title: Design, synthesis, and evaluation of enhanced DNA binding new lipopolythioureas.
abstract: 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 alpha(v)beta(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.
authors.affiliation: Inserm, U640, Paris, F-75006 France.
authors.forename: Jeanne
authors.initials: J
authors.lastname: Leblond
authors.forename: Nathalie
authors.initials: N
authors.lastname: Mignet
authors.forename: Lucie
authors.initials: L
authors.lastname: Leseurre
authors.forename: Céline
authors.initials: C
authors.lastname: Largeau
authors.forename: Michel
authors.initials: M
authors.lastname: Bessodes
authors.forename: Daniel
authors.initials: D
authors.lastname: Scherman
authors.forename: Jean
authors.initials: J
authors.lastname: Herscovici
mesh_terms: D000818:Animals; D002460:Cell Line; D004247:DNA / Q000378:metabolism*; D042783:Endothelial Cells / Q000166:cytology / Q000378:metabolism; D018014:Gene Transfer Techniques; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D051379:Mice; D015394:Molecular Structure; D009842:Oligopeptides / Q000378:metabolism; D010316:Particle Size; D013890:Thiourea / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D014162:Transfection / Q000379:methods
chemical_list: D008081:Liposomes; D009842:Oligopeptides; C047981:arginyl-glycyl-aspartic acid; D004247:DNA; D013890:Thiourea