Development of non-covalent chemical probes for mu, delta and kappa opioid receptors

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Despite the fact that codeine has been isolated over 150 years ago little is known about its interaction with opioid receptors. The aim of the project is to deepen a fundamental understanding of the ligand-opioid receptor interaction. Our efforts will focus on the systematic synthesis of codeine dimers as non-covalent chemical probes for opioid receptors. Analysis of novel non-covalently bound dimers to the opioid receptor will lead to a better understanding of ligand-receptor interaction and new structure-function relationships will emerge from this study. The generation of new scientific knowledge will enhance our understanding of the structural requirements that govern this ligand-receptor function, and this new knowledge may shed light in comprehending other novel ligand-receptor pairs. The results of this project may eventually lead to the development of a new class of safe drugs by Purdue Pharma. Therefore, Canadians will benefit immensely from the availability of safe non-addictive painkillers. In addition to pain management, opioid receptors are widely involved in various physiological and pathophysiological activities, including the regulation of cell proliferation, emotional response, epileptic seizures, immune function, feeding, obesity, respiratory and cardiovascular control as well as some neurodegenerative disorders including Alzheimer's and Parkinson's diseases. Therefore, this study will have a broad impact from pharmacological point of view.