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Optimization of the Alkyl Linker of TO Base Surrogate in Triplex‐Forming PNA for Enhanced Binding to Double‐Stranded RNA
Author(s) -
Sato Takaya,
Sato Yusuke,
Nishizawa Seiichi
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.201604676
Subject(s) - linker , alkyl , rna , chemistry , base (topology) , combinatorial chemistry , stereochemistry , polymer chemistry , biochemistry , organic chemistry , computer science , mathematics , gene , mathematical analysis , operating system
A series of triplex‐forming peptide nucleic acid (TFP) probes carrying a thiazole orange (TO) base surrogate through an alkyl linker was synthesized, and the interactions between these so‐called tFIT probes and purine‐rich sequences within double‐stranded RNA (dsRNA) were examined. We found that the TO base surrogate linker significantly affected both the binding affinity and the fluorescence response upon triplex formation with the target dsRNA. Among the probes examined, the TO base surrogate connected through the propyl linker in the tFIT probes increased the binding affinity by a factor of ten while maintaining its function as the fluorescent universal base. Isothermal titration calorimetry experiments revealed that the increased binding affinity resulted from the gain in the binding enthalpy, which could be explained by the enhanced π‐stacking interaction between the TO base surrogate and the dsRNA part of the triplex. We expect that these results will provide a molecular basis for designing strong binding tFIT probes for fluorescence sensing of various kinds of purine‐rich dsRNAs sequences including those carrying a pyrimidine‐purine inversion. The obtained data also offers a new insight into further development of the universal bases incorporated in TFP.