Article Dans Une Revue Molecules Année : 2021

Phosphonodithioester–Amine Coupling as a Key Reaction Step for the Design of Cationic Amphiphiles Used for Gene Delivery

Résumé

A convergent synthesis of cationic amphiphilic compounds is reported here with the use of the phosphonodithioester-amine coupling (PAC) reaction. This versatile reaction occurs at room temperature without any catalyst, allowing binding of the lipid moiety to a polar head group. This strategy is illustrated with the use of two lipid units featuring either two oleyl chains or twobranched saturated lipid chains. The final cationic amphiphiles were evaluated as carriers for plasmid DNA delivery in four cell lines (A549, Calu3, CFBE and 16HBE) and were compared to standards (BSV36 and KLN47). These new amphiphilic derivatives, which were formulated with DOPE or DOPE-cholesterol as helper lipids, feature high transfection efficacies when associated with DOPE. The highest transfection efficacies were observed in the four cell lines at low charge ratios (CR = 0.7, 1 or 2). At these CRs, no toxic effects were detected. Altogether, this new synthesis scheme using the PAC reaction opens up new possibilities for investigating the effects of lipid or polar head groups on transfection efficacies.

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hal-05092141 , version 1 (02-06-2025)

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Montassar Khalil, Alexis Hocquigny, Mathieu Berchel, Tristan Montier, Paul-Alain Jaffrès. Phosphonodithioester–Amine Coupling as a Key Reaction Step for the Design of Cationic Amphiphiles Used for Gene Delivery. Molecules, 2021, 26 (24), pp.7507. ⟨10.3390/molecules26247507⟩. ⟨hal-05092141⟩
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