Chemical modification enhances the inhibitory effect of regulatory subunit antisense oligodeoxynucleotide of cAMP-dependent protein kinase type I on cell proliferation

The analysis of the action of antisense oligodeoxynucleotide complementary to mRNA of the type I cAMP-dependent protein kinase regulatory subunit has revealed a stable inhibitory effect of the substance on Molt-4 leukemic cell proliferation. To enhance the efficiency of the oligodeoxynucleotide action, its molecule was subjected to terminal modifications. The hydrophobic radical-effected modification at the 5'-end was carried out at the last stage of automated synthesis using undecanol. At the 3'-end, the molecule was modified with an acridine residue. The substances synthesized were significantly more potent in inhibiting thymidine incorporation in the acid-insoluble fraction, compared to the nonmodified nucleotide. Examination of the cell cycle progression of Molt-4 cells has demonstrated a considerable shift of cells from G₂/M stage to G₁, the process being more effective in the case of modified oligonucleotides.