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.

慢性疾病是世界上死亡的主要原因，占所有死亡人数的60％以上。三肽谷胱甘肽（GSH）的降低众所周知与慢性有关疾病，并在监测疾病进展和治疗干预措施方面很感兴趣。为了例如，最近的研究表明，监测全血谷胱甘肽（GSH）水平可能有益致力于诊断无症状的心力衰竭和线粒体疾病。 GSH监控也是可用于慢性肾脏疾病或术后心脏心脏的患者的健康评估外科手术。然而，报告的健康受试者和患者的GSH水平均表现出实验室间变化。血浆GSH水平通常报告为占0.5％的事实循环的GSH。不同的样本处理和共轭步骤传播实验室间变异性，因为它们导致样品氧化和标记的不同程度。为了实现该提案的主要目标是一致，高效的GSH监测，是开发荧光指示直接在最小降低的全血中起作用。为了实现这一目标，提出了以下特定目标： 1。设计，合成和评估NIR活性GSH选择指标。基于上面提到的初步数据，我们的工作假设是高度选择性 GSH的指标可以设计用于通过多点超分子相互作用和产生伴随的荧光信号，而没有血红蛋白或其他的光学干扰血液成分。 2。开发用于全血中GSH检测和定量的方法。我们再次根据我们的初步数据假设，对GSH的选择性和敏感性在与疾病相关的范围内可以通过设计GSH选择性实现 NIR主动探测受体。因此，此目标中提出的研究集中在提出的设计原理和合成的实用性的优化和演示通过广泛的评估和验证研究指标。

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

A simple assay for glutathione in whole blood.

DOI：
10.1039/c5an00345h
发表时间：
2015-05-21
期刊：
The Analyst
影响因子：
0
作者：
Hakuna L;Doughan B;Escobedo JO;Strongin RM
通讯作者：
Strongin RM

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