Unnatural amino acids have been successfully incorporated into peptides resulting in increased proteolytic stability as well as increased conformational stability. The principal investigator of this project has developed a novel strategy for the preparation of a wide variety of unnatural amino acids from a common synthetic intermediate derived from an enzymatic hydrolysis of a prochiral intermediate. This strategy allows for the ready preparation of a series of unnatural amino acids using straightforward synthetic strategies. This research will pursue the following goals: a) the parallel preparation of various homochirally similar amino acids from a common intermediate, b) the incorporation of select unnatural amino acids into short peptides of biological significance, and c) study the stability of the peptides incorporating select unnatural residues. It is a key aim of this research to develop straightforward strategies that allow for the rapid evaluation of the effect of unnatural amino acid residues on peptide stability. This research program will allow for the gathering of data which can be used in the future to develop peptides with increased stability. These peptide compounds may find significant use in sensors, and other materials of current importance. The synthetic methods developed in this research will have a broad impact to the scientific community in that it will allow for the preparation of a wide range of unnatural amino acids using a minimal number of synthetic manipulations. This methodology will find use not only in the area of bioorganic and biological chemistry. This project is an interdisciplinary project that merges the areas of enzymology, traditional organic synthesis, and biological chemistry into a single project relevant to the biological sciences.
Broader Impacts: The project involves training, educational and outreach activities. The information derived from this research will be incorporated into a "guest lecturer" program that will incorporate the topic of enzymes as catalysts for organic synthesis in the undergraduate curriculum at a number of universities. The data obtained from this project will be incorporated into the "guest lecturer" program and will be used as a method of disseminating the information to a more general audience. This project will allow for graduate and undergraduate students to broaden their research experiences which will make them competitive in the biotechnology job market following graduation. This project will have an impact on underrepresented minority groups within the state of Mississippi as The University of Southern Mississippi serves a relatively large minority student population.
