Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties
Synthetic unnatural base pairs have been proven to be attractive tools for the development of DNA-based biotechnology. Our group has very recently reported on alkynylated purine–pyridazine pairs, which exhibit selective and stable base-pairing via hydrogen bond formation between pseudo-nucleobases i...
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| Format: | Article |
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MDPI AG
2023-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/28/4/1766 |
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| author | Hidenori Okamura Giang Hoang Trinh Zhuoxin Dong Wenjue Fan Fumi Nagatsugi |
| author_facet | Hidenori Okamura Giang Hoang Trinh Zhuoxin Dong Wenjue Fan Fumi Nagatsugi |
| author_sort | Hidenori Okamura |
| collection | DOAJ |
| description | Synthetic unnatural base pairs have been proven to be attractive tools for the development of DNA-based biotechnology. Our group has very recently reported on alkynylated purine–pyridazine pairs, which exhibit selective and stable base-pairing via hydrogen bond formation between pseudo-nucleobases in the major groove of duplex DNA. In this study, we attempted to develop an on-column synthesis methodology of oligodeoxynucleotides (ODNs) containing alkynylated purine derivatives to systematically explore the relationship between the structure and the corresponding base-pairing ability. Through Sonogashira coupling of the ethynyl pseudo-nucleobases and CPG-bound ODNs containing 6-iodopurine, we have demonstrated the synthesis of the ODNs containing three <sup>N</sup>Pu derivatives (<sup>N</sup>Pu1, <sup>N</sup>Pu2, <sup>N</sup>Pu3) as well as three <sup>O</sup>Pu derivatives (<sup>O</sup>Pu1, <sup>O</sup>Pu2, <sup>O</sup>Pu3). The base-pairing properties of each alkynylated purine derivative revealed that the structures of pseudo-nucleobases influence the base pair stability and selectivity. Notably, we found that <sup>O</sup>Pu1 bearing 2-pyrimidinone exhibits higher stability to the complementary <sup>N</sup>Pz than the original <sup>O</sup>Pu, thereby demonstrating the potential of the on-column strategy for convenient screening of the alkynylated purine derivatives with superior pairing ability. |
| first_indexed | 2024-03-11T08:21:30Z |
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| id | doaj.art-e8138495f98d4e649aa9a5fb46e38520 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-11T08:21:30Z |
| publishDate | 2023-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-e8138495f98d4e649aa9a5fb46e385202023-11-16T22:23:01ZengMDPI AGMolecules1420-30492023-02-01284176610.3390/molecules28041766Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing PropertiesHidenori Okamura0Giang Hoang Trinh1Zhuoxin Dong2Wenjue Fan3Fumi Nagatsugi4Institute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Miyagi, JapanInstitute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Miyagi, JapanInstitute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Miyagi, JapanInstitute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Miyagi, JapanInstitute of Multidisciplinary Research for Advanced Materials, Tohoku University, 2-1-1 Katahira, Aoba-ku, Sendai 980-8577, Miyagi, JapanSynthetic unnatural base pairs have been proven to be attractive tools for the development of DNA-based biotechnology. Our group has very recently reported on alkynylated purine–pyridazine pairs, which exhibit selective and stable base-pairing via hydrogen bond formation between pseudo-nucleobases in the major groove of duplex DNA. In this study, we attempted to develop an on-column synthesis methodology of oligodeoxynucleotides (ODNs) containing alkynylated purine derivatives to systematically explore the relationship between the structure and the corresponding base-pairing ability. Through Sonogashira coupling of the ethynyl pseudo-nucleobases and CPG-bound ODNs containing 6-iodopurine, we have demonstrated the synthesis of the ODNs containing three <sup>N</sup>Pu derivatives (<sup>N</sup>Pu1, <sup>N</sup>Pu2, <sup>N</sup>Pu3) as well as three <sup>O</sup>Pu derivatives (<sup>O</sup>Pu1, <sup>O</sup>Pu2, <sup>O</sup>Pu3). The base-pairing properties of each alkynylated purine derivative revealed that the structures of pseudo-nucleobases influence the base pair stability and selectivity. Notably, we found that <sup>O</sup>Pu1 bearing 2-pyrimidinone exhibits higher stability to the complementary <sup>N</sup>Pz than the original <sup>O</sup>Pu, thereby demonstrating the potential of the on-column strategy for convenient screening of the alkynylated purine derivatives with superior pairing ability.https://www.mdpi.com/1420-3049/28/4/1766unnatural base pairDNAsolid-phase synthesisSonogashira couplingmodified nucleosidesDNA major groove |
| spellingShingle | Hidenori Okamura Giang Hoang Trinh Zhuoxin Dong Wenjue Fan Fumi Nagatsugi Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties Molecules unnatural base pair DNA solid-phase synthesis Sonogashira coupling modified nucleosides DNA major groove |
| title | Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties |
| title_full | Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties |
| title_fullStr | Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties |
| title_full_unstemmed | Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties |
| title_short | Synthesis of 6-Alkynylated Purine-Containing DNA via On-Column Sonogashira Coupling and Investigation of Their Base-Pairing Properties |
| title_sort | synthesis of 6 alkynylated purine containing dna via on column sonogashira coupling and investigation of their base pairing properties |
| topic | unnatural base pair DNA solid-phase synthesis Sonogashira coupling modified nucleosides DNA major groove |
| url | https://www.mdpi.com/1420-3049/28/4/1766 |
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