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.

该副本是利用众多研究子项目之一 由NIH/NCRR资助的中心赠款提供的资源。子弹和 调查员（PI）可能已经从其他NIH来源获得了主要资金， 因此，可以在其他清晰的条目中表示。列出的机构是 对于中心，这不一定是调查员的机构。 肽残基与阳离子之间的相互作用，例如Zn+2与锌指（ZnF）基序之间的相互作用是细胞通信的重要组成部分。 拟议的调查与内布拉斯加州的Inbre计划的使命有关，因为它将提高在与锌相互作用影响的细胞信号领域的知识。 基于ZNF基序开发新的传感器系统将允许直接测量锌亲和力如何随肽的身份变化，并允许直接测量有毒金属离子相对于Zn+2的有毒金属离子的结合亲和力，以供一组规定的肽螯合基序。 这些研究将导致有关ZNF如何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理解自然的同时，该项目还将利用性质开发新的离子和小分子传感工具，因为这些研究为这些研究开发的分子将成为锌检测的新传感器。 该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基元与Zn+2），以促进系统荧光输出的有效结构优化。 一旦优化，将通过调节氨基酸残基身份进行点突变研究，以发现针对不同分析物选择新的衍生物。 独特的是，所提出的传感器也设计为允许独立于肽变化的芳烃荧光输出的波长，并有望在单个化学传感器设计中设计多色的多色读数能力。 由于氨基酸残基充当这些系统中的分析物识别单元，因此使用这种通用分子方法（包括阳离子，阴离子和小有机分子），可以潜在地靶向与肽非共价相互作用的任何分析物。 因此，在拟议的研究中发现的发现不仅会推动理解锌在细胞通信中的作用，而且还会影响荧光化学传感的领域。