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

该项目的目的是开发新的DNA模板上寡糖合成方法。我们假设，由于完整的碱基对和糖基供体之间的氢键，具有核碱基的糖基供体将在DNA模板上排列，从而选择性合成寡糖靶标序列。它还提供了一个新概念，用于将DNA遗传序列直接转化为橄榄糖序列。对于与理性相关的目的，我们决定设计和合成核糖苷，这些核糖苷是通过共糖苷与核苷酸酶相连的硫代糖苷，因为硫代糖苷是稳定的，因为硫糖剂是稳定的，因为他们可以通过特定的激活剂和hecy来进行供应，并且它们是在供应的范围。寡糖合成。首先，一种含有胸苷（T）的苯硫醇部分以8个步骤从溴苯制备，然后与乙酸半乳糖酯反应，以负担得起……更多的二甲酰胺与胸苷（T）（T-Gal）相关的二甲酰胺（T）（T-Gal）。此外，具有与A（A-GLCNAC）相关的腺苷（A-GAL）和N-乙酰葡萄糖胺的GAL以类似的方式制备。最近，建立了这些核乙醇葡萄糖剂的更方便的合成途径。第二，发现，用葡萄糖衍生物T-gal的糖基化给出了诸如GAL（β1→4）GLC等所需的二糖，以相当良好的产量（β1→4）GLC具有相当好的脱糖性，从而有可能具有核细胞化的糖基化thiogygogygogside。然而，在这些反应条件下，具有腺苷单位和a-GLCNAC的糖基受体对T-GAL的糖基化不成功，因为启动子的刘易斯酸度被这些底物的腺苷部分中和。因此，我们已经测试了几个反应条件（激活剂，溶液和温度），并最终发现，TOL-SCL和AGOTF（OTF = Triflate）的组合给出了中等或高的化学产量的靶二糖。现在正在进行这些部分以获得DNA模板的耦合反应。在下一个实验中，制剂和其他核乙糖苷（例如CMP-NEUNAC和G-GLC），这些糖基供体的糖基化以及在DNA-template的存在下，将使用DNA-template的糖基受体进行糖基，T-GAL和A-GLCNAC，糖基受体。较少的

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）

p53分子内の亜鉛イオン結合部位を標的とする新規阻害剤の開発

开发针对 p53 分子内锌离子结合位点的新型抑制剂

DOI：
发表时间：
2010
期刊：
影响因子：
0
作者：
大谷聡一郎;他9名
通讯作者：
他9名

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）。