Using deep-cavity cavitands to study supramolecular chemistry in water
利用深腔空配体研究水中的超分子化学
基本信息
- 批准号:8627614
- 负责人:
- 金额:$ 28.29万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2012
- 资助国家:美国
- 起止时间:2012-06-01 至 2016-02-29
- 项目状态:已结题
- 来源:
- 关键词:AffinityAgeAnionsBindingBiological ModelsCalorimetryChemistryComplexComputer SimulationDataDocumentationEmployee StrikesEventGoalsInorganic SulfatesIonsLeadLifeModelingModusMolecularNMR SpectroscopyOilsPerchloratesPrecipitationPropertyProteinsResearchSaltsScienceSeriesShapesSodium ChlorideSolubilitySolutionsSolventsStructureSurface TensionThermodynamicsTitrationsUnspecified or Sulfate Ion SulfatesViscosityWaterWorkX-Ray Crystallographyaqueousbasecavitanddriving forcemathematical modelmolecular scaleprogramsprotein structureresearch studysolute
项目摘要
DESCRIPTION (provided by applicant): The goal of this program of research is to contribute to Science's understanding of the Hydrophobic Effect. Water, the 'solvent of life' has a profound influence on the structure and assembly of proteins and other biomolecules, yet there are still many unknowns regarding the modus operandi of the Hydrophobic Effect. For example, our understanding of the Hofmeister Effect - why some salts (kosmotropes) decrease the solubility of organic solutes whilst others (chaotropes) increase solubility - is poorly understood; even though the phenomenon was first described by Hofmeister over 120 years ago. In studying the formation of a host-guest complex driven by the hydrophobic effect, we have observed that the strength of complexation varies as a function of co-solute salts, in a manner paralleling the ability of salts to induce either precipitation or solubilization of proteins. Thus, kosmotropic sats cause an apparent decrease in the solubility of the host-guest pair and lead to an enhancement of the binding affinity, whilst chaotropes have the opposite effect. Using a combination of Isothermal Titration Calorimetry (ITC) and Nuclear Magnetic Resonance (NMR) spectroscopy, we have traced the ability of chaotropes to weaken binding to the fact that anions have a surprisingly strong affinity for hydrophobic concavity. In other words, the reduced affinity between host and guest occurs because chaotropic anions compete with the hydrophobic guest for binding to the host. This is the first observation of anions binding to hydrophobic concavity. Furthermore, ITC and NMR spectroscopy allows the accurate determination of the thermodynamics of host-guest and host-anion binding. As a result, the data we are gathering is allowing us to build the first molecular-scale models of the Hofmeister Effect. The major hypothesis behind this program of study is that anion binding to concavity is one of the major driving forces behind the observation that chaotropes break up protein quaternary and tertiary structure to form the molten-globule state. To build on this idea, this proposal describes experiments to probe the thermodynamics of 1:1 complexation of organic guests to a series of cavitand hosts. These studies will utilize a combination of ITC, NMR, spectroscopy, in silico work, and X-ray crystallography, to examine how co solutes salts influence these binding events. This data will be used to build the first thermodynamic models of the Hofmeister Effect at the molecular level, and has the potential to unify current models of the Hofmeister Effect based on bulk properties such as solubility, viscosity, and surface tension.
描述(由申请人提供):本研究项目的目标是促进科学对疏水效应的理解。水,作为“生命的溶剂”,对蛋白质和其他生物分子的结构和组装有着深远的影响,但关于疏水效应的运作方式仍有许多未知之处。例如,我们对霍夫迈斯特效应的理解——为什么有些盐(宇宙异色盐)会降低有机溶质的溶解度,而另一些盐(混沌异色盐)会增加溶解度——知之甚少;尽管这种现象最早是由霍夫迈斯特在120多年前描述的。在研究由疏水效应驱动的主-客体络合物的形成时,我们观察到络合的强度随共溶质盐的作用而变化,其方式与盐诱导蛋白质沉淀或增溶的能力相似。因此,共向卫星导致主-客体对溶解度的明显降低,并导致结合亲和力的增强,而混沌卫星则具有相反的效果。使用等温滴定量热法(ITC)和核磁共振(NMR)光谱的结合,我们已经追踪了混沌的能力削弱结合的事实,阴离子对疏水凹具有惊人的强亲和力。换句话说,宿主和客体之间的亲和力降低是因为向乱性阴离子与疏水性客体竞争与宿主的结合。这是首次观察到阴离子与疏水凹的结合。此外,ITC和核磁共振光谱可以准确地确定主-客体和主-阴离子结合的热力学。因此,我们正在收集的数据使我们能够建立霍夫迈斯特效应的第一个分子尺度模型。这个研究项目背后的主要假设是,阴离子与凹度的结合是观察到混沌物破坏蛋白质的四级和三级结构以形成熔融球状状态的主要驱动力之一。为了建立这一想法,本提案描述了探索有机客体与一系列空腔和宿主1:1络合的热力学实验。这些研究将结合ITC、核磁共振、光谱学、硅工作和x射线晶体学来研究co溶质盐如何影响这些结合事件。这些数据将用于在分子水平上建立霍夫迈斯特效应的第一个热力学模型,并有可能统一目前基于溶解度、粘度和表面张力等体积性质的霍夫迈斯特效应模型。
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 }}
BRUCE C GIBB其他文献
BRUCE C GIBB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('BRUCE C GIBB', 18)}}的其他基金
Ion-Ion Interactions and the Reverse Hofmeister Effect
离子-离子相互作用和逆霍夫迈斯特效应
- 批准号:
10202645 - 财政年份:2018
- 资助金额:
$ 28.29万 - 项目类别:
Using deep-cavity cavitands to study supramolecular chemistry in water
利用深腔空配体研究水中的超分子化学
- 批准号:
8477215 - 财政年份:2012
- 资助金额:
$ 28.29万 - 项目类别:
Using deep-cavity cavitands to study supramolecular chemistry in water
利用深腔空配体研究水中的超分子化学
- 批准号:
8258409 - 财政年份:2012
- 资助金额:
$ 28.29万 - 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
- 批准号:
7171524 - 财政年份:2006
- 资助金额:
$ 28.29万 - 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
- 批准号:
7575601 - 财政年份:2006
- 资助金额:
$ 28.29万 - 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
- 批准号:
7760945 - 财政年份:2006
- 资助金额:
$ 28.29万 - 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
- 批准号:
7032211 - 财政年份:2006
- 资助金额:
$ 28.29万 - 项目类别:
Capsular Assemblies Driven by the Hydrophobic Effect
由疏水效应驱动的胶囊组件
- 批准号:
7343269 - 财政年份:2006
- 资助金额:
$ 28.29万 - 项目类别:
相似国自然基金
靶向递送一氧化碳调控AGE-RAGE级联反应促进糖尿病创面愈合研究
- 批准号:JCZRQN202500010
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
对香豆酸抑制AGE-RAGE-Ang-1通路改善海马血管生成障碍发挥抗阿尔兹海默病作用
- 批准号:2025JJ70209
- 批准年份:2025
- 资助金额:0.0 万元
- 项目类别:省市级项目
AGE-RAGE通路调控慢性胰腺炎纤维化进程的作用及分子机制
- 批准号:
- 批准年份:2024
- 资助金额:0 万元
- 项目类别:面上项目
甜茶抑制AGE-RAGE通路增强突触可塑性改善小鼠抑郁样行为
- 批准号:2023JJ50274
- 批准年份:2023
- 资助金额:0.0 万元
- 项目类别:省市级项目
蒙药额尔敦-乌日勒基础方调控AGE-RAGE信号通路改善术后认知功能障碍研究
- 批准号:
- 批准年份:2022
- 资助金额:33 万元
- 项目类别:地区科学基金项目
补肾健脾祛瘀方调控AGE/RAGE信号通路在再生障碍性贫血骨髓间充质干细胞功能受损的作用与机制研究
- 批准号:
- 批准年份:2022
- 资助金额:52 万元
- 项目类别:面上项目
LncRNA GAS5在2型糖尿病动脉粥样硬化中对AGE-RAGE 信号通路上相关基因的调控作用及机制研究
- 批准号:n/a
- 批准年份:2022
- 资助金额:10.0 万元
- 项目类别:省市级项目
围绕GLP1-Arginine-AGE/RAGE轴构建探针组学方法探索大柴胡汤异病同治的效应机制
- 批准号:81973577
- 批准年份:2019
- 资助金额:55.0 万元
- 项目类别:面上项目
AGE/RAGE通路microRNA编码基因多态性与2型糖尿病并发冠心病的关联研究
- 批准号:81602908
- 批准年份:2016
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
高血糖激活滑膜AGE-RAGE-PKC轴致骨关节炎易感的机制研究
- 批准号:81501928
- 批准年份:2015
- 资助金额:18.0 万元
- 项目类别:青年科学基金项目
相似海外基金
PROTEMO: Emotional Dynamics Of Protective Policies In An Age Of Insecurity
PROTEMO:不安全时代保护政策的情绪动态
- 批准号:
10108433 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
EU-Funded
The role of dietary and blood proteins in the prevention and development of major age-related diseases
膳食和血液蛋白在预防和发展主要与年龄相关的疾病中的作用
- 批准号:
MR/X032809/1 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Fellowship
Atomic Anxiety in the New Nuclear Age: How Can Arms Control and Disarmament Reduce the Risk of Nuclear War?
新核时代的原子焦虑:军控与裁军如何降低核战争风险?
- 批准号:
MR/X034690/1 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Fellowship
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341426 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Continuing Grant
Collaborative Research: Resolving the LGM ventilation age conundrum: New radiocarbon records from high sedimentation rate sites in the deep western Pacific
合作研究:解决LGM通风年龄难题:西太平洋深部高沉降率地点的新放射性碳记录
- 批准号:
2341424 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Continuing Grant
Doctoral Dissertation Research: Effects of age of acquisition in emerging sign languages
博士论文研究:新兴手语习得年龄的影响
- 批准号:
2335955 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Standard Grant
The economics of (mis)information in the age of social media
社交媒体时代(错误)信息的经济学
- 批准号:
DP240103257 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Discovery Projects
How age & sex impact the transcriptional control of mammalian muscle growth
你多大
- 批准号:
DP240100408 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Discovery Projects
Supporting teachers and teaching in the age of Artificial Intelligence
支持人工智能时代的教师和教学
- 批准号:
DP240100111 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Discovery Projects
Enhancing Wahkohtowin (Kinship beyond the immediate family) Community-based models of care to reach and support Indigenous and racialized women of reproductive age and pregnant women in Canada for the prevention of congenital syphilis
加强 Wahkohtowin(直系亲属以外的亲属关系)以社区为基础的护理模式,以接触和支持加拿大的土著和种族育龄妇女以及孕妇,预防先天梅毒
- 批准号:
502786 - 财政年份:2024
- 资助金额:
$ 28.29万 - 项目类别:
Directed Grant