With this award, the Macromolecular, Supramolecular, and Nanochemistry Program of the Division of Chemistry is funding Professor Timothy Glass of the University of Missouri-Columbia to design and synthesize molecular sensors for two specific classes of lipids. Lipids are a diverse group of molecules with a variety of biological functions. In addition to serving as the structural components of cell membranes and energy storage units in plants and animals, many lipids and lipid-containing compounds possess important biological activities and play significant roles in the development of various human diseases. Therefore, the ability to detect specific types of lipids provides a method to detect the diseases and in some cases treat them. Towards this long term goal, Prof. Glass conducts fundamental studies to gain a better understanding of the interactions between lipids and synthetic receptors. His research aims to provide guiding principles for designing organic molecules that recognize and bind specific types of lipids, signal their presence, and extract them from a membrane in which the lipid molecules are embedded in. This interdisciplinary project provides an excellent platform for research training of graduate and undergraduate students. In addition, Prof. Glass promotes science to the general public by developing content for a summer program to be held at the University of Missouri for high school teachers and students.
The first lipid targeted in these studies belongs to a class of oxidized phospholipid that has been shown to be important in the development of atherosclerosis. The second class of lipids, called glycolipids, are found on many cell surfaces and are involved in various processes such as cancer and inflammation. The molecular sensor is composed of a large hydrophobic cleft (for binding the hydrophobic tail of the target lipid and signal transduction) with some type of head-group binding functionality (for recognition of the head group of the target). For the oxidized phospholipid sensors, a hydrazine is used to bind to an aldehyde of the oxidized lipid providing selectivity for just this type of lipid. For the glycolipids, a boronic acid-based binding group is used to provide selectivity for sugar-containing lipids. The head-group binding moiety is anticipated to be a sufficient "hook" to allow the receptor to extract the target lipid from the membrane in which it is embedded. The hydrophobic cleft then wraps around the lipid tail. The binding of the lipid target to the molecular sensor is expected to result in change in fluorescence emission intensity, signaling the presence of the target.
