Solid phase synthesis of novel asymmetric hydrophilic head cholesterol-based cationic lipids with potential DNA delivery.

Abstract

Twenty-four asymmetric divalent head group cholesterol-based cationic lipids were designed and synthesized by parallel solid phase chemistry. These asymmetric head groups composed of amino functionality together with trimethylamino, di(2-hydroxyethyl)amino or guanidinyl groups. Spacers between cationic heads and linker were both equal and unequal in length. These lipids were subjected to evaluation for DNA binding affinities by gel retardation assay and were screened for their transfection efficiency on HEK293 cells. Cationic lipids with equal chain length exhibited high transfection efficiency when polar part contained asymmetric polar heads. In contrast, lipids with unequal chain length exhibited high transfection efficiency when polar part contained symmetric heads. According to the optimal formulation, seven lipids exhibited higher transfection efficiency than the commercially available transfection agents, Effectene, DOTAP and DC-Chol, to deliver DNA into PC3 human prostate adenocarcinoma cells. 3beta-[N-(N'-Guanidinyl)-2'-aminoethyl)-N-(2-aminoethyl)carbamoyl] cholesterol (5) bearing amino and guanidinyl polar heads exhibited highest transfection efficiency with minimal toxicity. The morphology of active liposomes was observed by transmission electron microscopy (TEM) and size of liposomes were around 200-700 nm.

• Authors: Widchaya Radchatawedchakoon, Ramida Watanapokasin, Aungkana Krajarng, Boon-ek Yingyongnarongkul
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 18 Issue 1 Pg. 330-42 (Jan 01 2010) ISSN: 1464-3391 [Electronic] England
• PMID: 19932970 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright (c) 2009 Elsevier Ltd. All rights reserved.

Chemical References

• 1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine
• Cations
• Lipids
• Liposomes
• Phosphatidylethanolamines
• DNA
• Cholesterol

Topics

• Binding Sites
• Cations (chemical synthesis, chemistry)
• Cell Line
• Cell Line, Tumor
• Cholesterol (chemical synthesis, chemistry)
• DNA (administration & dosage, chemistry)
• Humans
• Lipids (chemical synthesis, chemistry)
• Liposomes (chemistry)
• Phosphatidylethanolamines (chemical synthesis, chemistry)
• Serum (chemistry)
• Transfection