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Binuclear Complexes with Excited-State Proton Transfer for Pyrophosphate Sensor

用于焦磷酸盐传感器的具有激发态质子转移的双核配合物

基本信息

批准号：
8366228
负责人：
Yi Pang
金额：
$ 44.55万
依托单位：
UNIVERSITY OF AKRON
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：
2012-08-01 至 2017-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8366228
关键词：
ATP Hydrolysis Alzheimer&apos s Disease Amines Anions Attention Benzoxazoles Binding Biochemical Reaction Biological Biological Assay Biological Process Biology Bioluminescence Cell physiology Characteristics Chemicals Clinical Color Complex DNA DNA Sequence Detection Development Diphosphates Disease Dyes Elements Evaluation Event Fireflies Fluorescence Fluorescent Probes Genome Heart Diseases Hospitals Human Genome Indium Investigation Lead Medicine Metals Methods Modification Molecular Optics Oxygen Patients Phosphorus Play Price Process Protons RNA Research Role Scheme Signal Transduction Signaling Molecule Solutions Structure System Work analog base bone cell cost design genetic profiling human tissue improved inorganic phosphate metal complex nucleoside triphosphate optical switch polymerization prevent response sensor success tripolyphosphate

项目摘要

DESCRIPTION (provided by applicant): Pyrophosphate anion (PPi) is involved in many biological processes that include ATP hydrolysis, DNA and RNA polymerizations, and enzymatic reactions. The anion is now emerging as a specific signaling molecule in bones and cells. The level of PPi in human tissue is directly related to various enzymatic activities, whose abnormal activities can cause diseases such as heart disease and Alzheimer disease. The detection of pyrophosphate is also an essential component in the commercial DNA pyrosequencing, which provides the necessary genetic profile for hospital patients. Although the genome-based medicine can dramatically increase the efficiencies in the patient treatment, the current high cost associated with the DNA sequencing prevents its routine applications. The development of low cost method for PPi detection, therefore, has a profound impact on the disease studies and DNA sequencing. The current method to detect PPi is based on a complicated enzymatic process, involving two enzymatic reactions occurring in sequence. A simple fluorescent detection of PPi could greatly reduce the cost for this step, which ultimately leads to price reduction for DNA sequencing. The proposed research is dedicated to find a simple solution for non-enzymatic detection of PPi. Our approach is to synthesize a chemical sensor that integrates a binuclear Zn(II)-Zn(II) core into 2-(2'- hydroxyphenyl)benzoxazole structure. The PPi binding to the sensor will trigger the excited state intramolecular proton transfer (ESIPT), thereby leading to a large optical response. Preliminary results show that the new pyrophosphate sensors can provide a fluorescence-based bioassay that greatly simplifies the current pyrophosphate detection scheme. The developed sensor has the potential to be used in DNA pyrosequencing. PUBLIC HEALTH RELEVANCE: Detection of pyrophosphate anion is an important element in DNA pyrosequencing, which currently uses the complicated enzymatic reactions and provides essential information for genome-based medicine. The proposed research focuses on the development of highly selective pyrophosphate sensor, which can greatly simplify the costly enzymatic detection scheme for DNA pyrosequencing and therefore reduce the DNA sequencing cost. Success in the proposed direction will have an important impact in achieving economically acceptable human genome analysis in a clinical setting.

描述（由申请人提供）：焦磷酸阴离子（PPi）参与许多生物过程，包括ATP水解，DNA和RNA聚合以及酶促反应。阴离子现在作为一种特定的信号分子出现在骨骼和细胞中。人体组织中PPi水平与各种酶活性直接相关，酶活性异常可引起心脏病、阿尔茨海默病等疾病。焦磷酸盐的检测也是商业DNA焦磷酸测序的重要组成部分，它为医院患者提供了必要的遗传图谱。虽然基因组医学可以显著提高患者的治疗效率，但目前与DNA测序相关的高成本阻碍了其常规应用。因此，开发低成本的PPi检测方法对疾病研究和DNA测序具有深远的影响。目前检测PPi的方法是基于一个复杂的酶促过程，涉及两个酶促反应依次发生。简单的荧光检测PPi可以大大降低这一步的成本，最终导致DNA测序的价格降低。提出的研究致力于寻找一种简单的非酶检测PPi的解决方案。我们的方法是合成一种将双核Zn(II)-Zn（II）核心集成到2-（2'-羟基苯基）苯并恶唑结构中的化学传感器。与传感器结合的PPi将触发激发态分子内质子转移（ESIPT），从而导致较大的光学响应。初步结果表明，新的焦磷酸盐传感器可以提供基于荧光的生物测定，大大简化了目前的焦磷酸盐检测方案。该传感器具有应用于DNA焦磷酸测序的潜力。