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.