked to cationic head via various lengths of ether-linked carbon spacer. The transfection efficiency of these compounds was increased in order of three (Chol-PRO) < four (Chol-BTA) < two (Chol-ETA) methylene unit in their spacer, and was decreased by an addition of isomethyl group to Chol-PRO spacer. In case of the presence of multiple bonds in the spacer, it required the more cationic lipids in liposome formulation than single bond in the spacer to present similar transfection efficiency. Crown Copyright (C) 2011 Published by Elsevier Ltd. All rights reserved.

引用

页码：3734 / 3737

页数：4

共 16 条

[1] Effect of the headgroup variation on the gene transfer properties of cholesterol based cationic lipids possessing ether linkage [J].

Bajaj, Avinash ;

Mishra, Santosh K. ;

Kondaiah, Paturu ;

Bhattacharya, Santanu .

BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES, 2008, 1778 (05) :1222-1236

[2] Design, synthesis, and in vitro gene delivery efficacies of novel cholesterol-based gemini cationic lipids and their serum compatibility: A structure-activity investigation [J].

Bajaj, Avinash ;

Kondiah, Paturu ;

Bhattacharya, Santanu .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (10) :2432-2442

[3] Synthesis and transfection properties of novel non-toxic monocationic lipids. Variation of lipid anchor, spacer and head group structure [J].

Fichert, T ;

Regelin, A ;

Massing, U .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2000, 10 (08) :787-791

[4] Advantage of the ether linkage between the positive charge and the cholesteryl skeleton in cholesterol-based amphiphiles as vectors for gene delivery [J].

Ghosh, YK ;

Visweswariah, SS ;

Bhattacharya, S .

BIOCONJUGATE CHEMISTRY, 2002, 13 (02) :378-384

[5] Nature of linkage between the cationic headgroup and cholesteryl skeleton controls gene transfection efficiency [J].

Ghosh, YK ;

Visweswariah, SS ;

Bhattacharya, S .

FEBS LETTERS, 2000, 473 (03) :341-344

[6] Synthesis of novel cholesterol-based cationic lipids for gene delivery [J].

Kim, Bieong-Kil ;

Doh, Kyung-Oh ;

Nam, Joo Hyeung ;

Kang, Hyungu ;

Park, Jong-Gu ;

Moon, Ik-Jae ;

Seu, Young-Bae .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (11) :2986-2989

[7] Murine leukemia induced by retroviral gene marking [J].

Li, ZX ;

Düllmann, J ;

Schiedlmeier, B ;

Schmidt, M ;

von Kalle, C ;

Meyer, J ;

Forster, M ;

Stocking, C ;

Wahlers, A ;

Frank, O ;

Ostertag, W ;

Kühlcke, K ;

Eckert, HG ;

Fehse, B ;

Baum, C .

SCIENCE, 2002, 296 (5567) :497-497

[8] The cation-pi interaction [J].

Ma, JC ;

Dougherty, DA .

CHEMICAL REVIEWS, 1997, 97 (05) :1303-1324

[9] Gene therapy - What to do when clear success comes with an unclear risk? [J].

Marshall, E .

SCIENCE, 2002, 298 (5593) :510-511

[10] The problem with cationic liposome/micelle-based non-viral vector systems for gene therapy [J].

Miller, AD .

CURRENT MEDICINAL CHEMISTRY, 2003, 10 (14) :1195-1211

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