Structural investigations for developing the rapeutics of Altzheimer, prion, and Parkinson's disease
开发阿尔茨海默病、朊病毒和帕金森病治疗药物的结构研究
基本信息
- 批准号:13672251
- 负责人:
- 金额:$ 2.24万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2001
- 资助国家:日本
- 起止时间:2001 至 2002
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
1. In order to obtain insight how to find out oligqpeptides from the amino acid sequences of A β, PrP, and NAG, oligopeptidemediated helix stabilization of Na channel related peptides has been studied. It was found that oligopeptides should involve hydrophobic amino acids and should be interposed by such polar amino acids as lysine for stabilizing α-helices of the model peptides2. By designing various kinds of oligopeptides from the amino acid sequence of A β, interactions between oligopeptides and Aβ have been studied. Among the oligopeptides studied, only Ac-ELVFFAKK-NH_2 was found to increase β-sheet content and accelerate amyloid fibril formation3. I have selected PrP(129-154) and PrP(192-213) from PrP and studied interactions with the oligopeptides designed from those peptides. Ac-EFGNK-NH_2 and Ac-EYYEK-NH_2 stabilized α-helices of PrP(129-154), but every oligopeptides studied destabilized α-helix of PrP(192-213)4. The peptide Ac-ETVK-NH_2 increased the β-sheet content of NAG in water and accelerated amyloid fibril formation5. If an oligopeptide involves a fragment of amyloidogenic proteins and destabilizes their α-helices, the peptide could be a trigger to initiate amyloid diseases
1. 为了深入了解如何从A β、PrP和NAG的氨基酸序列中发现寡肽,我们研究了寡肽介导的Na通道相关肽的螺旋稳定。研究发现,寡肽应该包含疏水氨基酸,并应由赖氨酸等极性氨基酸介入,以稳定模型肽的α-螺旋2。通过从Aβ的氨基酸序列设计各种寡肽,研究了寡肽与Aβ的相互作用。在研究的寡肽中,只有Ac-ELVFFAKK-NH_2能增加β-sheet的含量,加速淀粉样纤维的形成3。我从PrP中选择了PrP(129-154)和PrP(192-213),并研究了它们与这些肽设计的寡肽的相互作用。Ac-EFGNK-NH_2和Ac-EYYEK-NH_2稳定了PrP的α-螺旋(129-154),但每个寡肽都破坏了PrP的α-螺旋(192-213)4。肽Ac-ETVK-NH_2增加了NAG在水中β-片的含量,加速了淀粉样纤维的形成5。如果寡肽涉及淀粉样蛋白片段并破坏其α-螺旋的稳定性,则该肽可能是引发淀粉样蛋白疾病的触发器
项目成果
期刊论文数量(5)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Yoshitaka Maeda: "Oligopeptide-mediated helix stabilization of model peptides in aqueous solution"J. Peptide Sci.. 9・2. 106-113 (2003)
前田义隆:“水溶液中模型肽的寡肽介导的螺旋稳定性”J. Peptide Sci.. 9・2(2003)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yoshitaka Maeda: "Helix-stabilizing effects of the pentapeptide KIFMK and its related Peptides on the sodium channel inactivation gate peptides"J.Peptide Res.. 58・5. 413-423 (2001)
前田义隆:“五肽 KIFMK 及其相关肽对钠通道失活门肽的螺旋稳定作用”J.Peptide Res.. 58・5(2001)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Y. Kuroda, Y. Maeda, S. Sawa, K. Shibata, K. Miyamoto, and T. Nakagawa: "Effects of detergents on the secondary structures of prion piotein peptides as studied by CD spectroscopy"J. Peptide Sci.. 9(4). 212-220 (2003)
Y. Kuroda、Y. Maeda、S. Sawa、K. Shibata、K. Miyamoto 和 T. Nakakawa:“通过 CD 光谱研究去垢剂对朊蛋白肽二级结构的影响”J。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Yoshihiro Kuroda: "Effects of detergents on the secondary structures of prion protein peptides as studied by CD spectroscopy"J. Peptide Sci.. 9(印刷中). (2003)
Yoshihiro Kuroda:“通过 CD 光谱研究去垢剂对朊病毒蛋白肽二级结构的影响”J. Peptide Sci. 9(出版中)。
- DOI:
- 发表时间:
- 期刊:
- 影响因子:0
- 作者:
- 通讯作者:
Kazuhide Miyamoto: "Solution structures of the cytoplasmic linkers between segments S4 and S5 (S4-S5) in domains III and IV of human brain sodium Channels in SDS micelles"J. Peptide Res.. 58・3. 193-203 (2001)
Kazuhide Miyamoto:“SDS 胶束中人脑钠通道的结构域 III 和 IV 中的片段 S4 和 S5 之间的细胞质连接体的溶液结构”J. 58・3 (2001)。
- 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 }}
KURODA Yoshihiro其他文献
KURODA 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('KURODA Yoshihiro', 18)}}的其他基金
High quality haptic interaction with a soft body for remote collaboration
与软体进行高质量触觉交互,实现远程协作
- 批准号:
24700117 - 财政年份:2012
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
The inhibitory potency of peptides derived from autophosphorylation sites of receptor tyrosine kinase in a non-ATP-competitive mechanism on tumor cells.
源自受体酪氨酸激酶自磷酸化位点的肽以非 ATP 竞争性机制对肿瘤细胞的抑制效力。
- 批准号:
22590076 - 财政年份:2010
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Studies on inhibitors for epidermal growth factor receptor based on oligopeptides which imitated pseudosubstrates
基于模拟假底物寡肽的表皮生长因子受体抑制剂的研究
- 批准号:
18590032 - 财政年份:2006
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Mechanisms of suppression of insulin signaling by Na channel blockers
Na通道阻滞剂抑制胰岛素信号传导的机制
- 批准号:
15590040 - 财政年份:2003
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Theoretical Study of Anomalous Metallic Propertices of Strongly Coupled Electrons.
强耦合电子反常金属性质的理论研究。
- 批准号:
12640343 - 财政年份:2000
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Structural investiga tions for developing therapeutics of functional disorders due to the sodium channel
开发钠通道功能障碍疗法的结构研究
- 批准号:
09470493 - 财政年份:1997
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
Theoretical Study of Transport Phenomena based on Mori Formula
基于Mori公式的输运现象理论研究
- 批准号:
08640483 - 财政年份:1996
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Theoretical Study on Charge Fluctuation in Strongly Correlated Electrons
强相关电子电荷涨落的理论研究
- 批准号:
03640306 - 财政年份:1991
- 资助金额:
$ 2.24万 - 项目类别:
Grant-in-Aid for General Scientific Research (C)
相似海外基金
Advancement of Prion Protein-Lowering Divalent siRNA Therapy for Prion Disease
朊病毒蛋白降低二价 siRNA 治疗朊病毒病的进展
- 批准号:
10721465 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Measuring neural replay using magnetoencephalography (MEG); use as a biomarker in human prion disease
使用脑磁图(MEG)测量神经重放;
- 批准号:
MR/X019586/1 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Fellowship
Activation of Neuronal Degradative Pathways to Ameliorate Prion Disease
激活神经元降解途径以改善朊病毒病
- 批准号:
10855708 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Therapeutic editing to lower PrP in prion disease: Administrative Core
降低朊病毒病中 PrP 的治疗性编辑:管理核心
- 批准号:
10669492 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Therapeutic Editing to Lower PrP in Prion Disease
降低朊病毒病中 PrP 的治疗性编辑
- 批准号:
10669491 - 财政年份:2023
- 资助金额:
$ 2.24万 - 项目类别:
Conformational properties of misfolded protein aggregates in cases involving the co-occurrence of prion disease and Alzehimer's disease or prion disease and CTE
涉及朊病毒病和阿尔茨海默病或朊病毒病和 CTE 同时发生的情况下错误折叠蛋白聚集体的构象特性
- 批准号:
10682584 - 财政年份:2022
- 资助金额:
$ 2.24万 - 项目类别:
Conformational properties of misfolded protein aggregates in cases involving the co-occurrence of prion disease and Alzehimer's disease or prion disease and CTE
朊病毒病和阿尔茨海默病或朊病毒病和 CTE 同时发生的情况下错误折叠蛋白聚集体的构象特性
- 批准号:
10664201 - 财政年份:2022
- 资助金额:
$ 2.24万 - 项目类别:
How substrate dosage drives prion disease kinetics
底物剂量如何驱动朊病毒疾病动力学
- 批准号:
10344724 - 财政年份:2021
- 资助金额:
$ 2.24万 - 项目类别:
Development of Prion Protein-Lowering Divalent siRNA Therapy for Prion Disease
开发针对朊病毒病的降低朊病毒蛋白的二价 siRNA 疗法
- 批准号:
10549815 - 财政年份:2021
- 资助金额:
$ 2.24万 - 项目类别: