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.
