New Approaches to Peptide Synthesis

纽约大学的Paramjit Arora获得了化学系生命过程化学项目的奖励，以开发更环保、更有效的肽合成方法。目前的肽合成利用固相方法，其中肽链的氨基酸连接按指定的顺序一次添加一个。这项技术在引入时彻底改变了肽合成，但目前实施的是一个高度浪费的过程，在典型的反应条件下，每个合成的酰胺键使用的多余试剂量是其5倍。阿罗拉教授的工作是建立在经典和肽合成的最新进展，以开发新的，更有效的方法。在新的方法中，多余的试剂被优化的催化剂取代，从而实现高效的“绿色”催化循环。这项研究在制药和生物医学工业中有应用。该项目为学生在化学和生物学的交叉领域提供了宝贵的训练。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。阿罗拉教授是美国国家科学基金会本科生化学生物学研究经验网站的共同负责人。该网站通过将项目研究纳入REU课程，向年轻科学家介绍这一快速发展且技术重要的研究领域。与诺伊曼大学化学系的艾米·布朗教授合作，建立了该大学有史以来第一个本科生研究课程，包括学生顶点研究项目。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既原子高效又可持续的酰胺键合成新方法。迫切需要一种不需要过量试剂的方法，这种方法足够温和，不会导致相邻立体中心的外旋化。在这个项目中，通过有机催化剂，在两个片段的羧基端和胺端之间短暂地加强氢键介导的分子内反应，加速了酰胺键的形成。新方法通过非共价和共价相互作用与底物接合，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，包括将基于项目科学的新实验室实验模块整合到纽约大学本科化学课程中。阿罗拉教授开发了教学模块，供13所传统黑人学院和波多黎各的12所学院的教师使用，并通过纽约大学教师资源网络传播。诺伊曼大学（Neumann University）是一所小型文理大学，为通勤学生提供服务，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。阿罗拉教授和布朗教授正在开发一门化学生物学课程，该课程不需要大量的资源，而是通过前沿的研究项目丰富课程，为学生提供扩展最新化学技术知识的机会。该奖项反映了美国国家科学基金会的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.