New Amphiphillic Dendrimers for Encapsulation and Release
用于封装和释放的新型两亲性树枝状聚合物
基本信息
- 批准号:8325533
- 负责人:
- 金额:$ 30.38万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2003
- 资助国家:美国
- 起止时间:2003-03-01 至 2015-08-31
- 项目状态:已结题
- 来源:
- 关键词:AddressAreaBackBindingBiologicalBiological ProcessCell CommunicationCell physiologyCell surfaceCellsChemicalsCustomDendrimersDevelopmentElectron MicroscopyEncapsulatedEnzymesEquilibriumEventFibroblast Growth FactorFive-Year PlansFluorescence SpectroscopyFundingGrantHeparinInorganic SulfatesLigandsLocationMeasurementModificationMolecularMorphologyNatureOutcomePharmaceutical PreparationsPhasePolymersPolysaccharidesPropertyProteinsReactionReceptor Protein-Tyrosine KinasesReportingResearchSignal TransductionSolutionsSpecificityStimulusStructureSystemThermodynamicsUnspecified or Sulfate Ion SulfatesWaterabsorptionaqueousbasecontrolled releasedesigndriving forcehuman diseaseinterestlight scatteringmacromoleculenovel strategiesprotein protein interactionreceptorresponsescaffold
项目摘要
DESCRIPTION (provided by applicant): This proposal describes the design and development of versatile amphiphilic dendrimer-based supramolecular assemblies that disassemble in response to specific proteins as stimuli. Assembly and disassembly of macromolecules in response to a signal (or a stimulus) is an important component of most biological functions in Nature. For example, it has been shown that heparin sulfate (a natural polysaccharide) acts as the key scaffold for assembling fibroblast growth factors and transmembrane tyrosine kinase receptors that are important in several cellular processes, including cell-cell communication. Similarly, there are recent examples of receptor clustering on cell surfaces in response to artificial polyvalent ligand scaffolds. While these are examples of proteins responding to polymers, we ask here 'could we use specific proteins as signals to assemble or disassemble the supramolecular structures based on polymeric systems (more specifically dendrimers)?' This is obviously a daunting challenge. A reasonable first step towards addressing the question is to obtain a better understanding about the structural factors that control the assembly/disassembly events in response to the concentration of a specific protein. Developing such a fundamental structure-property relationship with custom-designed supramolecular assemblies could have implications in a variety of areas. For example, these assemblies could find use in controlled release applications, where the release of sequestered guest molecules (drugs) from the assembly is controlled by a stimulus. While there have been a number of reports on stimuli-responsive supramolecular assemblies, studies that use proteins as the stimuli are very limited.26,27 Exploring protein-sensitive delivery vehicles is interesting, since most of the human diseases are based on protein imbalances. The structural requirements for achieving control over these assembly/disassembly events are quite stringent. This proposal describes the first, concerted approach to achieve controlled disassembly of dendrimer based amphiphilic assemblies in response to a specific protein stimulus. We take two complementary approaches to disassemble the dendrimer assemblies through interaction with proteins: (i) where the proteins induce a covalent modification of the functionalities of the dendrimers; (ii) where the protein non-covalently binds to specific ligand functionalities in the dendrimer. Both of these approaches are backed up by significant preliminary results.
描述(由申请人提供):该提案描述了基于多功能两亲性树枝状聚合物的超分子组装体的设计和开发,该组装体响应于作为刺激的特定蛋白质而分解。大分子响应信号(或刺激)的组装和拆卸是自然界中大多数生物功能的重要组成部分。例如,已经显示硫酸肝素(一种天然多糖)充当组装成纤维细胞生长因子和跨膜酪氨酸激酶受体的关键支架,所述成纤维细胞生长因子和跨膜酪氨酸激酶受体在包括细胞-细胞通信的若干细胞过程中是重要的。类似地,最近有响应于人工多价配体支架的细胞表面上的受体聚集的例子。虽然这些是蛋白质对聚合物反应的例子,但我们在这里问“我们能否使用特定的蛋白质作为信号来组装或分解基于聚合物系统(更具体地说是树枝状聚合物)的超分子结构?“这显然是一个艰巨的挑战。解决这个问题的合理的第一步是更好地了解控制特定蛋白质浓度的组装/拆卸事件的结构因素。开发这样一个基本的结构与性质的关系与定制设计的超分子组装可能会在各个领域的影响。例如,这些组件可用于控释应用,其中螯合的客体分子(药物)从组件的释放受刺激控制。虽然有一些关于刺激响应性超分子组装体的报告,但使用蛋白质作为刺激物的研究非常有限。26,27探索蛋白质敏感的递送载体是有趣的,因为大多数人类疾病都是基于蛋白质失衡。实现对这些组装/拆卸事件的控制的结构要求是相当严格的。该提案描述了第一个,协调一致的方法来实现基于树状聚合物的两亲性组件响应于特定的蛋白质刺激的受控拆卸。我们采取两种互补的方法通过与蛋白质的相互作用来分解树枝状聚合物组装体:(i)其中蛋白质诱导树枝状聚合物的官能团的共价修饰;(ii)其中蛋白质非共价结合到树枝状聚合物中的特定配体官能团。这两种方法都得到了重要的初步结果的支持。
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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Sankaran Thayumanavan其他文献
Sankaran Thayumanavan的其他文献
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{{ truncateString('Sankaran Thayumanavan', 18)}}的其他基金
Protein-Induced Self-Assembly and Disassembly of Nanostructures Based on Oligo
基于Oligo的蛋白质诱导纳米结构自组装和分解
- 批准号:
10581638 - 财政年份:2020
- 资助金额:
$ 30.38万 - 项目类别:
Protein-Induced Self-Assembly and Disassembly of Nanostructures Based on Oligo
基于Oligo的蛋白质诱导纳米结构自组装和分解
- 批准号:
10377917 - 财政年份:2020
- 资助金额:
$ 30.38万 - 项目类别:
Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures
用于检测复杂混合物中生物标志物的超分子组件
- 批准号:
8504510 - 财政年份:2013
- 资助金额:
$ 30.38万 - 项目类别:
Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures
用于检测复杂混合物中生物标志物的超分子组件
- 批准号:
8827712 - 财政年份:2013
- 资助金额:
$ 30.38万 - 项目类别:
Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures
用于检测复杂混合物中生物标志物的超分子组件
- 批准号:
8634074 - 财政年份:2013
- 资助金额:
$ 30.38万 - 项目类别:
Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures
用于检测复杂混合物中生物标志物的超分子组件
- 批准号:
9039005 - 财政年份:2013
- 资助金额:
$ 30.38万 - 项目类别:
Supramolecular Assemblies for Detecting Biomarkers in Complex Mixtures
用于检测复杂混合物中生物标志物的超分子组件
- 批准号:
9274508 - 财政年份:2013
- 资助金额:
$ 30.38万 - 项目类别:
New Amphiphilic Dendrimers for Encapsulation and Release
用于封装和释放的新型两亲性树枝状聚合物
- 批准号:
7028279 - 财政年份:2003
- 资助金额:
$ 30.38万 - 项目类别:
New Amphiphilic Dendrimers for Encapsulation and Release
用于封装和释放的新型两亲性树枝状聚合物
- 批准号:
7656056 - 财政年份:2003
- 资助金额:
$ 30.38万 - 项目类别:
New Amphiphilic Dendrimers for Encapsulation and Release
用于封装和释放的新型两亲性树枝状聚合物
- 批准号:
6856530 - 财政年份:2003
- 资助金额:
$ 30.38万 - 项目类别:
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