SGER: Self-Activating Amino Acids in Peptide Synthesis

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The overall objective of this small grant for exploratory research is to demonstrate that N-phosphorylated amino acids can be self-activated during peptide synthesis through the formation of a cyclic carboxylic-phosphoric mixed anhydride. The known regiochemical preference for aminolysis at the carboxylate of carboxylic-phosphoric mixed anhydride is a key element to this approach. No technology currently exists for the self-activation of N-protected amino acids in peptide synthesis and the pioneering work in this area has been largely theoretical and aimed at understanding the central role that N-phosphorylated amino acids may have had in the pre-biotic assembly of peptides and oligonucleotides. This project is grounded in the translation of these theoretical studies into a practical and unique methodology for stepwise chemical peptide synthesis through the use of N-phosphorylated amino acids but without the need for additional coupling reagents.With this award, the Organic and Macromolecular Chemistry Program is supporting the research of Professor Clifford Berkman of the Department of Chemistry at Washington State University. Professor Berkman's research efforts revolve around the preparative methods and the chemistry of phosphorus-containing peptidomimetic structures. This chemistry, as it relates to this project, is expected to lead to a green process for peptide synthesis in which a reaction sequence for self-activation, peptide bond formation, and dephosphorylation will require only mild pH cycling. Successful development of this methodology will have an impact on peptide synthesis in the pharmaceutical and biotechnology industries.