COMPLEX OF FPPS-PV
FPPS-PV复合体
基本信息
- 批准号:8170665
- 负责人:
- 金额:$ 0.41万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2010
- 资助国家:美国
- 起止时间:2010-07-01 至 2011-06-30
- 项目状态:已结题
- 来源:
- 关键词:AnabolismCarotenoidsCommitCommunitiesComplexComputer Retrieval of Information on Scientific Projects DatabaseComputing MethodologiesDevelopmentFundingGrantHumanInstitutionMethicillin ResistanceMusOrangesPhysical condensationProcessReactive Oxygen SpeciesResearchResearch PersonnelResistanceResourcesSourceSqualene SynthetaseStaphylococcus aureusUnited States National Institutes of HealthVirulence FactorsVirulentWorkbasedehydrosqualenedesignhypercholesterolemiainhibitor/antagonistisoprenoidkillingsneutrophilresistant strainstaphyloxanthin
项目摘要
This subproject is one of many research subprojects utilizing the
resources provided by a Center grant funded by NIH/NCRR. The subproject and
investigator (PI) may have received primary funding from another NIH source,
and thus could be represented in other CRISP entries. The institution listed is
for the Center, which is not necessarily the institution for the investigator.
We are using x-ray and computational methods to guide the development of molecules that inhibit formation of the orange carotenoid virulence factor, staphyloxanthin, in S. aureus. The first committed step in staphyloxanthin biosynthesis is the condensation of two molecules of the isoprenoid farnesyldiphosphate (FPP) to form dehydrosqualene. In recent preliminary work, we have discovered that phosphonosulfonates (human squalene synthase inhibitors which have been developed to treat hypercholesterolemia) also block staphyloxanthin biosynthesis in S. aureus, at 200 nM levels. The resulting S. aureus (L. aureus=golden) are white, non-infective in mice and are killed by neutrophils, since they have decreased defenses to reactive oxygen species (ROS). In Aim 1, we will develop more potent and selective compounds, using NMR, x-ray and computational methods to guide the design process. If successful, this work would be of importance given the increasing number of virulent, community acquired S. aureus and methicillin resistant strains which are becoming highly resistant to ROS based killing.
这个子项目是许多研究子项目中利用
资源由NIH/NCRR资助的中心拨款提供。子项目和
调查员(PI)可能从NIH的另一个来源获得了主要资金,
并因此可以在其他清晰的条目中表示。列出的机构是
该中心不一定是调查人员的机构。
我们正在使用X射线和计算方法来指导分子的开发,以抑制金黄色葡萄球菌中橙色类胡萝卜素毒力因子葡萄糖素的形成。葡黄素生物合成的第一步是类异戊二烯的法尼基二磷酸(FPP)的两个分子缩合形成脱氢角鲨烯。在最近的初步工作中,我们发现膦磺酸盐(已开发的用于治疗高胆固醇血症的人角鲨烯合成酶抑制剂)也在200 NM水平上阻止金黄色葡萄球菌中葡萄糖素的生物合成。由此产生的金黄色葡萄球菌(金黄色葡萄球菌=金黄色)是白色的,在小鼠中不具感染性,可被中性粒细胞杀死,因为它们降低了对活性氧物种(ROS)的防御能力。在目标1中,我们将开发更有效和更有选择性的化合物,使用核磁共振、X射线和计算方法来指导设计过程。如果成功,这项工作将具有重要意义,因为越来越多的毒力、社区获得的金黄色葡萄球菌和甲氧西林耐药菌株正在对基于ROS的杀戮产生高度抗药性。
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)
数据更新时间:{{ journalArticles.updateTime }}
{{
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 }}
Eric Oldfield其他文献
Eric Oldfield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('Eric Oldfield', 18)}}的其他基金
Next generation bisphosphonates for chemo- and immuno-therapy
用于化疗和免疫治疗的下一代双膦酸盐
- 批准号:
8444316 - 财政年份:2011
- 资助金额:
$ 0.41万 - 项目类别:
Next generation bisphosphonates for chemo- and immuno-therapy
用于化疗和免疫治疗的下一代双膦酸盐
- 批准号:
8627146 - 财政年份:2011
- 资助金额:
$ 0.41万 - 项目类别:
Next generation bisphosphonates for chemo- and immuno-therapy
用于化疗和免疫治疗的下一代双膦酸盐
- 批准号:
8825340 - 财政年份:2011
- 资助金额:
$ 0.41万 - 项目类别:
Next generation bisphosphonates for chemo- and immuno-therapy
用于化疗和免疫治疗的下一代双膦酸盐
- 批准号:
8085202 - 财政年份:2011
- 资助金额:
$ 0.41万 - 项目类别:
Prenyldiphosphate Synthase Inhibitors: Novel Anti-Infective Agents
异戊二烯二磷酸合酶抑制剂:新型抗感染剂
- 批准号:
7686803 - 财政年份:2002
- 资助金额:
$ 0.41万 - 项目类别:
Prenyl Synthase Inhibitors: Novel Anti-Infective Agents
异戊二烯合酶抑制剂:新型抗感染剂
- 批准号:
7984564 - 财政年份:2002
- 资助金额:
$ 0.41万 - 项目类别:
Prenyl Synthase Inhibitors: Novel Anti-Infective Agents
异戊二烯合酶抑制剂:新型抗感染剂
- 批准号:
8532682 - 财政年份:2002
- 资助金额:
$ 0.41万 - 项目类别:
相似海外基金
Elucidation of preventive mechanisms for neurodegenerative diseases through regulation of microglial function by marine carotenoids
通过海洋类胡萝卜素调节小胶质细胞功能阐明神经退行性疾病的预防机制
- 批准号:
23K14018 - 财政年份:2023
- 资助金额:
$ 0.41万 - 项目类别:
Grant-in-Aid for Early-Career Scientists
Elucidation of the novel non photochemical quenching by in vitro reconstitution of light-harvesting complex with carbonyl carotenoids.
通过体外重建具有羰基类胡萝卜素的光捕获复合物来阐明新型非光化学猝灭。
- 批准号:
23K05721 - 财政年份:2023
- 资助金额:
$ 0.41万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Theoretical Study of Singlet Fission in Carotenoids
类胡萝卜素单线态裂变的理论研究
- 批准号:
2758029 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
Studentship
Understanding the role of carotenoids in bacterial light-harvesting proteins
了解类胡萝卜素在细菌光捕获蛋白中的作用
- 批准号:
BB/W004593/1 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
Research Grant
Fullerene Assisted-Micellar Electrokinetic Chromatography of Major Carotenoids
主要类胡萝卜素的富勒烯辅助胶束电动色谱法
- 批准号:
572245-2022 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
University Undergraduate Student Research Awards
Understanding the role of carotenoids in bacterial light-harvesting proteins
了解类胡萝卜素在细菌光捕获蛋白中的作用
- 批准号:
BB/W005719/1 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
Research Grant
Examining the role of LDLR in the biodistribution of carotenoids
检查 LDLR 在类胡萝卜素生物分布中的作用
- 批准号:
10709514 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
Metabolic Engineering and Synthetic Biology approaches for sustainable and efficient production of carotenoids in yeast
在酵母中可持续高效生产类胡萝卜素的代谢工程和合成生物学方法
- 批准号:
576220-2022 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
Alliance Grants
Development and Optimization of Downstream Purification Process of LCY's Carotenoids Products
李长荣类胡萝卜素产品下游纯化工艺开发与优化
- 批准号:
556138-2020 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别:
Applied Research and Development Grants - Level 2
Examining the role of LDLR in the biodistribution of carotenoids
检查 LDLR 在类胡萝卜素生物分布中的作用
- 批准号:
10534613 - 财政年份:2022
- 资助金额:
$ 0.41万 - 项目类别: