ORGN 308 |
| Duplex RNA is involved in numerous biological phenomena including RNA interference, the interferon antiviral response, the trafficking and editing of cellular RNA, and the generation of microRNA regulators of translation. Many proteins involved in these processes have double stranded RNA-binding motifs (dsRBMs) that give them the ability to bind duplex RNA preferentially over single stranded RNA or DNA. Here we describe RNA recognition properties for proteins that have dsRBMs including PKR, an RNA-dependent protein kinase and ADAR2, an RNA-editing adenosine deaminase. We have also investigated the use of helix-threading peptides as a general recognition motif for duplex RNA. Here peptide-intercalator conjugates with an acridine or quinoline chromophore introduced into the peptide backbone are discussed. These compounds bind duplex RNA by threading intercalation with peptide appendages on the chromophore localized in the different helix grooves. In vitro evolution (SELEX) of RNA binding sites and structure-activity relationship studies have revealed preferred RNA motifs that bind selectively to helix-threading peptides. Data will be presented regarding their binding affinity and selectivity for various duplex RNA targets. |
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Frontiers in Bio-organic Chemistry and Chemical Biology
1:00 PM-5:00 PM, Monday, 14 March 2005 Convention Center -- Ballroom 20 C-D, Oral
Division of Organic Chemistry |