权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Development of Programmed Oligosaccharide Synthesis on Nucleic Acid Template

核酸模板程序化低聚糖合成研究进展

基本信息

批准号：
22659005
负责人：
青木伸
金额：
$ 1.89万
依托单位：
Tokyo University of Science
依托单位国家：
日本
项目类别：
Grant-in-Aid for Challenging Exploratory Research
财政年份：
2010
资助国家：
日本
起止时间：
2010 至 2011
项目状态：
已结题

项目摘要

The objective of this project is to develop new methodology for oligosaccharide synthesis on DNA templates. We hypothesized that glycosyl donors having nucleobases would be aligned on DNA template due to the hydrogen bonding between complementary base pairs and glycosylation would proceeds upon addition of activators of glycosyl donors, resulting in the selective synthesis of target sequence of oligosaccharides. It also provides a new concept for the direct conversion of genetic sequence of DNA to olitosaccharide sequence.For the aforementioned purpose, we decided to design and synthesize nucleothio-glycosides, which are thioglycosides linked with nucleobases by covalent bonds, because thioglycosides are stable and can be activated by specific activators, and hence, they are used as glycosyl donors in plenty examples of oligosaccharide synthesis.First, a benzenethiol part having thymidine(T) was prepared from bromobenzene in 8 steps and then reacted with galactosyl acetate to afford th … More iogalactoside linked with thymidine(T)(T-Gal). In addition, Gal having adenosine(A-Gal) and N-acetyl-glucosamine linked with A(A-GlcNAc) were prepared in a similar manner. Recently, more convenient synthetic routes of these nucleothioglucosides were established.Secondly, it was found that glycosylation of T-Gal with glucose derivatives gave the desired disaccharides such as Gal(β1→4) Glc in a fairly good yield, proving the possibility of glycosylation of nucleobase-linked thioglycosides. However, glycosylation of T-Gal with glycosyl acceptors having adenosine units and A-GlcNAc with several acceptors were not successful under these reaction conditions, possibly because Lewis acidity of promoters is neutralized by adenosine moiety of these substrates. Therefore, we have tested several reaction conditions(activators, solvent, and temperature) and finally found that a combination of Tol-SCl & AgOTf(OTf=triflate) gave the target disaccharides in moderate or high chemical yields.As for DNA template to program oligosaccharide sequences, we have synthesized A, T, G, and C derivatives having glycine backbone. Coupling reactions of these parts to obtain DNA template is now underway. In the next experiments, preparation and other nucleothioglucosides such as CMP-NeuNAc and G-Glc, and glycosylation of these glycosyl donors as well as the aforementioned glycosides, T-Gal and A-GlcNAc, with glycosyl acceptors in the presence of DNA-template will be examined. Less

本项目的目标是开发新的方法学，用于在DNA模板上合成寡糖。我们假设，具有核碱基的糖基供体将由于互补碱基对之间的氢键而在DNA模板上对齐，并且糖基化将在添加糖基供体的活化剂后进行，从而导致寡糖的靶序列的选择性合成。这也为直接将DNA基因序列转化为寡糖序列提供了一个新的思路。为此，我们决定设计合成核苷硫代糖苷，即通过共价键与核碱基连接的硫代糖苷，因为硫代糖苷稳定且可被特定的活化剂活化，因此在寡糖合成的许多实例中用作糖基供体。以溴苯为原料，经8步反应得到含胸腺嘧啶核苷（T）的苯乙酮部分，再与乙酸半乳糖酯反应得到含胸腺嘧啶核苷（T）的苯乙酮部分， ...更多信息与胸苷（T）连接的碘半乳糖苷（T-Gal）。另外，以类似的方式制备具有腺苷（A-Gal）和与A（A-GlcNAc）连接的N-乙酰基-葡糖胺的Gal。其次，T-Gal与葡萄糖衍生物的糖基化反应以较高的产率得到了所需的双糖，如Gal（β1→4）Glc，证明了核碱基连接的硫代糖苷糖基化的可能性。然而，在这些反应条件下，用具有腺苷单元的糖基受体糖基化T-Gal和用几种受体糖基化A-GlcNAc不成功，可能是因为启动子的刘易斯酸性被这些底物的腺苷部分中和。因此，我们测试了几种反应条件（活化剂、溶剂和温度），最终发现Tol-SCl和AgOTf（OTf=三氟甲磺酸酯）的组合以中等或高的化学产率得到目标二糖。现在正在进行这些部分的偶联反应以获得DNA模板。在接下来的实验中，将检查制备和其他核硫代葡萄糖苷如CMP-NeuNAc和G-Glc，以及这些糖基供体以及上述糖苷T-Gal和A-GlcNAc在DNA模板存在下与糖基受体的糖基化。少

项目成果

期刊论文数量（0）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Design and Synthesis of a Photocleavable Linker for the Isolation Device of Circulating Tumor Cells

用于循环肿瘤细胞分离装置的光裂解接头的设计与合成

DOI：
发表时间：
2011
期刊：
影响因子：
0
作者：
Shinya Ariyasu;Kengo Hanaya;Megumi Tsunoda;Misato Hoshi;Masanori Kitamura;Masanori Hayase;Ryo Abe;Shin Aoki
通讯作者：
Shin Aoki

ホームページ等亜鉛イオンなどの金属イオンに応答してシグナルが変化する<11>^B NMRプローブの設計と合成を行い、生きている細胞内の亜鉛イオン検出に成功した(In-cell NMR)。この成果(Inorganic Chemistry, 2011, 50, 11568-11580)が、"Global Medical Discovery(GMD)"サイトの" Key Scientific Article"として紹介された

我们设计并合成了一种 11^B NMR 探针，其信号会响应锌离子等金属离子而变化，并成功检测活细胞中的锌离子（细胞内 NMR）。