ORGN 514 |
| Zhaohui Yan and Anne M. Baranger. Department of Chemistry, Wesleyan University, Middletown, CT 06459 |
| Small molecules that bind RNA tightly and specifically would be important tools for understanding and controlling biological processes involving RNA. We are investigating small molecule recognition of tetraloop RNAs, which are exceptionally stable, four-nucleotide RNA stem loops. Fluorescence experiments showed that an aminoacridine derivative (AD1), tetraaminoquinozaline, quinacrine and neomycin B bound a GAAA tetraloop, but kanamycin did not. AD1 bound tetraloop RNA more tightly than the other compounds tested. A micromolar dissociation constant of the AD1-GAAA tetraloop complex was obtained by fluorescence measurements using RNA labeled with 2-aminopurine. Enzymatic and chemical cleavage of GAAA and GCAA tetraloops showed that these RNAs have compact and stable structures, which agrees with previous structural studies. Lead acetate and RNase I footprinting experiments suggested that AD1 binds to the junction region between the stem and loop of the GAAA tetraloop. In addition, the virtual screening of small molecule databases for small molecules that bind to tetraloop RNA will be discussed. |
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Bioorganic, Molecular Recognition, Asymmetric Reactions and Syntheses
11:00 AM-1:00 PM, Wednesday, September 10, 2003 Javits Convention Center -- Hall 1B/1C, Poster
Sci-Mix
Division of Organic Chemistry |