Synthesis and evaluation of new phosphonolipid compounds for gene delivery.
The preparation of a series of novel water soluble cationic lipid derivatives possessing phosphonate ester groups linked to the para-position of N-methyl pyridinium moieties and bearing either identical or different alkyl chains is reported. The obtained phospholipids were tested for transfection efficiency into three different mammalian cell lines alone and in conjunction with diphytanoylphosphatidylethanolamine (DiPPE) or dioleylphosphatidylethanolamine (DOPE), using an assay adapted for 96-well microplates based on the detection of a colorimetric change caused by the production of a chromogen induced by expressed secreted human placental alkaline phosphatase. In our conditions, the highest transfection activities of cells HEK293 and hard-to-transfect cell lines B16 and CHO were achieved with a 4-phosphonobutylpyridinium compound used at 1:5, 1:10 or 3:6 DNA/lipid ratio bearing two myristyl chains in the presence of the fusogenic helper lipid DiPPE.
Dal-Maso
Angélique Durand
AD
Laboratoire de Synthèse et Physico-Chimie de Molécules d'Intérêt Biologique, Groupe de Chimie Organique Biologique, UMR/CNRS 5068, Université Paul Sabatier, 118 route de Narbonne, 31062 Toulouse cedex 9, France.
Dellacasagrande
Jérôme
J
Legendre
Frédéric
F
Tiraby
Gérard
G
Blonski
Casimir
C
Hoffmann
Pascal
P
D000478:Alkylation; D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D018014:Gene Transfer Techniques; D006801:Humans; D008745:Methylation; D051379:Mice; D015394:Molecular Structure; D010743:Phospholipids / Q000138:chemical synthesis* / Q000737:chemistry; D011725:Pyridines / Q000737:chemistry; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry; D019076:Transgenes / Q000235:genetics
D010743:Phospholipids; D011725:Pyridines; D011726:Pyridinium Compounds; C028299:phosphonolipids; C023666:pyridine