Enhanced synthetic luciferin substrates for firefly luciferase

萤火虫荧光素酶的增强型合成荧光素底物

基本信息

批准号：
9457283
负责人：
STEPHEN C. MILLER
金额：
$ 35.48万
依托单位：
UNIV OF MASSACHUSETTS MED SCH WORCESTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-09-30 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9457283
关键词：
Adopted Affinity Amination Amines Animal Model Animals Biological Assay Bioluminescence Brain Brain Neoplasms Cells Central Nervous System Viral Diseases Chemistry Circadian Rhythms Complex Dependovirus Detection Disease Progression Electrons Enzymes Event Fireflies Firefly Luciferases Fluorescence Gene Expression Genetic Glioblastoma Growth Image Image Enhancement Inflammation Light Luciferases Methods Molecular Molecular Probes Monitor Mus Mutate Mutation Neuraxis Neurodegenerative Disorders Neurons Optical reporter Order Coleoptera Organism Oxides Performance Permeability Process Property Reporter Reporting Route Structure Tissues Transgenic Animals Virus Diseases Work analog animal imaging bioluminescence imaging cell growth cost drug candidate drug discovery hydroxyl group imaging modality improved in vivo in vivo bioluminescence imaging in vivo imaging interest internal control light emission lipophilicity luciferin mutant neoplastic cell novel strategies novel therapeutics portability real world application sensor treatment response

项目摘要

Bioluminescence assays and imaging methods have been widely adopted for drug discovery because of their simplicity, robustness, and low-cost. The inherently low background and lack of need for excitation light makes bioluminescence superior to fluorescence methods for many applications. Nevertheless, bioluminescence has yet to reach its full potential. We propose the following specific aims: 1) Expand the scope of bioluminescence imaging with synthetic luciferins; 2) Develop bright and functionally orthogonal luciferases suitable for in vivo imaging; and 3) Leverage “portable reporters” for imaging in any animal. We will exploit the properties of synthetic luciferin analogs to enhance the imaging of invasive brain tumors, viral infection of the CNS, and circadian rhythms. We will develop fully orthogonal luciferin-luciferase pairs that can serve as internal controls and enable multiplexed imaging. Finally, we will overcome the restricted set of available luciferase-expressing animals by developing bioluminescent reporters that can be introduced into any animal of interest.

生物发光测定和成像方法已被广泛采用药物发现因其简单性、稳健性和低成本而受到关注。背景和不需要激发光使得生物发光优于然而，生物发光技术尚未在许多应用中得到应用。我们提出以下具体目标： 1) 扩大范围。使用合成荧光素进行生物发光成像；2) 开发明亮且功能齐全的产品适用于体内成像的正交荧光素酶；3) 利用“便携式生产商” 我们将利用合成荧光素类似物的特性来对任何动物进行成像。增强侵袭性脑肿瘤、中枢神经系统病毒感染和昼夜节律的成像我们将开发完全正交的荧光素-荧光素酶对，可以用作最后，我们将克服限制。通过开发生物发光生产者获得一组可用的表达荧光素酶的动物可以将其引入任何感兴趣的动物中。