Peptides are amazing molecules. In the body peptides are used as chemical messengers to signal between cells as hormones (such as insulin) and neuropeptides (endorphins). Peptides are also used as toxins to defend us against bacteria, and in other species, to kill predators or prey. In addition to these roles for endogenous peptides, synthetic peptides have been used as research tools to alter protein-protein interactions that are essential for cellular functions. Because of their importance in biological processes, peptides have been the focus of research aimed at developing drugs for a wide range of conditions. The first step of drug discovery is target identification. Using a novel peptidomics technique, we have identified hundreds of peptides, including some that function as neuropeptides involved in food intake and body weight regulation. Other peptides found in the peptidomics screens are not likely to function as neuropeptides, but may instead play a role in regulating protein-protein interactions within cells, a novel role for endogenous peptides. A new class of anti-cancer drugs -- the proteasome inhibitors -- greatly alters the intracellular peptidome, raising the possibility that this contributes to the mechanism of action of these drugs. The focus on peptides will be related to the issue of drug discovery in general, and the need for retro-translational research—going deeper into basic science to understand mechanisms of drug action.
Professor of Molecular Pharmacology and Neuroscience, Albert Einstein College of MedicineNo slides available
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