Amino acids are the building blocks of life and are used in biology to prepare important materials of various types (i.e. proteins, peptides, hormones, etc). Small peptides have shown to be biologically active and can be used in a variety of situations. However, small peptides are frequently degraded by the presence of endogenous enzymes ultimately reducing their ability to achieve their biological function in an efficient manner. Unnatural amino acids, i.e. amino acids that are either not found or only rarely found in nature, have shown an ability to impart stability to small peptides towards enzymatic degradation. The Masterson Research Group (MRG) is particularly interested in two small peptides (Somatostatin and Neurotensin), which show a wide range of biological activity. The MRG has developed techniques that allow for the preparation of a variety of unnatural amino acids from a common synthetic intermediate. The synthetic strategy developed by the MRG allows for the parallel preparation of a variety of unnatural amino acids of importance to Somatostatin and Neurotensin. The unnatural amino acids will be used to replace specific amino acids in Somatostatin and Neurotensin. The peptide analogues will be tested for their ability to resist degradation by enzymes and for their ability to carry out their biological function. It is a key aim of this research to expand the scope of the techniques developed by the MRG to prepare a wide variety of novel unnatural amino acids and study their effect on peptide stability and function.
Broader Impacts of the Project: The methods developed in this research will have a broad impact to the scientific community by providing efficient methods of preparing unnatural amino acids. The peptides prepared in this project will also provide valuable information on the structure-function relationships for Somatostatin and Neurotensin. The methods and materials will find broad applicability in bioorganic and materials sciences. The project is an interdisciplinary project that merges the areas of enzymology, traditional organic synthesis, biological chemistry, and mass spectrometry into a single project relevant to the biological sciences and chemistry. The project will allow for the training of the next generation of scientists in the state of Mississippi and will provide significant educational opportunities for graduate research assistants, undergraduate students, and economically disadvantaged high school student participants. The project will use some of the developed methodology from the MRG to teach a class at the graduate level. The class is titled "Mass Spectrometry: Useful for more than m/z" and will train graduate students on the use of NSF-funded mass spectrometry facilities at USM. The course will utilize an assay developed in the MRG to determine enantioselectivity from an enzymatic hydrolysis reaction (a process that is central to the synthetic methodology described above). The students will learn how to use the facilities so that they can make use of them in their own research endeavors and the MRG will be able to use the course to obtain the much needed data from the assays that the students will perform during the course. Mass spectrometry has become a routine method of analyzing a variety of molecules and the students who successfully complete the course will have gained skills that are transferable to a variety of job opportunities. The acquired skills will make the students highly competitive in an ever changing global job market.
