Design, Synthesis, and Evaluation of Enhanced DNA Binding New Lipopolythioureas

Jeanne Leblond (1) , Nathalie Mignet (2) , Lucie Leseurre (1) , Celine Largeau (1) , Michel Bessodes (3) , Daniel Scherman (1) , Jean Herscovici (1)

1 UPCG - UMR_S 640/UMR 8151 - Unité de Pharmacologie Chimique et Génétique
2 UTCBS - UM 4 (UMR 8258 / U1022) - Unité de Technologies Chimiques et Biologiques pour la Santé
3 UPCGI - UMR 8151 / UMR_S 1022 - Unité de pharmacologie chimique et génétique et d'imagerie

Nonviral gene delivery is limited to a large extent by the cationic nature of most of the chemical vector. We have shown that lipopolythioureas interact with DNA. However, lipopolythioureas were not very efficient at transfecting cells, probably due to reduced interaction between the noncationic synthetic lipid and the cell membrane. Here, we report that liposomes made from a new thiourea lipid, DPPC, and a lipid bearing an RGD ligand allowed very efficient entry of the lipopolythioureas into integrin R v 3 expressing cells. In addition, we show that a stable interaction between DNA and lipopolythiourea could be obtain with two thiourea groups. Moreover, the addition of a hydrophilic terminus improves the formulation of these new DNA binding agents.

Domaines: Chimie organique; Sciences pharmaceutiques

Jeanne Leblond, Nathalie Mignet, Lucie Leseurre, Celine Largeau, Michel Bessodes, et al.. Design, Synthesis, and Evaluation of Enhanced DNA Binding New Lipopolythioureas. Bioconjugate Chemistry, inPress, ⟨10.1021/bc060110g⟩. ⟨hal-02512562⟩