Structure and Dynamics of Phospholipids in Micelles
胶束中磷脂的结构和动力学
基本信息
- 批准号:7131836
- 负责人:
- 金额:$ 17.92万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2006
- 资助国家:美国
- 起止时间:2006-07-01 至 2010-06-30
- 项目状态:已结题
- 来源:
- 关键词:alkyl groupchemical synthesiselectron spin resonance spectroscopyenzyme activityfluorescence resonance energy transferhydrolysislipid structuremathematicsmicellesminority institution research supportmolecular dynamicsphospholipase Cphospholipidsphysical chemical interactionphysical propertytime resolved datawater
项目摘要
Phospholipids provide the matrix of all biological membranes, and their metabolic degradation, transportation
and participation in membrane remodeling occur.in micelles. In order to elucidate the mechanisms of these
processes and to facilitate the use of phospholipid containing micelles as reaction media their structure and
physical properties must be delineated. The long term goal of the proposed research is to develop wellcharacterized
micellar substrates for the study of lipolytic enzymes. Phospholipases are involved in
metabolic degradation of phospholipids; they also participate in vitally important physiological processes
including signal transduction, platelet aggregation, cardiac contraction and excitation, and prostaglandin
biosynthesis. In these events water soluble lipolytic enzymes act on water insoluble substrates that are
organized in supramolecular aggregates (e.g., mixed micelles). Elucidation of the physicochemical properties
of the lipid-water interface and its effect on phospholipase catalysis will advance the level of understanding
the mechanism of action of these enzymes.
The working hypothesis is that by delineating the contributions of the micellar components to the
physicochemical properties of the lipid-water interface one will be able to design micelles with targeted
physicochemical properties. To test this hypothesis a newly developed spin exchange EPR technique will be
used in conjunction with time-resolved fluorescence quenching measurements. 1) Site directed spin
labelings, and fluorescent reporter groups will be used to determine the contribution of the alkyl chain to the
properties of the micelle, 2) the physicochemical parameters of the polar shell will be determined using the
spin probe di-tert.-butyl nitroxide (DTBN), 3) inter-phase solute exchange between the micelles and water
will be measured by spin label partitioning, and 4) the relationship between the properties of the lipid-water
interface and the rate of phospholipid hydrolysis will be established using a series of secretory
phospholipase enzymes. Should the new EPR method prove to be successful in characterizing the mixed
micelles here studied, it will open the possibility to apply it to other more complicated supramolecular
assemblies (e.g. phospholipids-bile salt mixed micelles) and may become a general technique to
characterize micellar aggregates.
Relevance to Public Health: Micelles play an important role in biological processes, including drug delivery
and membrane function. Elucidation of their structure and properties will provide useful information toward
better understanding of membrane-dependent normal and pathological cell functions including cell signaling,
inflammation, allergy, apoptosis, as well as membrane fusion.
磷脂提供所有生物膜的基质,及其代谢降解、运输
并参与胶束中的膜重塑。为了阐明这些机制
过程并促进使用含磷脂的胶束作为反应介质、其结构和
必须描述物理特性。拟议研究的长期目标是开发特征良好的
用于研究脂肪分解酶的胶束底物。磷脂酶参与
磷脂的代谢降解;它们还参与至关重要的生理过程
包括信号转导、血小板聚集、心脏收缩和兴奋以及前列腺素
生物合成。在这些情况下,水溶性脂肪分解酶作用于水不溶性底物,这些底物是
组织成超分子聚集体(例如混合胶束)。理化性质的阐明
脂水界面及其对磷脂酶催化的影响将提高理解水平
这些酶的作用机制。
工作假设是,通过描述胶束成分对
脂质-水界面的物理化学性质将能够设计具有针对性的胶束
理化性质。为了检验这一假设,新开发的自旋交换 EPR 技术将
与时间分辨荧光猝灭测量结合使用。 1) 定点旋转
标记和荧光报告基团将用于确定烷基链对
胶束的性质,2)极性壳的物理化学参数将使用以下公式确定
自旋探针二叔丁基硝基氧 (DTBN),3) 胶束和水之间的相间溶质交换
将通过自旋标签分配来测量,4) 脂质-水特性之间的关系
将使用一系列分泌物建立界面和磷脂水解速率
磷脂酶。如果新的 EPR 方法能够成功地表征混合
这里研究的胶束,将为将其应用于其他更复杂的超分子提供可能性
组装体(例如磷脂-胆汁盐混合胶束)并可能成为一种通用技术
表征胶束聚集体。
与公共卫生的相关性:胶束在生物过程中发挥着重要作用,包括药物输送
和膜功能。阐明它们的结构和性质将为以下方面提供有用的信息:
更好地了解膜依赖性正常和病理细胞功能,包括细胞信号传导,
炎症、过敏、细胞凋亡以及膜融合。
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)
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JOSEPH HAJDU其他文献
JOSEPH HAJDU的其他文献
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{{ truncateString('JOSEPH HAJDU', 18)}}的其他基金
Phospholipid dynamics and lipolysis in membrane models
膜模型中的磷脂动力学和脂肪分解
- 批准号:
8270468 - 财政年份:2011
- 资助金额:
$ 17.92万 - 项目类别:
Phospholipid dynamics and lipolysis in membrane models
膜模型中的磷脂动力学和脂肪分解
- 批准号:
8656712 - 财政年份:2011
- 资助金额:
$ 17.92万 - 项目类别:
Phospholipid dynamics and lipolysis in membrane models
膜模型中的磷脂动力学和脂肪分解
- 批准号:
8461140 - 财政年份:2011
- 资助金额:
$ 17.92万 - 项目类别:
Phospholipid dynamics and lipolysis in membrane models
膜模型中的磷脂动力学和脂肪分解
- 批准号:
8076695 - 财政年份:2011
- 资助金额:
$ 17.92万 - 项目类别:
SYNTHESIS AND SPECTROSCOPY OF PHOSLIPID ANALOGUES
磷脂类似物的合成和光谱学
- 批准号:
6346191 - 财政年份:2000
- 资助金额:
$ 17.92万 - 项目类别:
SYNTHESIS AND SPECTROSCOPY OF PHOSLIPID ANALOGUES
磷脂类似物的合成和光谱学
- 批准号:
6204256 - 财政年份:1999
- 资助金额:
$ 17.92万 - 项目类别:
SYNTHESIS AND SPECTROSCOPY OF PHOSLIPID ANALOGUES
磷脂类似物的合成和光谱学
- 批准号:
6216637 - 财政年份:1999
- 资助金额:
$ 17.92万 - 项目类别:
SYNTHESIS AND SPECTROSCOPY OF PHOSLIPID ANALOGUES
磷脂类似物的合成和光谱学
- 批准号:
6296713 - 财政年份:1999
- 资助金额:
$ 17.92万 - 项目类别:
SYNTHESIS AND SPECTROSCOPY OF PHOSLIPID ANALOGUES
磷脂类似物的合成和光谱学
- 批准号:
6107663 - 财政年份:1998
- 资助金额:
$ 17.92万 - 项目类别:
SYNTHESIS AND SPECTROSCOPY OF PHOSLIPID ANALOGUES
磷脂类似物的合成和光谱学
- 批准号:
6240564 - 财政年份:1997
- 资助金额:
$ 17.92万 - 项目类别:
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