Development of a Novel Lysophosphatidic Acid Activity Probe to Identify and Characterize New Protein Targets

Author

Leah M. Cuthriell, University of Tennessee - Knoxville

Date of Award

12-2009

Degree Type

Thesis

Degree Name

Master of Science

Major

Chemistry

Major Professor

Michael Best

Committee Members

David Baker, Frank Vogt

Abstract

Lipids are categorized according to their biological function. Phospholipids, glycolipids, and cholesterol are bulk membrane lipids that offer structure and support to the cells and organelle membranes. Signaling lipids include diacylglycerol, phosphatidic acid, and lysophosphatidic acid (LPA). These are low abundance lipids that are active in various pathways. LPA acts through GPCR receptors to activate G or beta mediated stimulation of phospholipase C leading to phosphatidylinositol-(4,5)-bisphosphate hydrolysis, G_i mediated inhibition of adenyl cyclase, and G_i mediated stimulation of the mitogenic Ras- MAP kinase. To further elucidate the biological activity of LPA and potentially identify new LPA binding receptors, activity based protein profiling (ABPP) can be utilized to label and identify enzymes. This thesis discusses the development of an LPA activity probe which incorporates a benzophenone group that can be photocrosslinked to a protein via ultraviolet radiation and a secondary azide tag to facilitate purification of the probe and bound protein.

Recommended Citation

Cuthriell, Leah M., "Development of a Novel Lysophosphatidic Acid Activity Probe to Identify and Characterize New Protein Targets. " Master's Thesis, University of Tennessee, 2009.
https://trace.tennessee.edu/utk_gradthes/520