Polycationic diblock and random polyethylene glycol- or tris(hydroxymethyl)methyl-grafted (co)telomers for gene transfer: synthesis and evaluation of their in vitro transfection efficiency.
We report on the synthesis of a series of polycationic telomers, polycationic diblock and random polyethylene glycol (PEG)-grafted (co)telomers, and polycationic random tris(hydroxymethyl)methyl (THM) cotelomers, and on their in vitro gene transfer capability. These compounds were obtained by a telomerization process of various amino-, tetraethylene glycol-, or THM-acrylamide taxogens with thiols which might derive from PEG2000. For N/P ratios [N is the number of (co)telomer amine equivalents; P is the number of DNA phosphate equivalents] from 0.8 to 10, these (co)telomers condensed DNA, forming (co)teloplexes with mean sizes in the 85-330 nm range, even for an N/P ratio of 0.8 or 1.25. Some structure-transfection efficiency relationships were established. Among the new polycationic derivatives that were synthesized and investigated for their transfection efficiency, the (i)Bu-[NH](75) telomers and the diblock polyethylene glycol-conjugated PEG2000-[NH](n) telomers are very promising candidates for gene transfer purposes.
Le Bon
Bertrand
B
Laboratoire de Chimie Bioorganique, UMR 6001 CNRS, Université de Nice Sophia-Antipolis, Faculté des Sciences, 06108 Nice Cédex 2, France.
Van Craynest
Nathalie
N
Boussif
Otmane
O
Vierling
Pierre
P
D006801:Humans; D008027:Light; D015394:Molecular Structure; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols / Q000737:chemistry*; D012542:Scattering, Radiation; D014162:Transfection / Q000379:methods*; D014407:Tumor Cells, Cultured
D011073:Polyamines; D000071228:Polyelectrolytes; D011092:Polyethylene Glycols