Abstract
The cytotoxicity of a polycationic gene delivery system is critical for overall gene transfer efficency. Cells targeted for transfection must be able to support transcription and translation following gene delivery if treatment is to be successful. Cumulative cellular exposure time is one factor that mediates the cytotoxicity of polycations. Therefore, we hypothesized that hydrolytically degradable polycations, such as polyesters based on amino acids, could serve to reduce the cytotoxicity of polycationic gene delivery systems. In this paper, optimization of the low-temperature dicyclohexylcarbodiimide/(dimethylamino)pyridine (DCC/DMAP)-activated polycondensation of N-carbobenzyloxy-4-hydroxy-l-proline (CBZ-4-hydroxy-l-proline) to ultimately yield poly(4-hydroxy-l-proline ester) and the resulting polymer's interaction with plasmid DNA is reported. The optimized polycondensation of CBZ-4-hydroxy-l-proline resulted in a polymer with Mw = 7880. Deprotection of the CBZ group was afforded by palladium on activ...
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