Journal
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
Volume 19, Issue 1, Pages 100-103Publisher
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2008.11.009
Keywords
Lipoplex; Cholesterol; Cyclen; DNA; RNA; Transfection; Piperazine
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Funding
- European Union [LSHB-CT-2004-005276]
- CANSA
- South African National Research Foundation [GUN 68339, 65495, 2053652]
- ESASTAP
- South African Poliomyelitis Research Foundation
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To advance the use of cationic lipids for non-viral nucleic acid vector formulation, a panel of novel nitrogen heterocycle cholesteryl derivatives containing a biodegradable carbamate linker was synthesised. Optimally acting piperazine and cyclen compounds had nucleic acid-binding and lipoplex nanoparticle formation properties that were suitable for their use as non-viral vectors. It was found that the lipoplexes formed were capable of efficient non-toxic nucleic acid delivery to cells in culture. The chemical structure of individual cationic lipids, which is likely to influence lipoplex formation, affected efficiency of DNA or RNA transfection. The results indicated that the cyclen containing compound possessing two cholesteryl moieties resulted in efficient siRNA-mediated target gene silencing but was a poor reagent for DNA transfection. (C) 2008 Elsevier Ltd. All rights reserved.
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