title: Preferred RNA binding sites for a threading intercalator revealed by in vitro evolution.
abstract: In pursuit of small molecules capable of controlling the function of RNA targets, we have explored the RNA binding properties of peptide-acridine conjugates (PACs). In vitro evolution (SELEX) was used to isolate RNAs capable of binding the PAC Ser-Val-Acr-Arg, where Acr is an acridine amino acid. The PAC binds RNA aptamers selectively and with a high degree of discrimination over DNA. PAC binding sites contain the base-paired 5'-CpG-3' sequence, a known acridine intercalation site. However, RNA structure flanking this sequence causes binding affinities to vary over 30-fold. The preferred site (K(D) = 20 nM) contains a base-paired 5'-CpG-3' step flanked on the 5' side by a 4 nt internal loop and the 3' side by a bulged U. Several viral 5'- and 3'-UTR RNA sequences that likely form binding sites for this PAC are identified.
authors.affiliation: Department of Chemistry, University of Utah, Salt Lake City, UT 84112, USA.
authors.forename: Coby B
authors.initials: CB
authors.lastname: Carlson
authors.forename: Momchilo
authors.initials: M
authors.lastname: Vuyisich
authors.forename: Barry D
authors.initials: BD
authors.lastname: Gooch
authors.forename: Peter A
authors.initials: PA
authors.lastname: Beal
mesh_terms: D000166:Acridines / Q000737:chemistry; D001665:Binding Sites; D002614:Chelating Agents; D003001:Cloning, Molecular; D018983:DNA Footprinting; D019020:Directed Molecular Evolution / Q000379:methods*; D004492:Edetic Acid; D007202:Indicators and Reagents; D007364:Intercalating Agents / Q000494:pharmacology*; D007501:Iron / Q000737:chemistry; D009690:Nucleic Acid Conformation; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry; D012313:RNA / Q000096:biosynthesis / Q000737:chemistry / Q000378:metabolism*; D012260:Ribonucleases / Q000737:chemistry; D020349:Surface Plasmon Resonance
chemical_list: D000166:Acridines; D002614:Chelating Agents; D007202:Indicators and Reagents; D007364:Intercalating Agents; D019151:Peptide Library; D010455:Peptides; D012313:RNA; D004492:Edetic Acid; D007501:Iron; D012260:Ribonucleases