[Highly efficient site-directed RNA cleavage by imidazole-containing conjugates of antisense oligonucleotides].
A method has been suggested for the synthesis of conjugates of oligodeoxyribonucleotides with chemical constructs mimicking ribonuclease A active center for directed fragmentation of RNA. The method is based on the sequential addition of linker group, 9-(methylamino)anthracene, to 5' or 3' terminal phosphate of oligonucleotide and then imidazole-containing construct by cycloaddition reaction. The conjugates of oligonucleotides complementary to regions 44-61 (2B-R) and 60-76 (1C-R) of yeast phenylalanine tRNA demonstrated ability to cleave tRNA(Phe) under physiological conditions preferably at the sole phosphodiester bond (C63-A64 for 2B-R and C56-G57 for 1C-R, respectively). The half-time of tRNA(Phe) hydrolysis in the presence of 2B-R conjugate was 30 min at 2B-R concentration of 10 microM and several minutes at conjugate concentration of 50 microM.
Beloglazova
N G
NG
Institute of Bioorganic Chemistry, Siberian Division, Russian Academy of Sciences, Novosibirsk, 630090 Russia.
Epanchintsev
A Iu
AIu
Sil'nikov
V N
VN
Zenkova
M A
MA
Vlasov
V V
VV
D001483:Base Sequence; D001671:Biochemistry / Q000379:methods*; D006868:Hydrolysis; D007093:Imidazoles / Q000737:chemistry*; D007700:Kinetics; D008969:Molecular Sequence Data; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D012360:RNA, Transfer, Phe / Q000737:chemistry; D012259:Ribonuclease, Pancreatic / Q000737:chemistry
D007093:Imidazoles; D016376:Oligonucleotides, Antisense; D012360:RNA, Transfer, Phe; D012313:RNA; C029899:imidazole; D012259:Ribonuclease, Pancreatic