Properties of novel antisense oligonucleotides containing 2'-O-modified adenosine with a photo-reactive group.
In order to enhance the efficiency of antisense molecules for target RNA regulation, a novel photo-reactive antisense oligonucleotide was developed. We designed and synthesized a photo-reactive antisense oligonucleotide containing an adenosine in which 2'-OH was modified with 4,5',8-trimethylpsoralen (Ps) via an ethoxymethylene linkage (2'-Ps-eom). We evaluated the photo-cross-linking efficiency and sequence specificity toward complementary RNA (match-RNA). 2'-Ps-eom was selectively photo-cross-linked to the match-RNA. The photo-cross-linking efficiency was about 75% upon UVA-irradiation (365 nm) for 10 min. Previously, we reported oligonucleotides that had an adenosine anchoring Ps at 2'-O-position via a methylene linkage (2'-Ps-met). The photo-cross-linking efficiency of 2'-Ps-met and match-RNA was about 35% upon UVA-irradiation for 120 min. The photo-cross-linking efficiency of 2'-Ps-eom was dramatically enhanced in comparison with the one of 2'-Ps-met.
Higuchi
Maiko
M
Department of Biomolecular Engineering, Kyoto Institute of Technology, Matsugasaki, Sakyo-ku, Kyoto 606-8585, Japan.
Sakamoto
Takashi
T
Kobori
Akio
A
Murakami
Akira
A
D000241:Adenosine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects; D011564:Furocoumarins / Q000138:chemical synthesis / Q000737:chemistry* / Q000528:radiation effects; D008958:Models, Molecular; D016376:Oligonucleotides, Antisense / Q000737:chemistry* / Q000528:radiation effects; D010777:Photochemistry; D014466:Ultraviolet Rays
C522099:2'-(4,5',8-trimethylpsoralen-4-yl)adenosine; D011564:Furocoumarins; D016376:Oligonucleotides, Antisense; D000241:Adenosine