Basic Research for the Creation of Artificial Nucleic Acids and Related Biomolecules with Useful Functions
创造具有有用功能的人工核酸和相关生物分子的基础研究
基本信息
- 批准号:11101001
- 负责人:
- 金额:$ 112.9万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Specially Promoted Research
- 财政年份:1999
- 资助国家:日本
- 起止时间:1999 至 2001
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
Hayakawa has developed efficient solid-phase synthesis of DNA and RNA oligomers via the phosphoramidite method using an acid/azole complex as the promoter. He has also invented a novel phosphoramidite method with molecular sieves as a moisture scavenger, allowing the solution-phase preparation of short oligonucleotides by the use of stoichiometric amounts of starting materials and a promoter. These new approaches have allowed highly efficient synthesis of biologically attractive/important substances such as CMP-Neu5Ac, 2-5A core, c(GpGp), DNA-peptide conjugates, and oligodeoxyribonucleotides with S-acetyl-2-thioethyl triester backbone. Makino has studied to elucidate unsolved nucleic acids structures and its relevance to biological functions. He (1) has established complete mechanisms for all the base damage by nitric oxide and their relevance to cancer and cell death, (2) has found varied isomeric structures of i-motif of C-repeat in human telomere and suggested its relationship with cancer and cell death, (3) has elucidated the relationship between the chirality in phosphorothioate antisenses and their target DNA and RNA recognition ability, and (4) has developed the novel method for peptide library for given base sequences. Sekine has found that a serious side reaction associated with oligonucleotide synthesis in the H-phosphonate approach occurs owing to an intramolecular attack of the 5'-terminal hydroxyl group of the growing chain on the closest internucleotidic phosphoryl group. Based on this finding, an improved H-phosphonate approach using active ester intermediates has been developed. The "proton-block method" as a new strategy for the synthesis of DNA fragments without base protection and post-treatment has been also explored. This strategy was utilized for an innovative route to N-acylated DNA fragments which have proved to have sufficient base-pairing ability.
Hayakawa开发了一种高效的固相合成DNA和RNA低聚物的方法,采用磷酸/唑配合物作为启动子。他还发明了一种新的磷酸酰胺方法,用分子筛作为除湿剂,通过使用化学计量量的起始材料和促进剂,可以在溶液中制备短的寡核苷酸。这些新方法允许高效合成具有生物吸引力/重要的物质,如CMP-Neu5Ac, 2-5A核心,c(GpGp), dna肽偶联物和具有s -乙酰-2-硫乙基三酯骨架的寡脱氧核糖核苷酸。牧野一直致力于阐明未解决的核酸结构及其与生物功能的相关性。他(1)建立了一氧化氮对所有碱基损伤的完整机制及其与癌症和细胞死亡的相关性;(2)发现了人类端粒中C-repeat i-motif的不同异构体结构,并提出了其与癌症和细胞死亡的关系;(3)阐明了硫代反义的手性与其靶DNA和RNA识别能力的关系;(4)开发了针对给定碱基序列的肽库的新方法。Sekine发现,在h -膦酸盐方法中,与寡核苷酸合成相关的严重副反应是由于生长链的5'端羟基在最近的核间磷酸基上受到分子内攻击。基于这一发现,利用活性酯中间体开发了一种改进的h -膦酸盐方法。“质子块法”作为一种无需碱基保护和后处理的DNA片段合成新策略也得到了探索。这一策略被用于一条通往n -酰化DNA片段的创新途径,已被证明具有足够的碱基配对能力。
项目成果
期刊论文数量(261)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
M.Sekine: "Total Synthesis of Agrocin 84 and Phosmidosine as Naturally Occurring Nuycleotidic Antibiotics Having P-N Bond Linkages"J. Org. Synth. Chem. Jpn.. 59. 1109-1120 (2001)
M.Sekine:“具有 P-N 键连接的天然核苷酸抗生素 Agrocin 84 和 Phosmidosine 的全合成”J。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
M.Sekine: "N-Glycosylation"Glycoscience-Chemistry and Chemical biolog I, Reid, B.Fraser, Tatuka, K., Thiem, J.Eds.Medio, Berlin. 673-690
M.Sekine:“N-糖基化”糖科学-化学和化学生物学I,Reid,B.Fraser,Tatuka,K.,Thiem,J.Eds.Medio,柏林。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sakakura,A.: "A Novel Synthesis of Oligonucleotide-Peptide Conjugates with a Base-Labile Phosphate Linker between the Two Components According to the Allyl-Protected Phosphoramidite Strategy"Tetrrahedron. 56. 4427-4435 (2000)
Sakakura,A.:“根据烯丙基保护的亚磷酰胺策略,在两个组分之间具有碱不稳定磷酸酯连接物的寡核苷酸-肽缀合物的新合成”四面体。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Kataoka,M.: "Ethyl (methyl) dioxirane as an Efficient Reagent for the Oxidation of Nucleoside Phosphites into Phosphates under Non-basic, Anhydrous Conditions"Org.Lett.. 3(in press).
Kataoka,M.:“乙基(甲基)二环氧乙烷作为在非碱性、无水条件下将核苷亚磷酸盐氧化成磷酸盐的有效试剂”Org.Lett.. 3(出版中)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Sekine,M.: "Synthesis and Properties of Oligonucleotides Having a Phosphorus Chiral Center by Incorporation of Conformationally Rigid 5'-Cyclouridylic Acid Derivatives"J.Org.Chem.. 65. 6515-6524 (2000)
Sekine,M.:“通过掺入构象刚性 5-环尿苷酸衍生物来合成具有磷手性中心的寡核苷酸和性质”J.Org.Chem.. 65. 6515-6524 (2000)
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
HAYAKAWA Yoshihiro其他文献
HAYAKAWA Yoshihiro的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('HAYAKAWA Yoshihiro', 18)}}的其他基金
Investigation for NK cell subset homeostasis and function in tumor mocroenvironment
肿瘤微环境中NK细胞亚群稳态和功能的研究
- 批准号:
23701073 - 财政年份:2011
- 资助金额:
$ 112.9万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Platform Development of Optimization System based on Active Artificial Neural Network
基于主动人工神经网络的优化系统平台开发
- 批准号:
23500291 - 财政年份:2011
- 资助金额:
$ 112.9万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Role of Asialoglycoprotein receptor in tumor microenvironment
去唾液酸糖蛋白受体在肿瘤微环境中的作用
- 批准号:
21890044 - 财政年份:2009
- 资助金额:
$ 112.9万 - 项目类别:
Grant-in-Aid for Research Activity Start-up
Toward development of novel medicines for bacterial infection : Search of biological functions and elucidation of mechanism on occurrence of the functions of c-di-GMP and related compounds
致力于细菌感染新药的开发:c-di-GMP及相关化合物的生物学功能探索及功能发生机制的阐明
- 批准号:
20350076 - 财政年份:2008
- 资助金额:
$ 112.9万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Creation and efficient synthesis of nucleic acids and related compounds with valuable functionality and bioactivity
具有有价值的功能和生物活性的核酸和相关化合物的创建和有效合成
- 批准号:
16350086 - 财政年份:2004
- 资助金额:
$ 112.9万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Enantioselective Synthesis of Unsymmetrically-Substituted Organophosphorus Compounds with Stereogenic Phosphorus Atoms
具有立体磷原子的不对称取代有机磷化合物的对映选择性合成
- 批准号:
08454200 - 财政年份:1996
- 资助金额:
$ 112.9万 - 项目类别:
Grant-in-Aid for Scientific Research (B)