title: 19F NMR Spectroscopic Analysis of the Binding Modes in Triple-Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes.
abstract: Triplex-forming peptide nucleic acids (TFPNAs) were targeted to double-helical regions of19F-labeled RNA hairpin models (a UA-rich duplex with a hexaethylene glycol (heg) loop and a microRNA model, miR-215). In addition to conventional UV- and circular dichroism (CD)-based detection, binding was monitored by19F NMR spectroscopy. Detailed information on the stoichiometry and transition between the triple-helical peptide nucleic acid (PNA)/RNA and (PNA)2/RNA binding modes could be obtained. γ-(R)-Hydroxymethyl-modified thymine-1-yl- and 2-aminopyridin-3-yl-acetyl derivatives of TFPNAs were additionally synthesized, which were targeted to the same RNA models, and the effect of the γ-(R)-hydroxymethyl group on binding was studied. An appropriate pattern of γ-(R)-hydroxymethyl modifications reduced the stability of the ternary complex and preferred stoichiometric binding to the miR-215 model.
authors.affiliation: Department of Chemistry, University of Turku, Turku, 20014, Finland.
authors.forename: Ville
authors.initials: V
authors.lastname: Tähtinen
authors.affiliation: Department of Chemistry, University of Turku, Turku, 20014, Finland.
authors.forename: Lotta
authors.initials: L
authors.lastname: Granqvist
authors.affiliation: Department of Chemistry, University of Turku, Turku, 20014, Finland.|Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83, Huddinge, Stockholm, Sweden.
authors.forename: Merita
authors.initials: M
authors.lastname: Murtola
authors.affiliation: Department of Biosciences and Nutrition, Karolinska Institutet, Novum, 141 83, Huddinge, Stockholm, Sweden.
authors.forename: Roger
authors.initials: R
authors.lastname: Strömberg
authors.affiliation: Department of Chemistry, University of Turku, Turku, 20014, Finland.
authors.forename: Pasi
authors.initials: P
authors.lastname: Virta
mesh_terms: D001483:Base Sequence; D002942:Circular Dichroism; D005461:Fluorine / Q000737:chemistry; D035683:MicroRNAs / Q000737:chemistry* / Q000378:metabolism; D019906:Nuclear Magnetic Resonance, Biomolecular; D009690:Nucleic Acid Conformation; D020135:Peptide Nucleic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet
chemical_list: D035683:MicroRNAs; D020135:Peptide Nucleic Acids; D005461:Fluorine
keywords: NMR spectroscopy; RNA; fluorine; helical structures; nucleic acids