TACN-containing cationic lipids with ester bond: Preparation and application in gene delivery

Key Laboratory of Green Chemistry and Technology (Ministry of Education), College of Chemistry, West China Hospital, Sichuan University, Chengdu, People's Republic of China.
Bioorganic & medicinal chemistry letters (Impact Factor: 2.42). 12/2011; 21(23):7045-9. DOI: 10.1016/j.bmcl.2011.09.098
Source: PubMed


A series of novel cationic lipids based on 1,4,7-triazacyclononane (TACN) with different hydrophobic chains were synthesized via the formation of a biodegradable ester bond. These lipids were found to have good buffering capacity at the pH range of 5.0-6.5, which is similar to that of the acidic endosomal compartments. The liposomes formed from these lipids and DOPE could condense DNA into nanoparticles with proper sizes. In vitro experiments showed moderate to good gene transfection efficiency of the formed lipoplexes. The structure-activity relationships of this type of lipids were discussed.

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    ABSTRACT: Reaction of triazacyclononane (tacn) and aromatic aldehydes leads to aminal adducts, which exhibit only the exo configuration. In these aminal compounds, secondary amine function possesses a higher reactivity towards electrophilic reactants than the two nitrogen atoms linked to aminal carbon, giving rise to the specific derivatisation of tacn by different functionalised groups. Study of this behaviour also permits the access to a ditopic tacn-cyclam bicyclic polyamine. (c) 2012 Elsevier Ltd. All rights reserved.
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