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The solid-phase synthesis of a library of arginine-containing lipid transfection agents on high-loading beads is described. The transfection activity of the cationic lipids was determined using compound cleaved from single beads (single-bead screening) and showed, in some cases, comparable or higher DNA transfection activities as compared to commercially available reagents. Lipids with one arginine headgroup and a cholesterol tail were found to be the most active, even though their DNA binding strength (retardation assays) was relatively weak. Single-bead screening of transfection activity facilitates the rapid analysis of libraries of transfection reagents and will allow the rapid optimization of gene delivery into cells, both in culture and in vivo.

Original publication




Journal article


Journal of combinatorial chemistry

Publication Date





753 - 760


Department of Chemistry, University of Southampton, Southampton SO17 1BJ, U.K.


Cell Line, Humans, Cations, Guanidine, Lipids, Arginine, Combinatorial Chemistry Techniques, Transfection, Microspheres, Cell Survival