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Research Abstracts Online
January 2010 - March 2011

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

PI: Philip S. Portoghese

Interaction of Ligands With 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 initiate a signaling cascade upon activation of a single receptor unit. However, increasing evidence over the past decade has called into question the single receptor signaling unit concept as an overly simplistic representation of the actions of ligands signaling through GPCRs. Mounting evidence indicates that the observable effects of ligands are the result of their actions on GPCR arrays arranged as heteromers (larger complexes of receptor units). These GPCR heteromeric arrays are now suggested as the primary targets for various ligands originally thought to activate only single receptors. The existence of heteromers as targets for drugs is better suited to provide a more realistic explanation for complex structure-activity relationships that are difficult to explain by classical pharmacological theory. GPCR heteromers, though gaining increased acceptance in the field as standard signaling units, have had minimal exposure and acceptance in the general scientific community.

To assist in their research on opioid receptor heteromers, and facilitate analysis of the interaction of ligands with opioid GPCR heteromers, these researchers are using MSI’s facilities and resources. The small molecules they have synthesized that target these heteromers, and the signaling that arises from heteromer activation, should provide insight into the complexities associated with GPCR recognition by opioid ligands.

Group Members

Eyup Akgun, Research Associate
Jignesh Doshi, Research Associate
M. Irfan Javed, Research Associate
Morgan LeNaour, Research Associate
Mary Lunzer, Staff
Matthew D. Metcalf, Research Associate
Sri Kamesh Narasimhan, Research Associate
Michael Powers, Staff
Ajay Yekkirala, Graduate Student