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New Approaches to Peptide Synthesis

肽合成的新方法

基本信息

批准号：
1807670
负责人：
Paramjit Arora
金额：
$ 60.68万
依托单位：
New York University
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-08-01 至 2022-07-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1807670&HistoricalAwards=false
关键词：
New Approaches Peptide Synthesis

项目摘要

Paramjit Arora of New York University is supported by an award from the Chemistry of Life Processes Program in the Division of Chemistry to develop more environmentally friendly and more efficient methods for the synthesis of peptides. Current peptide synthesis utilizes a solid phase approach, where the amino acid links of a peptide chain are added one at a time, in a specified sequence. This technique revolutionized peptide synthesis when it was introduced, but as currently implemented it is a highly wasteful process, with typical reaction conditions utilizing five times the amount of excess reagents for every amide bond synthesized. Professor Arora's work is building on classical and recent advances in peptide synthesis to develop new, more efficient approaches. In the new approach, excess reagents are replaced with optimized catalysts giving an efficient, "green" catalytic cycle. This research has applications in pharmaceutical and biomedical industries. The project provides valuable training to students at the interface of chemistry and biology. Students engaged in the project gain experience in molecular design, conformational analysis, organic synthesis, and biochemistry. Professor Arora co-directs the NSF Research Experiences for Undergraduates Site in Chemical Biology at NYU. This site introduces young scientists to this rapidly growing and technologically-important research field by incorporating studies from the project into the REU curriculum. A collaboration with Professor Amy Brown of the Neumann University Department of Chemistry is establishing the first-ever undergraduate research course at that university, including student capstone research projects. This project advances the fundamental understanding of human health and produces a well-educated, diverse workforce in STEM. The objective of this research is to develop new methods of amide bond synthesis that are both atom-efficient and sustainable. There is an urgent need for methods that do not require excess reagents and are mild enough to not lead to epimerizaton of adjacent stereocenters. In this project, amide bond formation is accelerated by organocatalysts that transiently enforce a hydrogen-bonding-mediated intramolecular reaction between the carboxyl and amine termini of two fragments. The new approach engages the substrates through non-covalent and covalent interactions to reduce the entropic penalty of organizing the optimal transition state for catalysis. The project includes significant educational and outreach activities including the integration of new laboratory experiment modules based on the science of the project within undergraduate chemistry courses at NYU. Professor Arora develops teaching modules for use by faculty at 13 Historically Black colleges and universities and 12 colleges in Puerto Rico---disseminated through the NYU Faculty Resource Network. Professor Amy Brown of Neumann University, a small liberal arts university that serves a commuter-student population including many students from groups traditionally underrepresented in STEM collaborates on this proposal. Professors Arora and Brown are developing a chemical biology course that does not require extensive resources but enriches the curriculum with cutting-edge research-based projects, providing opportunities for students to expand their knowledge of state-of-the-art chemistry techniques.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

纽约大学的Paramjit Arora得到了化学系生命过程化学项目的一个奖项的支持，以开发更环保、更有效的合成肽的方法。目前的肽合成利用固相方法，其中肽链的氨基酸连接以指定的顺序一次一个地添加。这种技术在引入时彻底改变了肽合成，但目前实施的是一种高度浪费的过程，典型的反应条件是对于每个合成的酰胺键使用五倍量的过量试剂。 Arora教授的工作是建立在肽合成的经典和最新进展的基础上，以开发新的，更有效的方法。在新的方法中，过量的试剂被优化的催化剂取代，从而产生高效的"绿色"催化循环。这项研究在制药和生物医学工业中有应用。该项目提供了宝贵的培训，学生在化学和生物学的接口。参与该项目的学生将获得分子设计、构象分析、有机合成和生物化学方面的经验。 Arora教授共同指导纽约大学化学生物学本科生NSF研究经验网站。该网站通过将该项目的研究纳入REU课程，向年轻科学家介绍了这个快速发展和技术重要的研究领域。与诺依曼大学化学系的艾米·布朗教授合作，正在建立该大学有史以来第一个本科研究课程，包括学生的顶点研究项目。该项目推进了对人类健康的基本理解，并在STEM领域培养了一支受过良好教育的多元化劳动力队伍。本研究的目的是开发新的方法，酰胺键的合成，都是原子效率和可持续发展。迫切需要不需要过量试剂并且足够温和以不导致相邻立构中心的差向异构化的方法。在这个项目中，酰胺键的形成是加速的有机催化剂，瞬时强制执行的羧基和两个片段的胺末端之间的氢键介导的分子内反应。新方法通过非共价和共价相互作用与底物结合，以减少组织催化的最佳过渡态的熵罚。该项目包括重要的教育和推广活动，包括在纽约大学本科化学课程中整合基于该项目科学的新实验室实验模块。阿罗拉教授开发了教学模块，供波多黎各13所历史上的黑人学院和大学以及12所学院的教师使用-通过纽约大学教师资源网络传播。诺依曼大学的艾米·布朗教授（Amy Brown）是一所小型文科大学，为通勤学生群体提供服务，其中包括许多来自传统上在STEM中代表性不足的群体的学生。 Arora和Brown教授正在开发一门化学生物学课程，该课程不需要大量资源，但通过前沿的研究项目丰富了课程，为学生提供了扩展最先进化学技术知识的机会。该奖项反映了NSF的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。