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PortoghesePS

Research Abstracts Online
January - December 2011

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University of Minnesota Twin Cities
College of Pharmacy
Department of Medicinal Chemistry

PI: Philip S. Portoghese

Visualization of Opioid Receptor Heteromers

This group’s work focuses on the synthesis and pharmacology of ligands that target opioid receptors. Opioid receptors belong to the seven-transmembrane G-protein coupled receptor (GPCR) superfamily of membrane receptors. Classical pharmacological theory suggests that receptor agonists bind to a single receptor and initiate a signaling cascade dependant upon activation of the single receptor unit to produce their observable effects. Increasing evidence over the past decade has called the single receptor signaling unit into question as an overly simplistic representation of the actions of ligands signaling through GPCRs. Mounting evidence of GPCR receptor heteromers indicates that the observable effects of ligands are the result of their actions on GPCR arrays arranged as heteromers (dimers or larger complexes of receptor units). These GPCR heteromeric arrays are now suggested as the primary targets for various ligands originally thought to target only single receptors. This theory is better suited to provide realistic explanations for complex problems that have been difficult to explain by classical pharmacological theory. GPCR heteromers, though accepted in the field as a standard signaling unit, have unusually little exposure and acceptance in the general scientific community. To better present their work on opioid receptor heteromers, and facilitate consumption and recognition of the concepts involved in GPCR heteromeric array based signaling, these researchers require molecularly accurate representations of the systems involved. They use MSI facilities and resources to produce accurate renderings of opioid receptor heteromers, the small molecules they design and synthesize that target them, and the signaling cascades that result from heteromer activation. These accurate images of the receptor heteromer system will provide elegant visual aids that will assist persons less familiar with the concepts involved in rapidly assimilating this complex knowledge base.

Group Members

Eyup Akgun, Research Associate
M. Irfan Javed, Research Associate
Morgan LeNaour, Research Associate
Mary Lunzer, Staff
Matthew D. Metcalf, Research Associate
Sri Kamesh Narasimhan, Research Associate