Novel psoralen-conjugated antisense oligonucleotides having high photocross-linking efficiency

CARB 58

Maiko Higuchi, Asako Yamayoshi, Akio Kobori, and Akira Murakami, akiram@kit.ac.jp. Department of Biomolecular Engineering, Kyoto Institute of Technology, gosyokaido-cho, Matsugasaki, Sakyo, Kyoto, 606-8585, Japan
In order to enhance the efficiency of antisense molecules for target RNA regulation, novel photo-reactive antisense oligonucleotides were developed. Previously, we reported photo-reactive oligonucleotides containing an adenosine whose 2'-OH was modified with 4,5',8-trimethylpsoralen (psoralen) via a methylene linker (2'-Ps-met) cross-linked with the complementary RNA (match-RNA) and scarcely did with the RNA having a single mismatch base(mismatch-RNA). In order to examine the relationship between tether identity and photo-cross-linking efficiency, we designed photo-reactive oligonucleotides containing 2'-O-psoralen-conjugated adenosine derivatives with various linkers such as an amidomethylene linker (2'-Ps-amd), an ethoxymethylene one (2'-Ps-eom), a propoxymethylene one (2'-Ps-eom) and a butoxymethylene one (2'-Ps-bom). We evaluated the photo-cross-linking efficiency of the photo-reactive oligonucleotides with match-RNA. The efficiency of photo-cross-linking and the sequence selectivity largely depended on the structure and the length of the linker.
 

General Posters
6:00 PM-8:00 PM, Tuesday, August 21, 2007 BCEC -- Exhibit Hall - B2, Poster

Division of Carbohydrate Chemistry

The 234th ACS National Meeting, Boston, MA, August 19-23, 2007