Cationic lipophosphoramidates with two disulfide motifs: synthesis, behaviour in reductive media and gene transfection activity.
Lipophosphoramidates have previously been identified as efficient vectors for gene delivery. The incorporation of functional groups that respond to a physiological stimulus is hypothesised to further improve the efficacy of this type of vector and eventually reduce its cytotoxicity. In the present work, we report the effects of the incorporation of two disulfide motifs into the hydrophobic domain, close to the phosphoramidate group. Three cationic vectors possessing such a red/ox sensitive function were synthesised. The capability of one of them (5b) to compact DNA is reported jointly with its ability to release that DNA in the presence of a reducing agent. Finally, compound 5b was tested as a vector for gene delivery into human cells in vitro and its cytotoxicity was also evaluated.
Université Européenne de Bretagne, Université de Brest, CEMCA, CNRS UMR 6521, SFR ScInBIoS, 6 Avenue Le Gorgeu, 29238 Brest, France.
Aurore
A
Fraix
Tony
T
Le Gall
Mathieu
M
Berchel
Caroline
C
Denis
Pierre
P
Lehn
Tristan
T
Montier
Paul-Alain
PA
Jaffrès
D000577:Amides / Q000737:chemistry* / Q000494:pharmacology; D002412:Cations / Q000737:chemistry; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004247:DNA / Q000737:chemistry / Q000235:genetics; D004220:Disulfides / Q000737:chemistry* / Q000494:pharmacology; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000737:chemistry* / Q000235:genetics / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D010084:Oxidation-Reduction; D010756:Phosphoric Acids / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000577:Amides; D002412:Cations; D004220:Disulfides; D010756:Phosphoric Acids; D004247:DNA; C011067:phosphoramidic acid