课题基金 / 基金详情

Chemogenomic approach for elucidation and control of intracellular signal transductions

Chemogenomic approach for elucidation and control of intracellular signal transductions
阐明和控制细胞内信号转导的化学基因组学方法
批准号:
15310150
负责人:
KATO Nobuo
金额:
$9.54万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2003
资助国家:
日本
项目状态:
已结题
起止时间:
2003 至 2005

项目摘要

项目成果

KATO Nobuo的其他基金

相关文献

中文摘要
翻译
本文对一种镰刀菌型二萜苷类化合物Cotylenin(CN)的抗癌活性进行了正向化学基因组学研究,并对细胞内信号转导调节蛋白14-3-3进行了反向化学基因组学研究。所获得的结果总结如下:1. CN与干扰素α或雷帕霉素分别在卵巢癌和乳腺癌细胞上观察到显著的协同效应。通过这些联合治疗,有效地减少了小鼠异种移植瘤的生长。3α-hydroxyfusicoccin J是从产梭孢菌素(fusicoccin,FC)的真菌扁桃拟茎点霉(Phomopsis amygdali)中分离得到的一种极性同系物。该化合物可用于CN/FC类化合物抗癌活性的构效关系(SAR)研究. CN和FC对植物组织的活性相当。然而,只有CN对人髓系白血病细胞系(HL-60)具有较强的诱导分化活性。FC表现出细胞毒性。详细的SAR研究得出结论,FC的12-OH干扰活性.根据构效关系研究的结论,我们成功地合成了12-脱氧梭孢菌素衍生物,其活性与CN.5的活性相当。反向化学基因组学研究表明,CN可以与14-3-3 sigma交联作为异构体选择性方式,并加强该异构体与其伴侣磷肽的结合能力。
英文摘要
Forward chemogenomic studies for anti-cancer activity of cotylenin (CN), a fusicoccane type of diterpene glycoside, and reverse chemogenomic investigation on 14-3-3 proteins, regulatory proteins in intracellular signal transductions, have been carried out. Results obtained are summarized below :1. Significant synergistic effects of CN with interferon α or rapamicin are observed on ovary and breast cancer cells, respectively. With these combined treatment, growth of tumors were effectively reduced in xenografts on mice.2. As a polar congener of fusicoccins (FC), 3α-hydroxyfusicoccin J has been isolated from fusicoccin-producing fungus, Phomopsis amygdali. This compound was quite useful for Structure-Activity=Relationship (SAR) studies on anti-cancer activities of CN/FC class of compounds.3. CN and FC have identical activities on plant tissues. However, only CN has a strong differentiation-inducing activity of human myeloid leukemia cell line (HL-60). FC exhibits cytotoxicity instead. Detailed SAR studies lead the conclusion that the 12-OH of FC interferes the activity.4. According to the conclusion of SAR studies, we have succeeded in synthesizing 12-deoxyfusicoccin derivatives of which activities are as potent as that of CN.5. Reverse chemogenomic investigation revealed that CN can cross-link with 14-3-3 sigma as an isoform selective fashion and strength the binding ability of this isoform toward its partner phosphor-peptide.
期刊论文(16)
专著(0)
科研奖励(0)
会议论文
S.Kiyonaka, K.Sada, I.Yoshimura, S.Shinkai, N.Kato.I.Hamachi: "Semi-wet peptide/protein array using supramolecular hydrogel"Nature Materials. 3(1). 58-64 (2004)
S.Kiyonaka、K.Sada、I.Yoshimura、S.Shinkai、N.Kato.I.Hamachi:“使用超分子水凝胶的半湿肽/蛋白质阵列”《自然材料》。
DOI: --
发表时间:
期刊:
影响因子: --
作者: []
通讯作者:
Identification of (+)-Phyllocladene, (-)-Sandracopimaradiene, and (+)-Kaurene as New Fungal Metabolites from Fusicoccin-producing Phomopsis amygdali F6
鉴定 ( )-Phylloccladen、(-)-Sandracopimaradiene 和 ( )-贝壳杉烯为来自产 Fusicoccin 的扁桃拟茎点霉 F6 的新真菌代谢物
DOI: --
发表时间: 2004
期刊: Biosci.Biotechnol.Biochem. 68(7)
影响因子: --
作者: [H.Kenmoku, M.Tanaka, K.Ogiyama, N.Kato, T.Sassa]
通讯作者: T.Sassa
DOI: 10.1271/bbb.68.1786
发表时间: 2004-08-01
期刊: BIOSCIENCE BIOTECHNOLOGY AND BIOCHEMISTRY
影响因子: 1.6
作者: [Kenmoku, H, Tanaka, K, Sassa, T]
通讯作者: Sassa, T
Identification of (+)-Phyllocladene,(-)-Sandracopimaradiene, and (+)-Kaurene as New Fungal Metabolites from Fusicoccin-producing Phomopsis amygdali F6.
鉴定 ( )-Phylloccladen、(-)-Sandracopimaradiene 和 ( )-贝壳杉烯为来自产 Fusicoccin 的扁桃拟茎点霉 F6 的新真菌代谢物。
DOI: --
发表时间: 2004
期刊: Biosci.Biotechnol.Biochem. 68(7)
影响因子: --
作者: [Kenmoku, H., Tanaka, K., Ogiyama, K., Kato, N., Sassa, T.]
通讯作者: T.
13
    Electrophysiological and photometrical analysis of limbic neuronal activity in Alzheimer's mice
    • 批准号:
      17H02223
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $11.32万
    • 财政年份:
      2017
    • 负责人:
      KATO Nobuo
    • 依托单位:
    Molecular basis and its application of formaldehyde-fixing reactions in bacteria and Archaea.
    • 批准号:
      15380061
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $10.37万
    • 财政年份:
      2003
    • 负责人:
      KATO Nobuo
    • 依托单位:
    Molecular coupling required for intracellular calcium release that regulates synaptic depression
    • 批准号:
      13480266
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $8.38万
    • 财政年份:
      2001
    • 负责人:
      KATO Nobuo
    • 依托单位:
    Development of bioremediation processes under anoxic conditions using denitrifying bacteria
    • 批准号:
      12556014
    • 项目类别:
      Grant-in-Aid for Scientific Research (B)
    • 资助金额:
      $8.19万
    • 财政年份:
      2000
    • 负责人:
      KATO Nobuo
    • 依托单位: