Synthesis of 3β[L-lysinamide-carbamoyl] cholesterol derivatives by solid-phase method and characteristics of complexes with antisense oligodeoxynucleotides

In this report, we describe the synthesis of mono- and di-valent cationic 3 beta[L-Lysinamide-carbamoyl] cholesterol (K-Chol) derivatives by solid-phase peptide synthesis method and the characteristics of K-Chol/ antisense otigodeoxynucleotide (ODN) complexes. K-Chol was able to interact with antisense ODNs electrostatically and constructed nanometer-sized complexes of 50-100 nm in diameter. The formation of K-Chol/antisense ODN complexes was demonstrated by non-denaturing polyacrylamide gel electrophoresis assay and atomic force microscopy. The cell-associated radioactivity was measured to monitor the cellular uptake of the complexes containing radioactive antisense ODNs using HL 60 cells.