WEKO3
アイテム
Photo-cross-linking oligonucleotides for bioorthogonal regulation of gene expression
http://hdl.handle.net/10212/2382
http://hdl.handle.net/10212/23820c195a2b-8a47-440b-875a-7abc5a3c9a4e
| 名前 / ファイル | ライセンス | アクション |
|---|---|---|
内容の要約 (255.2 KB)
|
|
|
|
内容・審査結果の要旨 (162.4 KB)
|
|
| Item type | 学位論文 / Thesis or Dissertation(1) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| 公開日 | 2019-01-15 | |||||||||
| タイトル | ||||||||||
| タイトル | Photo-cross-linking oligonucleotides for bioorthogonal regulation of gene expression | |||||||||
| 言語 | en | |||||||||
| その他のタイトル | ||||||||||
| その他のタイトル | 光架橋性核酸を利用した遺伝子発現制御 | |||||||||
| 言語 | ja | |||||||||
| 作成者 |
杉原, 悠太
× 杉原, 悠太
|
|||||||||
| アクセス権 | ||||||||||
| アクセス権 | open access | |||||||||
| アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | nucleic acids | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | photo-cross-linking | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | α-haloaldehyde | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | diazirine | |||||||||
| 主題 | ||||||||||
| 言語 | en | |||||||||
| 主題Scheme | Other | |||||||||
| 主題 | point mutation | |||||||||
| 内容記述 | ||||||||||
| 内容記述タイプ | Abstract | |||||||||
| 内容記述 | Regulation of gene expression in sequence-specific manner in biological systems without damaging the biological activities are much important issues in medical, biological and molecular biological fields. Photo-cross-linking oligonucleotides bearing photo-induced reactive moieties are powerful tools because the photo-induced cross-linking reaction can be spatiotemporally and bioorthogonally controlled via ultraviolet (UV) irradiation. In this thesis, I develop novel photo-cross-linking oligonucleotides and investigate their properties in vitro and in cells. Chapter 1 concerns the development of novel photo-cross-linking oligonucleotides (PBA-ODNs) bearing a photoresponsive α-bromoaldehyde as a photoreactive group to investigate the kinetics of the photo-cross-linking reactions with target molecules. The photo-cross-linking oligonucleotides reacted with target nucleotides having an adenine or a cytosine at the frontal position of the reactive aldehyde with much higher kinetic rates than photoresponsive α-chloroaldehyde-conjugated oligonucleotides reacted. Chapter 2 concerns the inhibition effects of photo-cross-linking oligonucleotides (PXA-ORNs) bearing a photoresponsive α-haloaldehyde on mRNA translation. Using HeLa cells expressing GFP, PXA-ORNs effectively suppressed the fluorescent intensity of GFP under UV-irradiation conditions. These results suggest that PXA-ORNs could be activated in cells and inhibit the mRNA translation in sequence-specific manner. Chapter 3 concerns the development of novel photo-cross-lining oligonucleotides (proPCA-ODNs) bearing a caged α-chloroaldehyde group conjugated to a 2-methylpropanediyl backbone (proPCA) in the middle of the strand for selective reactions with RNAs having point mutations. Photo-cross-linking studies of proPCA-ODNs with complementary oligoribonucleotides (ORNs) revealed that proPCA-ODNs reacts efficiently and selectively with the target ORNs that have an adenosine or cytidine residue at a frontal position of the proPCA residue without adverse effects of bases adjacent to the mutation site. Chapter 4 concerns the development of novel photo-cross-linking oligonucleotides (X-ODNs) bearing an adenosine derivative with a 3-trifluoromethylphenyldiazirine at 2’-position for rapid interstrand cross-linking formations. Photo-cross-linking studies revealed that the X-ODNs selectively cross-linked with the oligo-DNAs (and not with the oligo-RNAs), and 5 min of UV irradiation was sufficient for the photo-crosslinking reactions. | |||||||||
| 言語 | en | |||||||||
| 日付 | ||||||||||
| 日付 | 2017-03-24 | |||||||||
| 日付タイプ | Issued | |||||||||
| 言語 | ||||||||||
| 言語 | eng | |||||||||
| 資源タイプ | ||||||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_db06 | |||||||||
| 資源タイプ | doctoral thesis | |||||||||
| 学位授与番号 | ||||||||||
| 学位授与番号 | 甲第825号 | |||||||||
| 学位名 | ||||||||||
| 言語 | ja | |||||||||
| 学位名 | 博士（工学） | |||||||||
| 学位授与年月日 | ||||||||||
| 学位授与年月日 | 2017-03-24 | |||||||||
| 学位授与機関 | ||||||||||
| 学位授与機関識別子Scheme | kakenhi | |||||||||
| 学位授与機関識別子 | 14303 | |||||||||
| 言語 | ja | |||||||||
| 学位授与機関名 | 京都工芸繊維大学 | |||||||||
