Structure-activity relationship of an antisense oligonucleotide-two Cu(II) complex conjugate as an artificial ribonuclease.
We previously demonstrated that an antisense 2'-O-methyloligonucleotide, with two terpyridine*Cu(II) complexes at contiguous internal sites, was highly active as a sequence-specific artificial ribonuclease. Two kinds of terpyridine-linked uridine derivatives (Ut and tU(L)) were used for its construction, and the residue on the 5'-side (Ut) was the derivative with terpyridine attached to the 2'-oxygen via a short linker arm. To examine the structure-activity relationship of this type of RNA cleaver, we synthesized an analogous RNA cleaver with the inosine counterpart (It) on the 5'-side, since inosine can base-pair with A, U or C. Using the RNA cleavers and the RNA oligomer substrates, we examined the effect of base-pair formation at the Ut (or It) and tU(L) sites on the activities of the cleavers. The cleavage reactions revealed that, for this type of RNA cleaver, a base-pair at the 5'-side and no base-pair at the 3'-side were required for high activity. In addition, for the 5'-side-It residue, a normal base-pair (I-C pair) was needed.
Mukoguchi
Daiki
D
Department of Applied and Bioapplied Chemistry, Graduate School of Engineering, Osaka City University, Sumiyoshi-ku, Osaka 558-8585, Japan.
Sakamoto
Satoshi
S
Takayama
Hiroshi
H
Kitamura
Masaya
M
Inoue
Hideo
H
D020029:Base Pairing; D016376:Oligonucleotides, Antisense / Q000138:chemical synthesis / Q000737:chemistry*; D009942:Organometallic Compounds / Q000737:chemistry*; D012313:RNA / Q000737:chemistry; D012260:Ribonucleases / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014529:Uridine / Q000031:analogs & derivatives* / Q000737:chemistry
D016376:Oligonucleotides, Antisense; D009942:Organometallic Compounds; D012313:RNA; D012260:Ribonucleases; D014529:Uridine