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

摘要

We report on the synthesis of a series of lipopolyamine telomers,[I(Asp)-14,n_A(NH),I(His-18,nA(NH),I-18,nB(NMe),Gal-n_A(NH)],and random cotelomers,[I-18,nB(NMe) and I-18,nA(NH)-nc(OH)], and on their in vitro gene transfer capability.They were obtained by a telomerizationprocess of various amino-acrylamide taxogens with various lipophilic thiol telogens which might also contain an aspartic or a histidine residue or with a thiogalactosyle derivatiive.For N/P ratios 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 obseved.Some trends,structure-transfection efficiency relationships,were established.Thus,aspartic-containing trends,structure-transfection efficient formulations for plasmid delivery to A549 cells and for N/P ratios from 1.25 to 5.