ZINC FINGER-INSPIRED FLUORESCENT CHEMOSENSORS

锌指激发的荧光化学传感器

• 批准号: 8167512
• 负责人: JAMES E FLETCHER
• 金额: $ 3.53万
• 依托单位: UNIVERSITY OF NEBRASKA MEDICAL CENTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-05-01 至 2011-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8167512
• 关键词: Affect; Affinity; Amino Acids; Anions; Area; Binding; Cations; Chelating Agents; Chemicals; Communication; Computer Retrieval of Information on Scientific Projects Database; Detection; Engineering; Fluorescence; Funding; Generations; Goals; Grant; Institution; Investigation; Ions; Knowledge; Lead; Measurement; Mission; Molecular; Nature; Nebraska; Output; Peptides; Point Mutation; Relative (related person); Research; Research Personnel; Resources; Role; Signal Transduction; Source; System; United States National Institutes of Health; Variant; Zinc; Zinc Fingers; base; design; insight; programs; sensor; small molecule; tool; toxic metal

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. Interactions between peptide residues and cations, such as that between Zn+2 and the zinc finger (ZnF) motifs, are vital constituents of cellular communication. The proposed investigation is relevant to the mission of Nebraska's INBRE program in that it will advance knowledge in the area of cell-signaling affected by interactions with zinc. Developing new sensor systems based on ZnF motifs will allow direct measurement of how zinc affinity varies with peptide identity and permit direct measurements to be made regarding the binding affinities of toxic metal ions relative to Zn+2 for a prescribed set of peptide chelating motifs. Such studies will lead to new insights as to how ZnF's exert selectivity for zinc and how toxic metals might lead to cellular damage. While using a synthetic chemical approach to better understand nature, this project will also exploit nature to develop new tools for ion and small molecule sensing, as the molecules developed for these studies will stand as new sensors for zinc detection. This study's first generation systems will be based on well-known ZnF chelator-analyte interactions (CCHH ZnF motif with Zn+2) in order to facilitate efficient structural optimization of the system's fluorescent output. Once optimized, point-mutation studies will be performed by modulating amino acid residue identities with the goal of discovering new derivatives selective for varying analytes. Uniquely, the proposed sensors have been designed to also allow the wavelength of arene fluorescence output to be modified independently of peptide variations, promising the ability to engineer multicolor readouts for varying analytes within a single chemosensor design. Because amino acid residues serve as the analyte recognition units in these systems, any analytes capable of noncovalently interacting with peptides could potentially be targeted using this general molecular approach (including cations, anions and small organic molecules). Hence, discoveries made in the proposed investigation will not only advance the understanding zinc's role in cellular communication but will also impact the field of fluorescence chemosensing.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 肽残基和阳离子之间的相互作用，例如 Zn+2 和锌指 (ZnF) 基序之间的相互作用，是细胞通讯的重要组成部分。 拟议的研究与内布拉斯加州 INBRE 计划的使命相关，因为它将推进受锌相互作用影响的细胞信号传导领域的知识。 开发基于 ZnF 基序的新传感器系统将允许直接测量锌亲和力如何随肽特性变化，并允许直接测量有毒金属离子相对于规定的一组肽螯合基序的 Zn+2 的结合亲和力。 此类研究将带来关于 ZnF 如何发挥对锌的选择性以及有毒金属如何导致细胞损伤的新见解。在使用合成化学方法更好地了解自然的同时，该项目还将利用自然来开发用于离子和小分子传感的新工具，因为为这些研究开发的分子将作为锌检测的新传感器。 本研究的第一代系统将基于众所周知的 ZnF 螯合剂-分析物相互作用（CCHH ZnF 基序与 Zn+2），以促进系统荧光输出的有效结构优化。 一旦优化，点突变研究将通过调节氨基酸残基特性来进行，目的是发现对不同分析物具有选择性的新衍生物。 独特的是，所提出的传感器的设计还允许独立于肽变化而修改芳烃荧光输出的波长，从而有望在单个化学传感器设计中为不同的分析物设计多色读数。 由于氨基酸残基在这些系统中充当分析物识别单元，因此任何能够与肽非共价相互作用的分析物都可以使用这种通用分子方法（包括阳离子、阴离子和小有机分子）作为目标。 因此，拟议研究中的发现不仅将增进对锌在细胞通讯中作用的理解，还将影响荧光化学传感领域。