Gene transfection activities of amphiphilic steroid-polyamine conjugates.
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.
Fujiwara
T
T
Faculty of Pharmaceutical Sciences, Nagoya City University, Tanabe-dori, Mizuho-ku, 467-8603, Nagoya, Japan.
Hasegawa
S
S
Hirashima
N
N
Nakanishi
M
M
Ohwada
T
T
D016475:3T3 Cells; D000818:Animals; D019556:COS Cells; D002776:Cholestanes / Q000737:chemistry; D018014:Gene Transfer Techniques; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D011073:Polyamines / Q000737:chemistry*; D013256:Steroids / Q000737:chemistry*; D013501:Surface-Active Agents
D002776:Cholestanes; D011073:Polyamines; D013256:Steroids; D013501:Surface-Active Agents