scholarly journals SNP Discrimination by Tolane-Modified Peptide Nucleic Acids: Application for the Detection of Drug Resistance in Pathogens

Molecules ◽  
2020 ◽  
Vol 25 (4) ◽  
pp. 769 ◽  
Author(s):  
Kenji Takagi ◽  
Tenko Hayashi ◽  
Shinjiro Sawada ◽  
Miku Okazaki ◽  
Sakiko Hori ◽  
...  

During the treatment of viral or bacterial infections, it is important to evaluate any resistance to the therapeutic agents used. An amino acid substitution arising from a single base mutation in a particular gene often causes drug resistance in pathogens. Therefore, molecular tools that discriminate a single base mismatch in the target sequence are required for achieving therapeutic success. Here, we synthesized peptide nucleic acids (PNAs) derivatized with tolane via an amide linkage at the N-terminus and succeeded in improving the sequence specificity, even with a mismatched base pair located near the terminal region of the duplex. We assessed the sequence specificities of the tolane-PNAs for single-strand DNA and RNA by UV-melting temperature analysis, thermodynamic analysis, an in silico conformational search, and a gel mobility shift assay. As a result, all of the PNA-tolane derivatives stabilized duplex formation to the matched target sequence without inducing mismatch target binding. Among the different PNA-tolane derivatives, PNA that was modified with a naphthyl-type tolane could efficiently discriminate a mismatched base pair and be utilized for the detection of resistance to neuraminidase inhibitors of the influenza A/H1N1 virus. Therefore, our molecular tool can be used to discriminate single nucleotide polymorphisms that are related to drug resistance in pathogens.

2004 ◽  
Vol 68 (2) ◽  
pp. 360-368 ◽  
Author(s):  
Toshiyuki TAKIYA ◽  
Satoshi FUTO ◽  
Mika TSUNA ◽  
Takanori NAMIMATSU ◽  
Tetsuya SAKANO ◽  
...  

Biochemistry ◽  
2001 ◽  
Vol 40 (1) ◽  
pp. 53-64 ◽  
Author(s):  
Donald F. Doyle ◽  
Dwaine A. Braasch ◽  
Bethany A. Janowski ◽  
David R. Corey

2021 ◽  
Vol 23 (1) ◽  
pp. 219-228
Author(s):  
Nabanita Saikia ◽  
Mohamed Taha ◽  
Ravindra Pandey

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.


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