Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides
Abstract Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been employed for the photodynamic regulation of gene expression by the photo-cross-linking of psoralen with the target DNA. However, stable triplex formation requires a consecutive purine base sequence in one strand of the...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2025-01-01
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| Series: | Communications Chemistry |
| Online Access: | https://doi.org/10.1038/s42004-025-01416-2 |
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| author | Yu Mikame Haruki Toyama Chikara Dohno Takehiko Wada Asako Yamayoshi |
| author_facet | Yu Mikame Haruki Toyama Chikara Dohno Takehiko Wada Asako Yamayoshi |
| author_sort | Yu Mikame |
| collection | DOAJ |
| description | Abstract Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been employed for the photodynamic regulation of gene expression by the photo-cross-linking of psoralen with the target DNA. However, stable triplex formation requires a consecutive purine base sequence in one strand of the target DNA duplexes. The pyrimidine-base interruption in the consecutive purine base sequence drastically decreases the thermodynamic stability of the corresponding triplex, which hampers the TFO application. Here, we propose a design of the Ps-TFO for stable triplex formation with target DNA sequences containing pyrimidine-base interruptions under physiological conditions. This Ps-TFO, named 1’(one)-psoralen-conjugated triplex-forming oligonucleotide (OPTO), incorporates a synthesized nucleoside mimic 1’-psoralen-conjugated deoxyribose to increase the thermodynamic stability of the corresponding triplex by the intercalation of psoralen. The triplex-forming abilities of the OPTO were successfully demonstrated in combination with LNA and 5-methylcytosine, indicating that the use of OPTO will expand the range of the target sequences of TFO for photodynamic gene regulation. |
| format | Article |
| id | doaj-art-885adc6aad9b4d0cb84eda25a9603ae5 |
| institution | Kabale University |
| issn | 2399-3669 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Chemistry |
| spelling | doaj-art-885adc6aad9b4d0cb84eda25a9603ae52025-01-26T12:19:08ZengNature PortfolioCommunications Chemistry2399-36692025-01-018111010.1038/s42004-025-01416-2Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotidesYu Mikame0Haruki Toyama1Chikara Dohno2Takehiko Wada3Asako Yamayoshi4Chemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki UniversityChemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki UniversitySANKEN (The Institute of Scientific and Industrial Research), Osaka UniversityIMRAM (Institute of Multidisciplinary Research for Advanced Materials), Tohoku UniversityChemistry of Functional Molecules, Graduate School of Biomedical Sciences, Nagasaki UniversityAbstract Psoralen-conjugated triplex-forming oligonucleotides (Ps-TFOs) have been employed for the photodynamic regulation of gene expression by the photo-cross-linking of psoralen with the target DNA. However, stable triplex formation requires a consecutive purine base sequence in one strand of the target DNA duplexes. The pyrimidine-base interruption in the consecutive purine base sequence drastically decreases the thermodynamic stability of the corresponding triplex, which hampers the TFO application. Here, we propose a design of the Ps-TFO for stable triplex formation with target DNA sequences containing pyrimidine-base interruptions under physiological conditions. This Ps-TFO, named 1’(one)-psoralen-conjugated triplex-forming oligonucleotide (OPTO), incorporates a synthesized nucleoside mimic 1’-psoralen-conjugated deoxyribose to increase the thermodynamic stability of the corresponding triplex by the intercalation of psoralen. The triplex-forming abilities of the OPTO were successfully demonstrated in combination with LNA and 5-methylcytosine, indicating that the use of OPTO will expand the range of the target sequences of TFO for photodynamic gene regulation.https://doi.org/10.1038/s42004-025-01416-2 |
| spellingShingle | Yu Mikame Haruki Toyama Chikara Dohno Takehiko Wada Asako Yamayoshi Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides Communications Chemistry |
| title | Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides |
| title_full | Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides |
| title_fullStr | Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides |
| title_full_unstemmed | Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides |
| title_short | Development and functional evaluation of a psoralen-conjugated nucleoside mimic for triplex-forming oligonucleotides |
| title_sort | development and functional evaluation of a psoralen conjugated nucleoside mimic for triplex forming oligonucleotides |
| url | https://doi.org/10.1038/s42004-025-01416-2 |
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