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Small Molecule Self-Assembly in Aqueos Media

Aqueos 介质中的小分子自组装

基本信息

批准号：
8296561
负责人：
Jose M Rivera
金额：
$ 32.67万
依托单位：
UNIVERSITY OF PUERTO RICO RIO PIEDRAS
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：
2010-07-26 至 2014-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8296561
关键词：
Achievement Address Affinity Alzheimer&apos s Disease Area Award Bachelor&apos s Degree Binding Biochemistry Biology Cations Cell Culture Techniques Cells Cellular biology Charge Chemicals Chemistry Complex Computer Assisted Cytosine DNA DNA Binding DNA Structure Data Development Diagnostic Disease Doctor of Philosophy Education Enrollment Environment Evaluation Feedback Fluorescence Microscopy Fluorescence Resonance Energy Transfer Funding G-Quartets Generations Goals Grant Guanine Health Hispanic Americans Hispanics Human Individual Institution Island Journals Kinetics Knowledge Label Lead Left Libraries Life Ligands Master&apos s Degree Methods Molecular Molecular Models Nanostructures Natural Sciences Oligonucleotides Oncogenes Organism Peer Review Pharmaceutical Preparations Pharmacology Physics Piedra Positioning Attribute Process Productivity Property Publications Publishing Puerto Rican Puerto Rico RNA Recommendation Regulation Research Research Activity Research Personnel Resources Risk Role S Phase Science Sickle Cell Anemia Solid Source Specificity Structure Structure-Activity Relationship Students Study Section System Techniques Temperature Therapeutic Thermodynamics Time United States National Institutes of Health Universities Water Woman Work aqueous base career cellular imaging college computer science disability experience falls graduate student improved innovation member molecular assembly/self assembly molecular modeling nanomedicine nanoscience novel novel diagnostics novel therapeutics prevent programs quadruplex DNA self assembly small molecule success symposium telomere three dimensional structure undergraduate student

项目摘要

At the subcellular level, humans like other organisms build and choreograph the countless structures essential to maintaining a healthy life by the process of self-assembly. Cells are in fact, enormously complex supramolecular entities that employ supramolecular nanoconstruction. Yet, improper self- assembly can also lead to diseases such as Alzheimer's, sickle-cell anaemia, etc. Therefore, mastering molecular self-assembly in aqueous media can lead to great advances in developing novel diagnostics and therapeutics. Supramolecular chemistry offers an attractive strategy for constructing self-made nanostructures by programming the appropriate information in their molecular building blocks. So far, supramolecular chemistry has made significant advances in constructing complex molecular machinery by self-assembly in organic media, but studies in aqueous media have lagged behind. There are still relatively few examples of discrete synthetic supramolecules based on small molecules held together solely with non-covalent interactions. There is a gap in the development of appropriate recognition motifs that are easy to make and offer robust and reliable self-recognition properties in aqueous environments. There is also a gap in the development of efficacious ligands that recognize G-quadruplex DNA (QDNA) with high specificity and affinity. We propose to fill these gaps by making small molecule guanine (G) derivatives (Aim 1) and studying their self-assembly in water (Aim 2). The usefulness of the resulting supramolecules will be highlighted by their use as self-assembled ligands (SALs) for the specific recognition of QDNA (Aim 3). QDNA is the subject of intense studies due to its putative role in telomere function and in the regulation of some oncogenes. The ensuing supramolecules should further our long-term goal of expanding nanomedicine's molecular 'toolbox' by developing better diagnostic probes and therapeutics.

在亚细胞水平上，人类和其他生物一样，通过自我组装的过程来构建和编排维持健康生命所必需的无数结构。事实上，细胞是极其复杂的超分子实体，它们采用超分子纳米结构。然而，不适当的自组装也可能导致诸如阿尔茨海默氏症、镰状细胞贫血等疾病。因此，掌握水介质中的分子自组装可以导致开发新的诊断和治疗的巨大进步。超分子化学提供了一个有吸引力的策略，通过在其分子构建块中编程适当的信息来构建自制的纳米结构。目前，超分子化学在有机介质中通过自组装构筑复杂分子结构方面取得了显著的进展，但在水介质中的研究相对滞后。仍然存在相对较少的基于仅通过非共价相互作用结合在一起的小分子的离散合成超分子的实例。在开发适当的识别基序方面存在差距，这些基序易于制造并在水性环境中提供稳健和可靠的自识别特性。在开发以高特异性和亲和力识别G-四链体DNA（QDNA）的有效配体方面也存在差距。我们建议通过制备小分子鸟嘌呤（G）衍生物（目标1）和研究它们在水中的自组装（目标2）来填补这些空白。所得到的超分子的有用性将通过它们作为用于QDNA的特异性识别的自组装配体（SAL）的用途而突出（Aim 3）。由于QDNA在端粒功能和某些癌基因的调控中的假定作用，QDNA是密集研究的主题。随后的超分子应该进一步扩大我们的长期目标，通过开发更好的诊断探针和治疗纳米医学的分子“工具箱”。