Polycationic telomers and cotelomers for gene transfer: synthesis and evaluation of their an vitro transfection efficiency.

We report on the synthesis of a series of lipopolyamine telomers, I(Asp)-14,n(A)(NH), I(His)-18,n(A)(NH), I-18,n(B)(NMe), Gal-n(A)(NH)], and random cotelomers, I-18,n(A)(NH)-n(B)(NMe) and I-18,n(A)(NH)-n(C)(OH)], and on their in vitro gene transfer capability. They were obtained by a telomerization process of various amino-acrylamide taxogens with various lipophilic thiol telogens which might also contain an aspartic or a histidine residue or with a thiogalactosyle derivative. For N/P ratios (N = number of (co)telomer amine equivalents, P = number of DNA phosphates) from 0.8 to 10, these polyamine (co)telomers condensed DNA, with or without the use of DOPE, forming (co)teloplexes of mean sizes less than 200 nm, except for N/P 1.25 for which precipitates were observed. Some trends, structure-transfection efficiency relationships, were established. Thus, aspartic-containing telomers were found to lead to efficient formulations for plasmid delivery to A549 cells and for N/P ratios from 1.25 to 5.