title: Lipopolycationic telomers for gene transfer: synthesis and evaluation of their in vitro transfection efficiency.
abstract: We report on the synthesis of a series of lipopolyamine telomers I-14,n, I-18,n, and II-18,n and on their in vitro gene-transfer capability. Their structure consists of a polyamine polar moiety, including n primary amine functions (from 1 to 70), connected to a hydrophobic moiety, including two hydrocarbon C14 or C18 chains, through a mercaptopropanoyl or mercaptoglyceryl unit and an amide or ether function. They were obtained by telomerization of N-[2-[(BOC)aminoethyl]]acrylamide with N,N-ditetradecyl- and N,N-dioctadecylpropanamide-3-thiol and rac-1,2-dioctadecyloxypropane-3-thiol, respectively, then BOC deprotection. For N/P ratios (N = number of telomer amine equivalents; P = number of DNA phosphates) from 0.8 to 10, these lipopolyamines condensed DNA, with or without the use of DOPE, forming lipopolyplexes or teloplexes of mean sizes less than 200 nm. Some trends, structure-activity and structure-toxicity relationships, were established to achieve both highest in vitro transfection levels and cell viability. Thus, DNA formulations based on telomers I-14,20 and I-18,20 and for N/P ratios lower than 5 led to the most efficient teloplex formulations for plasmid delivery to lung epithelial A549 cells.
authors.affiliation: Laboratoire de Chimie Bio-Organique, ESA 6001 CNRS, Université de Nice Sophia-Antipolis, Faculté des Sciences, 06108 Nice Cédex 2, France.
authors.forename: G
authors.initials: G
authors.lastname: Verderone
authors.lastname: Van Craynest N
authors.forename: O
authors.initials: O
authors.lastname: Boussif
authors.forename: C
authors.initials: C
authors.lastname: Santaella
authors.forename: R
authors.initials: R
authors.lastname: Bischoff
authors.forename: H V
authors.initials: HV
authors.lastname: Kolbe
authors.forename: P
authors.initials: P
authors.lastname: Vierling
mesh_terms: D002470:Cell Survival; D004587:Electrophoresis, Agar Gel; D018014:Gene Transfer Techniques; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008055:Lipids / Q000737:chemistry*; D008156:Luciferases / Q000235:genetics; D008168:Lung / Q000473:pathology; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010957:Plasmids; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry; D011108:Polymers; D013329:Structure-Activity Relationship; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D008055:Lipids; D010714:Phosphatidylethanolamines; D011073:Polyamines; D011108:Polymers; D008156:Luciferases