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

Y. S. Cho-Chung, M. V. Nesterova, E. S. Severin, S. V. Vinogradov

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)767-773
Number of pages7
JournalBiochemistry international
Volume25
Issue number4
Publication statusPublished - Dec 1 1991

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ASJC Scopus subject areas

  • Biochemistry

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