Chemistry Department Seminar: Grace Yin Stokes, Santa Clara University
Thermodynamic Studies of Artificial Plasma Membranes Elucidate Drug Design Principles
Small molecule pharmaceutical drugs may adsorb to and perturb the physical structure of lipids in the mammalian plasma membrane. These non-specific interactions impact bioaccumulation and toxicity. They may also change the conformation and function of transmembrane proteins, such as G-protein coupled receptors (GPCRs). GPCRs are the target of over half of all FDA-approved drugs. The Stokes Lab uses a laser-based analytical method, second harmonic generation (SHG), to monitor adsorption of therapeutically-relevant concentrations of neurological drugs (clozapine, olanzapine and chlorpromazine) to lipid membranes that represent the blood-brain barrier. These studies quantified the molecular-level forces which drive adsorption. We are trying to provide a molecular-level understanding of how chemical structure alters membrane association. We have also conducted systematic studies of lipid adsorption with a small library of peptoids, N-substituted glycine oligomers, which are easy to synthesize and can serve as drug mimics.
*This seminar counts towards the chemistry major seminar attendance requirement.