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- Title
SNP Discrimination by Tolane-Modified Peptide Nucleic Acids: Application for the Detection of Drug Resistance in Pathogens.
- Authors
Takagi, Kenji; Hayashi, Tenko; Sawada, Shinjiro; Okazaki, Miku; Hori, Sakiko; Ogata, Katsuya; Kato, Nobuo; Ebara, Yasuhito; Kaihatsu, Kunihiro
- Abstract
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.
- Subjects
PEPTIDE nucleic acids; DRUG resistance; NEURAMINIDASE; BASE pairs; PATHOGENIC microorganisms; INFLUENZA A virus
- Publication
Molecules, 2020, Vol 25, Issue 4, p769
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules25040769