A1 Refereed original research article in a scientific journal
F-19 NMR Spectroscopic Analysis of the Binding Modes in Triple-Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes
Authors: Tahtinen Ville, Granqvist Lotta, Murtola Merita, Stromberg Roger, Virta Pasi
Publisher: WILEY-V C H VERLAG GMBH
Publication year: 2017
Journal: Chemistry - A European Journal
Journal name in source: CHEMISTRY-A EUROPEAN JOURNAL
Journal acronym: CHEM-EUR J
Volume: 23
Issue: 29
First page : 7113
Last page: 7124
Number of pages: 12
ISSN: 0947-6539
eISSN: 1521-3765
DOI: https://doi.org/10.1002/chem.201700601
Abstract
Triplex-forming peptide nucleic acids (TFPNAs) were targeted to double-helical regions of F-19-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 by F-19 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. gamma-(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 gamma-(R)-hydroxymethyl group on binding was studied. An appropriate pattern of gamma-(R)-hydroxymethyl modifications reduced the stability of the ternary complex and preferred stoichiometric binding to the miR-215 model.
Triplex-forming peptide nucleic acids (TFPNAs) were targeted to double-helical regions of F-19-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 by F-19 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. gamma-(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 gamma-(R)-hydroxymethyl group on binding was studied. An appropriate pattern of gamma-(R)-hydroxymethyl modifications reduced the stability of the ternary complex and preferred stoichiometric binding to the miR-215 model.
UTU Research Portal