Abstract
The design and evaluation of a novel potent class of DNA delivery agents based on steroid–polyamine conjugates bearing a flexible linker are reported. The hydrophobic regions are based on steroids, i.e. chlolestane and lithocholic acid motifs. The linker, which couples a hydrophobic steroid and a hydrophilic polyamine, in this study can be regarded as a two-atom extension of the conventional carbamate linker. We found that the gene transfection activity of the steroid–polyamine conjugates is influenced by the polyamine chain length and steroid structure. Molecular modeling of the relevant amphiphilic molecules revealed low-energy structures in which the polyamine chains are folded rather than stretched. This work suggests a significant effect of space-filling, i.e. the shape and orientation of the hydrophilic and hydrophobic regions, upon the efficiency of gene transfection.
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More From: Biochimica et Biophysica Acta (BBA) - Biomembranes
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