| 项目编号: | 1553860
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| 项目名称: | CAREER: Molecular Engineering of Bio-orthogonal Stabilized Alpha Helices |
| 作者: | Greg Thurber
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| 承担单位: | University of Michigan Ann Arbor
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| 批准年: | 2016
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| 开始日期: | 2016-03-01
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| 结束日期: | 2021-02-28
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| 资助金额: | 500000
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| 资助来源: | US-NSF
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| 项目类别: | Standard Grant
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| 国家: | US
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| 语种: | 英语
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| 特色学科分类: | Engineering - Chemical, Bioengineering, Environmental, and Transport Systems
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| 英文关键词: | engineering
; helix
; proposal
; diverse engineering student
; student
; biomedical engineering field
; career award
; molecular engineering research
; alpha helix
; career proposal
; biochemical engineering program
; novel helix
; greg novel molecular engineering strategy
|
| 英文摘要: | 1553860
Thurber, Greg
Novel molecular engineering strategies are rapidly enabling the development of unique bio-inspired molecules for materials, separations, drug, and medical imaging agent applications. However, these natural molecules often degrade at the conditions necessary for their use, such as in acidic or basic pH solutions when purifying a product or in the body where enzymes degrade the compounds before they can reach their therapeutic target. By using synthetic organic molecules to stabilize these biological materials, the agents can be engineered with both vast complexity and high stability. Furthermore, by choosing an appropriate chemical technique, high-throughput methods can be developed to rapidly select useful molecules from libraries of millions of compounds. This work will support basic research into the fundamental properties of these semi-synthetic materials and enable applied research to develop novel compounds for diverse applications.
This CAREER proposal will combine novel synthetic linkers, non-natural amino acid (NNAA) incorporation, and bio-orthogonal chemistry with directed evolution to engineer stabilized helices with unique targeting properties. Aim 1 of this proposal will characterize a novel series of azide-alkyne stabilized alpha helices that possess unique chemical, imaging, and pharmacokinetic properties and are compatible with cell surface directed evolution. This arrangement only requires one type of NNAA in the peptide backbone to reduce complexity and increase overall incorporation efficiency. The longer linker can be engineered with a functional handle for attachment to beads, fluorescent dyes, radiolabels, or pharmacokinetic modifiers. This modular design enables these molecules to be used in multiple applications including separations, intracellular targeting, and imaging. Aim 2 of the proposal will capitalize on the bio-orthogonal chemistry to select novel helices. A site-specific linkage is introduced to select for molecules that will retain binding while attached to the linker. This proposal will alleviate the current development bottleneck by screening millions of novel stabilized helices for new therapeutics, imaging agents, and separations components. Engineering functionally diverse stabilized peptide and protein structures will impact several fields including the chemical industry, biomedical engineering field, pharmaceutical industry, and medical community.
To grow the pipeline of highly qualified and diverse engineering students to fulfill these jobs, a science-focused outreach program will be created for students from local under-resourced schools in the Detroit area. Multiple interactions with students from predominantly under-represented backgrounds facilitate hands-on activities directly related to molecular engineering research. These students will visit the University of Michigan for interactive sessions to enhance their scientific understanding and encourage them to pursue science, technology, engineering, and mathematics (STEM) fields.
This CAREER award by the Biotechnology and Biochemical Engineering Program of the CBET Division is co-funded by the Systems and Synthetic Biology Program of the Division of Molecular and Cellular Biosciences. |
| 资源类型: | 项目
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| 标识符: | http://119.78.100.158/handle/2HF3EXSE/92756
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| Appears in Collections: | 全球变化的国际研究计划
科学计划与规划
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| Recommended Citation: | |
Greg Thurber. CAREER: Molecular Engineering of Bio-orthogonal Stabilized Alpha Helices. 2016-01-01.
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