A Simple and Robust Indicator for Glutathione

简单而可靠的谷胱甘肽指标

基本信息

批准号：
8627059
负责人：
ROBERT M STRONGIN
金额：
$ 43.46万
依托单位：
PORTLAND STATE UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-04-01 至 2017-03-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8627059
关键词：
Accounting Amino Acids Autistic Disorder Basic Science Binding Biohazardous Substance Biological Biological Assay Biological Markers Blood Blood specimen Cardiac Surgery procedures Cause of Death Cells Cessation of life Chemicals Chronic Disease Chronic Kidney Failure Clinical Research Data Detection Diagnosis Diagnostic tests Disease Disease Progression Erythrocytes Evaluation Evaluation Studies Exhibits Fingers Fluorescence Fluorescence Resonance Energy Transfer Generations Glutathione Goals Health Heart failure Heel Hemoglobin Human Knowledge Label Laboratories Life Liver diseases Lung diseases Malignant Neoplasms Measurement Medicine Methodology Methods Mitochondrial Diseases Monitor Optics Parkinson Disease Pathogenesis Patients Peritoneal Dialysis Physiological Plasma Play Postoperative Period Process Property Protons Reporting Research Research Personnel Role Running Sampling Signal Transduction Testing Therapeutic Intervention Time Variant Whole Blood Work analytical method base cost design flexibility fluorophore innovation interest minimally invasive oxidation point of care public health relevance receptor response simulation validation studies

项目摘要

Chronic diseases are the leading cause of death in the world, accounting for over 60 % of all fatalities. Decreased levels of the tripeptide glutathione (GSH) are well-known to be associated with chronic diseases and are of interest in monitoring disease progression and therapeutic interventions. For example, recent studies show that monitoring whole blood glutathione (GSH) levels can be of benefit towards diagnosing asymptomatic heart failure and mitochondrial disorders. GSH monitoring is also useful in the health assessment of patients with chronic renal disease or post-operative open heart surgery. However, reported levels of GSH in both healthy subjects and patients exhibit inter-laboratory variation. Plasma GSH levels are often reported despite the fact that they account for less than 0.5 % of the circulating GSH. Divergent sample processing and conjugation steps propagate inter-laboratory variability, as they result in varying degrees of sample oxidation and labeling. In order to achieve consistent and efficient GSH monitoring, the major goal of this proposal is to develop a fluorescent indicator that functions directly in minimally-diluted whole blood. In order to achieve this goal, the following specific aims are proposed: 1. Design, synthesis and evaluation of NIR-active GSH-selective indicators. Based on the preliminary data referred to above, our working hypothesis is that highly selective indicators for GSH can be designed to bind GSH via multipoint supramolecular interactions and produce concomitant fluorescence signals without optical interference from hemoglobin or other blood components. 2. Develop methodology for detection and quantitation of GSH in whole blood. We postulate, again on the basis of our preliminary data, that selectivity and sensitivity for GSH over a disease-relevant range can be achieved in human blood via the design of GSH-selective NIR active probe-containing receptors. The studies proposed in this aim are thus focused on optimization and demonstration of the utility of the proposed design principles and synthetic indicators via extensive evaluation and validation studies.

慢性病是世界上最主要的死亡原因，占所有死亡人数的60%以上。众所周知，三肽谷胱甘肽 (GSH) 水平的降低与慢性疾病有关。疾病，并对监测疾病进展和治疗干预感兴趣。为了例如，最近的研究表明，监测全血谷胱甘肽 (GSH) 水平可能有益诊断无症状心力衰竭和线粒体疾病。 GSH 监测还可用于慢性肾病或心脏直视术后患者的健康评估外科手术。然而，健康受试者和患者的 GSH 水平报告显示实验室间差异变化。血浆 GSH 水平经常被报告，尽管事实上它们只占不到 0.5% 循环中的 GSH。不同的样品处理和缀合步骤在实验室间传播变异性，因为它们会导致不同程度的样品氧化和标记。为了达到一致和高效的 GSH 监测，该提案的主要目标是开发一种荧光直接在最低限度稀释的全血中起作用的指示剂。为了实现这一目标，提出以下具体目标： 1. NIR活性GSH选择性指标的设计、合成和评价。根据上述初步数据，我们的工作假设是高度选择性 GSH 指示剂可以设计为通过多点超分子相互作用结合 GSH，产生伴随的荧光信号，不受血红蛋白或其他物质的光学干扰血液成分。 2. 开发全血中 GSH 的检测和定量方法。我们再次根据我们的初步数据假设，GSH 的选择性和敏感性通过 GSH 选择性设计，可以在人体血液中实现超过疾病相关范围的检测含有 NIR 活性探针的受体。因此，本目标提出的研究重点是所提出的设计原理和合成的实用性的优化和论证通过广泛的评估和验证研究得出的指标。

项目成果

期刊论文数量（9）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（1）

Recent progress in chromogenic and fluorogenic chemosensors for hypochlorous acid.

DOI：
10.1039/c6an00158k
发表时间：
2016-03-21
期刊：
The Analyst
影响因子：
0
作者：
Yue Y;Huo F;Yin C;Escobedo JO;Strongin RM
通讯作者：
Strongin RM

Varied Length Stokes Shift BODIPY-Based Fluorophores for Multicolor Microscopy.

DOI：
10.1038/s41598-018-22892-8
发表时间：
2018-03-15
期刊：
Scientific reports
影响因子：
4.6
作者：
Bittel AM;Davis AM;Wang L;Nederlof MA;Escobedo JO;Strongin RM;Gibbs SL
通讯作者：
Gibbs SL

Assessment of human pancreas cancer tissue and precursor lesions via a fluorophore with inherent PDAC selectivity.

通过具有固有 PDAC 选择性的荧光团评估人类胰腺癌组织和癌前病变。

DOI：
10.1016/j.ymeth.2019.06.008
发表时间：
2019
期刊：
Methods (San Diego, Calif.)
影响因子：
0
作者：
Munhenzva,IanR;Barth,ConnorW;Sibrian-Vazquez,Martha;Wang,LeiG;Escobedo,JorgeO;Gibbs,SummerL;Strongin,RobertM
通讯作者：
Strongin,RobertM

Far-Red and Near-Infrared Seminaphthofluorophores for Targeted Pancreatic Cancer Imaging.

DOI：
10.1021/acsomega.6b00403
发表时间：
2017-01-31
期刊：
ACS omega
影响因子：
4.1
作者：
Wang L;Barth CW;Sibrian-Vazquez M;Escobedo JO;Lowry M;Muschler J;Li H;Gibbs SL;Strongin RM
通讯作者：
Strongin RM

A simple assay for glutathione in whole blood.