title: Tactical Approaches to Interconverting GPCR Agonists and Antagonists.
abstract: There are many reported examples of small structural modifications to GPCR-targeted ligands leading to major changes in their functional activity, converting agonists into antagonists or vice versa. These shifts in functional activity are often accompanied by negligible changes in binding affinity. The current perspective focuses on outlining and analyzing various approaches that have been used to interconvert GPCR agonists, partial agonists, and antagonists in order to achieve the intended functional activity at a GPCR of therapeutic interest. An improved understanding of specific structural modifications that are likely to alter the functional activity of a GPCR ligand may be of use to researchers designing GPCR-targeted drugs and/or probe compounds, specifically in cases where a particular ligand exhibits good potency but not the preferred functional activity at the GPCR of choice.
authors.affiliation: Institute for Therapeutics Discovery and Development, Department of Medicinal Chemistry, University of Minnesota , 717 Delaware Street SE, Minneapolis, Minnesota 55414, United States.
authors.forename: Peter I
authors.initials: PI
authors.lastname: Dosa
authors.affiliation: Department of Medicinal Chemistry and Minnesota Supercomputing Institute for Advanced Computational Research, University of Minnesota , 717 Delaware Street SE, Minneapolis, Minnesota 55414, United States.
authors.forename: Elizabeth Ambrose
authors.initials: EA
authors.lastname: Amin
mesh_terms: D000818:Animals; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000819:agonists* / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
chemical_list: D008024:Ligands; D043562:Receptors, G-Protein-Coupled