~(19)F NMR Spectroscopic Analysis of the Binding Modes in Triple- Helical Peptide Nucleic Acid (PNA)/MicroRNA Complexes

摘要

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-ylacetyl 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.