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Open AccessArticle

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

1
Department of Organic Fine Chemicals, The Institute of Scientific and Industrial Research, Osaka University, 8-1 Mihogaoka, Ibaraki, Osaka 567-0047, Japan
2
Graduate School of Human Development and Environment, Kobe University, 3-11 Tsurukabuto, Kobe, Hyogo 657-8501, Japan
*
Authors to whom correspondence should be addressed.
Molecules 2020, 25(4), 769; https://doi.org/10.3390/molecules25040769
Received: 7 January 2020 / Revised: 5 February 2020 / Accepted: 7 February 2020 / Published: 11 February 2020
(This article belongs to the Special Issue Peptide Nucleic Acids: Applications in Biomedical Sciences)
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. View Full-Text
Keywords: peptide nucleic acid; tolane; single nucleotide polymorphism; influenza virus; drug resistance peptide nucleic acid; tolane; single nucleotide polymorphism; influenza virus; drug resistance
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Takagi, K.; Hayashi, T.; Sawada, S.; Okazaki, M.; Hori, S.; Ogata, K.; Kato, N.; Ebara, Y.; Kaihatsu, K. SNP Discrimination by Tolane-Modified Peptide Nucleic Acids: Application for the Detection of Drug Resistance in Pathogens. Molecules 2020, 25, 769.

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