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Chemical design of amyloid targeting fluorescent probes

淀粉样蛋白靶向荧光探针的化学设计

基本信息

批准号：
10019794
负责人：
EMMANUEL A THEODORAKIS
金额：
$ 9.92万
依托单位：
UNIVERSITY OF CALIFORNIA, SAN DIEGO
依托单位国家：
美国
项目类别：
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-15 至 2023-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10019794
关键词：
Affect Affinity Alzheimer&apos s Disease Amino Acid Sequence Amyloid Amyloid Proteins Amyloid deposition Amyloidosis Antineutrophil Cytoplasmic Antibodies Binding Biological Biological Assay Biological Markers Biophysics Brain Cells Characteristics Chemicals Chemistry Clinical Clinical Trials Color Computer Models Creutzfeldt-Jakob Syndrome Dementia Deposition Detection Development Diagnosis Diagnosis Clinical Trials Discrimination Disease Disease Progression Eye Family Fingerprint Fluorescence Fluorescent Probes Human In Vitro Label Length Life Medicine Methods Molecular Monitor Morphology Nerve Degeneration Neuroblastoma Neurodegenerative Disorders Neurons Noise Optical Methods Optics Parkinson Disease Pathogenesis Pharmacology Phase Prion Diseases Property Proteins Publications Research Retinoblastoma Savings Senile Plaques Sensitivity and Specificity Signal Transduction Solubility Structure Study models Symptoms Testing Theoretical model Therapeutic Intervention Time Tissues Toxic effect Translating Visualization Work accurate diagnosis age related amyloid imaging aqueous base biomaterial compatibility biophysical analysis biophysical properties clinical Diagnosis clinical application cytotoxicity density design diagnostic accuracy disease diagnosis drug candidate effective therapy electronic structure human tissue improved indexing novel diagnostics novel strategies prevent protein aggregation small molecule stem tool tool development

项目摘要

Chemical design of amyloid targeting fluorescent probes Project Summary Deposition of amyloid plaques in the brain represents a universal feature of many neurodegenerative diseases and precedes their clinical symptoms by several years. Thus, the specific detection of amyloid plaques can be used as a biomarker for the diagnosis of neurodegeneration, allowing the opportunity for disease-modifying therapeutic intervention. We have recently designed a new family of fluorescent probes that can label amyloids in tissue. Importantly, our results demonstrate, for the first time, that these probes enhance visualization of amyloids and also make it possible to colorimetrically differentiate the amyloids as a function of their protein composition. This unique ability may enable accurate diagnosis/monitoring of specific neurodegenerative diseases, thereby aiding in selection of a proper course of treatment. Here, we propose to evaluate the structural and electronic parameters that allow the rational design of fluorescent probes for amyloid discrimination. This work will result in new information of fundamental significance to the inherent properties of amyloids and immediate applicability to the development of new diagnostics. The specific aims of this proposal are to: a) develop and experimentally test a theoretical model for the rational design of amyloid targeting fluorescent probes (ATFPs); b) use rationally designed ATFPs to characterize amyloids based on their relative permittivity values and develop an ATFP-based fingerprinting assay; c) develop ATFPs with enhanced optical/biological properties by modifying their chemical/electronic structure; and d) evaluate the biophysical properties of ATFPs in solution and in tissue.

淀粉样蛋白靶向荧光探针的化学设计项目摘要大脑中淀粉样斑块的沉积是许多神经退行性疾病的普遍特征。比他们的临床症状早几年。因此，对淀粉样斑块的特异性检测可以被用作诊断神经退行性变的生物标记物，使疾病有机会得到改善治疗性干预。我们最近设计了一系列新的荧光探针，可以标记组织中的淀粉样蛋白。重要的是，我们的结果第一次表明，这些探针增强了淀粉样蛋白的可视化，也使得能够以颜色计量学区分淀粉样蛋白作为以下函数它们的蛋白质组成。这种独特的能力可以实现对特定目标的准确诊断/监控神经退行性疾病，从而帮助选择适当的疗程。在此，我们建议评估允许合理设计荧光探针的结构和电子参数淀粉样蛋白歧视。这项工作将产生对固有的具有根本意义的新信息淀粉样蛋白的特性和对新诊断开发的即刻适用性。的具体目标这项建议是：a)发展和实验检验合理设计淀粉样蛋白的理论模型。靶向荧光探针(ATFP)；b)使用合理设计的ATFP来表征淀粉样蛋白它们的相对介电系数值，并开发基于ATFP的指纹分析；c)开发ATFP 通过改变其化学/电子结构来增强光学/生物性能；以及d)评估 ATFP在溶液和组织中的生物物理性质。

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Electrochemical potential enables dormant spores to integrate environmental signals.

电化学潜力使休眠的孢子能够整合环境信号。

DOI：
10.1126/science.abl7484
发表时间：
2022-10-07
期刊：
Science (New York, N.Y.)
影响因子：
0
作者：
通讯作者：

Method to discriminate amyloids using fluorescent probes.

使用荧光探针区分淀粉样蛋白的方法。

DOI：
10.1016/bs.mie.2020.04.010
发表时间：
2020
期刊：
Methods in enzymology
影响因子：
0
作者：
Teppang,KristineL;Ehrlich,RachelS;Yang,Jerry
通讯作者：
Yang,Jerry

Site-Specific C-Terminal Fluorescent Labeling of Tau Protein.

DOI：
10.1021/acsomega.2c06139
发表时间：
2022-12-20
期刊：
ACS OMEGA
影响因子：
4.1
作者：
Bryan, Louise;Awasthi, Saurabh;Li, Yuanjie;Nirmalraj, Peter Niraj;Balog, Sandor;Yang, Jerry;Mayer, Michael
通讯作者：
Mayer, Michael

Fluorescent molecular rotors as versatile in situ sensors for protein quantitation.

DOI：
10.1038/s41598-023-46571-5
发表时间：
2023-11-22
期刊：
Scientific reports
影响因子：
4.6
作者：
通讯作者：

Exploring the Effect of Aliphatic Substituents on Aryl Cyano Amides on Enhancement of Fluorescence upon Binding to Amyloid-β Aggregates.

DOI：
10.1021/acschemneuro.1c00334
发表时间：
2021-08-04
期刊：
ACS CHEMICAL NEUROSCIENCE
影响因子：
5
作者：
Ehrlich, Rachel S.;Shiao, Alexander L.;Li, Meihan;Teppang, Kristine L.;Jeoung, Kun Yong;Theodorakis, Emmanuel A.;Yang, Jerry
通讯作者：
Yang, Jerry