The objective of this project is to determine the relationship between the structure of small peptides and their ability to affect lysosomal activity. To this end, a close collaboration between organic chemistry and biological science offers great potential for increasing understanding of the role of lysosomes in cellular homeostasis. Researchers and students involved with the proposed project will benefit from work to adopt new scientific knowledge and skills at the interface between organic chemistry and biology as they pursue work in the dynamic field that is lysosomal regulatory properties.
The goals of this project are:
1. Synthesize new, non-peptidyl derivatives of diazoketones. Previous studies were able to demonstrate that diazoketones have regulatory properties with respect to lysosomal activity. Because these properties are believed to be a consequence of interactions between the diazo group and the biological tissue, this project will examine the effect of other functional groups alone. Derivatives of Z-Phe-Ala-diazomethylketone (PADK) will be prepared, by replacing the diazo group and leaving the rest of the molecular structure intact.
2. Analyze structure of the compounds.
Because of the importance of the structure in determining the biological activity of the organic molecules, the structure of different derivatives will be analyzed using modern spectrometry techniques, such as high field NMR and LC-Mass Spectroscopy.
3. Test the new derivatives for lysosomal activity.
Following synthesis, purification and characterization, the new compounds will be tested for metabolic stability in vitro including metabolite composition, distribution, deposition, and synaptic integrity.
4. Evaluation and dissemination of results.
The results of this research will be disseminated in peer reviewed publications and student research presentations at local and regional meetings.