[The effect of modifying terminal oligonucleotide linkages on their stability in cell cultures]

The effect of modification of terminal groups of deoxyribooligonucleotides on their stability in cell culture and inside mammalian cells, namely Krebs 2, ascite carcinoma (KAC) and mouse fibroblasts L929, has been investigated. Oligonucleotides and their derivatives were found to be stable in culture medium without serum during 24 h. In the medium with KAC cells or ascitic fluid, orthophosphate was rapidly eliminated from the 5'-terminus of the oligonucleotides. In KAC cells, the scission of 5'-phosphomonoester bonds was accompanied by reutilization of the phosphate and by degradation of oligonucleotides to mononucleotides. In the medium with fibroblasts L929, the oligonucleotides were degraded from the 3'-end to tetranucleotides. Modification of oligonucleotides at the 5'-terminus by amidation made the 5'-phosphate groups resistant to KAC. Modification of the oligonucleotides by coupling of cholesterol or phenazinium to the 3'-terminus sufficiently increases their stability in the medium with fibroblasts L929, in that with Krebs 2 ascite carcinoma cells and inside the cells.