DEVELOPMENT OF PEPTIDE DRUGS
Dr. Szeto's laboratory is involved in the development of peptide drugs that target specific cellular targets. One project focuses on the development of agonists and antagonists that target specific subtypes of cell-surface receptors, with special emphasis on opioid, vasopressin and oxytocin receptors. These receptors play important roles in the regulation of pain processing, blood pressure, adrenocorticotropin release, and uterine contraction, respectively. By targeting specific subtypes of these receptors, it is possible to minimize side effects associated with the currently available receptor agonists and antagonists. Our laboratory has developed some of the most selective ligands for the mu opioid receptor and for the vasopressin V1b receptors. The second project focuses on the development of cell-permeable antioxidants. Oxidative free radicals are believed to be the underlying cause in aging. Free radicals are produced by the mitochondrial electron transport chain, and they can lead to cell death by oxidation of lipids, proteins, DNA and RNA. Mitochondria are central to the life of the cell, but it is also most vulnerable to free radical damage. Oxidative free radicals can lead to mitochondrial permeability transition and swelling, release of cytochrome c and activation of the caspase cascade resulting in apoptosis. Mitochondrial dysfunction is implicated in aging, ischemia-reperfusion damage, neurodegenerative diseases, atherosclerosis, inflammatory processes, and aging. We have designed small cell-permeable peptide drugs that are potent antioxidants. Furthermore, some of these peptides target mitochondria and protect against mitochondrial permeability transition, mitochondrial swelling and apoptosis. These are now being investigated for therapeutic potential against myocardial ischemia and stroke, neurodegenerative diseases such as Parkinson's disease and Huntington's disease. and hepatitis C viral infection.
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