Protein–membrane binding interactions denote crucial molecular recognition events that control key biological processes and are aberrant in many diseases including cancer. The characterization of these events is vital for understanding these processes and how they are transformed in disease. Signaling lipids are present at low percentages in cellular membranes. Their common role is to act as ligands in the binding and anchoring of proteins onto the membrane, which regulates both protein function and localization. Examples are diacylglycerol (DAG), phosphatidic acid (PA), and the family of seven naturally occurring phosphatidylinositol polyphosphates (PIP<sub>n</sub>s).  Synthetic lipid probes are invaluable for studying the biological roles of lipids. Our strategy for synthesizing lipid probes employs modular scaffolds that can be conveniently derivatized late in the synthesis. This allows for efficient production of many probes bearing different reporter tags that are useful for diverse applications. We have exploited this strategy to develop probes corresponding to DAG, PA, generic and the PIP<sub>n</sub>s. The resulting probes were shown to retain the biological activities of the natural lipids. We have investigated this protein-membrane binding by incorporating our probes on liposomal membranes. Our study is aimed at identifying and characterizing novel protein targets from cell extracts, and particularly those that are involved in disease onset.

Design and application of lipid probes for proteomic characterization of protein binding partners

249th National Meeting (2015)

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