Synthesis and ribonuclease activity of oligonucleotides with N3-terpyridine x Cu(II)-linked thymine residues.
In previous studies of RNA cleavage, we prepared 2'-O-methyloligonucleotide-terpyridine x Cu(II) complex(es) as sequence-specific artificial ribonucleases, in which the terpyridine group was attached to the nucleoside-sugar moiety. We found that the antisense 2'-O-methyloligomer with two terpyridine x Cu(II) complexes at contiguous internal sites was most active, and precisely cleaved the target RNA oligomer at the predetermined site. In order to explore more efficient cleavers, we have constructed a structurally similar 18-mer, but with two modified thymidine residues, in which the complex was attached to the base-N(3) position by a hydroxyethyl linker. The reaction of the target RNA 24-mer with a 10-fold excess of the new agent, in the presence of Cu(II) ions, and at pH 7.5 and 37 degrees C, revealed that the substrate was almost completely cleaved after 10 hr, and that the cleavage occurred at two contiguous sites. The activity of the new cleaver was more than half of that of the previous cleaver.
Hara
Kazuhiro
K
Department of Applied and Bioapplied Chemistry, Graduate School of Engineering, Osaka City University, Sugimoto 3-3-138, Sumiyoshi-ku, Osaka 558-8585, Japan.
Kitamura
Masaya
M
Inoue
Hideo
H
D009841:Oligonucleotides / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D012313:RNA / Q000737:chemistry / Q000378:metabolism; D012260:Ribonucleases / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism
D009841:Oligonucleotides; D009942:Organometallic Compounds; D011725:Pyridines; D012313:RNA; D012260:Ribonucleases