Discipline: Chemistry & Chemical Sciences
Subcategory: STEM Research
Jacqueline Smith - Bowie State University
Co-Author(s): Brenda Tankeu and Marissa Savory, Bowie State University
There are many biological processes of which the scientific community is still working to fully understand. Due to their stability, reversibility and selectivity, small molecules can be used to understand how specific proteins play a role in cellular pathways. The cell has many adaptive mechanisms used for the cellular repair during endoplasmic reticulum (ER) stress. If proteostasis is not re-established, unfolded proteins are tagged for clearance through the ubiquitin-proteasome system (UPS). Aberrant cells have been shown to exploit these prosurvival mechanisms as a way to circumvent cell death. However proteasome disruption leads to cell death. Valosin-containing protein (VCP) is a key component of the UPS which can be targeted to investigate its role in proteostasis. Small molecule heterocycles such as imidazoles have the potential to allosterically bind to VCP to disrupt the UPS in rogue cells. We propose a two-step synthesis of a library of novel imidazole compounds through microwave-assisted multicomponent reactions. Using microwave energy, this method will allow a variety of imidazole compounds to be rapidly synthesized. Ultimately these compounds will be used to identify the structural features which are key for allosteric binding to VCP. Understanding how these small molecules affect proteins involved in cellular stress and repair can help scientists understand and control cell death.
Funder Acknowledgement(s): National Science Foundation Award #1800165
Faculty Advisor: None Listed,