Development of versatile lipid analogs for investigating protein-lipid binding interactions

ORGN 584

Matthew Smith, Denghuang Gong, and Michael Best, mdbest@utk.edu. Department of Chemistry, University of Tennessee at Knoxville, Knoxville, TN 37996
Binding events in which proteins interact with lipids in the cell membrane are crucial as they have been implicated in numerous normal and disease-related cellular processes. It is by this mechanism that signaling lipids such as diacylglycerol and phosphatidic acid often act as important regulators of protein function and localization. A beneficial approach to understanding these pathways involves the development of synthetic analogs that mimic the natural species but are modified to allow for characterization of binding at the molecular level. The described research focuses on the development of novel lipid-based probes that possess a reactive tag within the structure. These versatile compounds can be directly modified to generate a wide range of derivatives such as fluorescent- and photoaffinity-tagged analogs and tethered multivalent compounds. The design and synthesis of these probes will be presented along with progress in biological studies aimed at advancing the understanding of protein-membrane binding.