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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，因为它们的简单性，鲁棒性和低成本。固有的低背景技术和不需要激发光使得生物发光上级荧光方法用于许多应用。然而，生物发光还没有充分发挥其潜力。我们提出以下具体目标：（1）扩大生物发光成像与合成的荧光素; 2）开发明亮和功能适用于体内成像的正交引物;和3）利用“便携式报告物” 用于任何动物的成像。我们将利用合成的类胡萝卜素的特性，增强侵袭性脑肿瘤、CNS病毒感染和昼夜节律的成像节奏我们将开发完全正交的荧光素酶对，内部控制，并使多路复用成像。最后，我们将克服限制通过开发生物发光报道基因获得的一组表达转肽酶的动物可以被引入任何感兴趣的动物体内。