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 GI, the process being more effective in the case of modified oligonucleotides.
Cho-Chung
Y S
YS
Laboratory of Tumor Immunology and Biology, National Cancer Institute, NIH, Bethesda, Maryland 20892.
Nesterova
M V
MV
Severin
E S
ES
Vinogradov
S V
SV
D001483:Base Sequence; D002352:Carrier Proteins / Q000235:genetics*; D002455:Cell Division / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics / Q000494:pharmacology*; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000235:genetics; D016372:RNA, Antisense / Q000235:genetics; D012334:RNA, Neoplasm / Q000235:genetics; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D009838:Oligodeoxyribonucleotides; D047428:Protein Kinase Inhibitors; D016372:RNA, Antisense; D012334:RNA, Neoplasm; C015482:protein kinase modulator; D000242:Cyclic AMP; D011494:Protein Kinases