TY - JOUR
T1 - Spectroscopic, thermodynamic and kinetic analysis of selective triplex formation by peptide nucleic acid with double-stranded RNA over its DNA counterpart
AU - Sato, Takaya
AU - Sato, Yusuke
AU - Nishizawa, Seiichi
N1 - Funding Information:
Japan Society for the Promotion of Science (JSPS); Grant‐in‐Aid for Scientific Research (B), Grant/Award Numbers: 20H02761, 16H04159 Funding information
Funding Information:
We thank Prof. M. Ueda of the Tohoku University Graduate School of Science for use of the ITC equipment. This work was supported by Grant‐in‐Aid for Scientific Research (B) (16H04159 and 20H02761) from Japan Society for the Promotion of Science (JSPS).
Publisher Copyright:
© 2021 Wiley Periodicals LLC.
PY - 2022/1
Y1 - 2022/1
N2 - Unlike conventional triplex-forming oligonucleotide (TFO), triplex-forming peptide nucleic acid (PNA) can tightly bind with double-stranded RNA (dsRNA) than double-stranded DNA (dsDNA). Here, we performed spectroscopic, thermodynamic and kinetic experiments for triplex formation by PNA to examine different binding behaviors between PNA − dsRNA and PNA − dsDNA triplexes. We found 9-mer PNA (cytosine content of 66%) formed the thermally stable triplex with dsRNA compared to dsDNA over a wide range of pH (5.5-8.0), salt concentration (50-500 mM NaCl). Both the calorimetric binding constant and the association rate constant for dsRNA were larger than those for dsDNA, indicating the favorable association process for the PNA − dsRNA triplex formation. Comparison with the DNA/RNA heteroduplexes revealed that the DNA strand was detrimental to the triplex stability for PNA, a contrasting result for conventional TFO. The keys underlying the difference in the triplex formation of PNA with different duplexes appear to be the conformational adoptability and the geometric compatibility of PNA to fit the deep, narrow major groove of dsRNA and the helical rigidity difference of the duplexes. Our results emphasize the importance of both the sugar puckering of the duplex and the appropriate conformational flexibility of PNA for the triplex formation.
AB - Unlike conventional triplex-forming oligonucleotide (TFO), triplex-forming peptide nucleic acid (PNA) can tightly bind with double-stranded RNA (dsRNA) than double-stranded DNA (dsDNA). Here, we performed spectroscopic, thermodynamic and kinetic experiments for triplex formation by PNA to examine different binding behaviors between PNA − dsRNA and PNA − dsDNA triplexes. We found 9-mer PNA (cytosine content of 66%) formed the thermally stable triplex with dsRNA compared to dsDNA over a wide range of pH (5.5-8.0), salt concentration (50-500 mM NaCl). Both the calorimetric binding constant and the association rate constant for dsRNA were larger than those for dsDNA, indicating the favorable association process for the PNA − dsRNA triplex formation. Comparison with the DNA/RNA heteroduplexes revealed that the DNA strand was detrimental to the triplex stability for PNA, a contrasting result for conventional TFO. The keys underlying the difference in the triplex formation of PNA with different duplexes appear to be the conformational adoptability and the geometric compatibility of PNA to fit the deep, narrow major groove of dsRNA and the helical rigidity difference of the duplexes. Our results emphasize the importance of both the sugar puckering of the duplex and the appropriate conformational flexibility of PNA for the triplex formation.
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U2 - 10.1002/bip.23474
DO - 10.1002/bip.23474
M3 - Article
C2 - 34478151
AN - SCOPUS:85114132933
VL - 113
JO - Biopolymers
JF - Biopolymers
SN - 0006-3525
IS - 1
M1 - e23474
ER -