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19 F NMR Spectroscopic Analysis of the Binding Modes in Triple‐Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes
Author(s) -
Tähtinen Ville,
Granqvist Lotta,
Murtola Merita,
Strömberg Roger,
Virta Pasi
Publication year - 2017
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201700601
Subject(s) - peptide nucleic acid , nucleic acid , circular dichroism , chemistry , rna , duplex (building) , peptide , stereochemistry , nuclear magnetic resonance spectroscopy , triple helix , thymine , oligonucleotide , hydroxymethyl , dna , nucleic acid thermodynamics , nucleic acid structure , biochemistry , gene
Triplex‐forming peptide nucleic acids (TFPNAs) were targeted to double‐helical regions of 19 F‐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 19 F 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.