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Synthesis, thermal stability and resistance to enzymatic hydrolysis of the oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2'-O-methyluridines
| Title: | Synthesis, thermal stability and resistance to enzymatic hydrolysis of the oligonucleotides containing 5-(N-aminohexyl)carbamoyl-2'-O-methyluridines |
| Authors: | Ito, Takanori Browse this author | | Ueno, Yoshihito Browse this author | | Komatsu, Yasuo Browse this author | | Matsuda, Akira Browse this author |
| Issue Date: | May-2003 |
| Publisher: | Oxford University Press |
| Journal Title: | Nucleic Acids Research |
| Volume: | 31 |
| Issue: | 10 |
| Start Page: | 2514 |
| End Page: | 2523 |
| Publisher DOI: | 10.1093/nar/gkg374 |
| Abstract: | The synthesis of oligonucleotides (ODNs) containing 5‐(N‐aminohexyl)carbamoyl‐2′‐O‐methyluridine (D) is described, and thermal stability and resistance to enzymatic hydrolysis of the ODNs are compared with ODNs containing 5‐(N‐aminohexyl)carbamoyl‐2′‐deoxyuridine (H). The ODNs containing D and the complementary RNA demonstrated a duplex thermal stabilization of 0.4–3.9°C per modification depending on the position and the number, while the ODNs containing H with the RNA showed slightly less effective thermal stabilization. Further more, the ODNs containing D were found to be more resistant to nucleolytic hydrolysis, not only by snake venom phosphodiesterase (SVPD; a 3′‐exonuclease) but also by DNase I (an endonuclease). The half‐life of the 17mer containing five molecules of D against nucleolytic hydrolysis by SVPD was 240 times greater than the unmodified 17mer ODN, which is 1.8 times greater than the ODN containing 5Hs in the same sequence. Against DNase I, the same ODN containing 5Ds was 24 times greater stable than the unmodified 17mer and 15 times more stable than the ODN containing 5Hs. We also examined whether the duplexes formed by the ODNs containing D and the complementary RNAs could be a substrate of Escherichia coli RNase H. It was revealed that a minimum of five contiguous unmodified 2′‐deoxyribonucleosides between Ds was required to constitute a substrate of E.coli RNase H. Thus, the ODN with Ds and at least five contiguous unmodified 2′‐deoxyribonucleosides between Ds was found to be a candidate for a novel antisense molecule. |
| Type: | article |
| URI: | http://hdl.handle.net/2115/46960 |
| Appears in Collections: | 薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)
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Submitter: 松田 彰
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