A physicogenetic method to assign ligand-binding relationships between 7TM receptors

• Published in: Bioorganic & medicinal chemistry letters 2005-08, Vol.15 (16), p.3707-3712
• Main Authors: Frimurer, Thomas M., Ulven, Trond, Elling, Christian E., Gerlach, Lars-Ole, Kostenis, Evi, Högberg, Thomas
• Format: Article
• Language: English
• Subjects: Animals; Benzimidazoles - chemistry; Benzimidazoles - pharmacology; Binding Sites - physiology; Binding, Competitive - drug effects; Cattle; Computer Simulation; Drug Design; Hydrocarbons, Aromatic - pharmacology; Indomethacin - analogs & derivatives; Indomethacin - chemistry; Indomethacin - pharmacology; Ligands; Models, Biological; Molecular Structure; Receptors, G-Protein-Coupled - antagonists & inhibitors; Receptors, G-Protein-Coupled - classification; Receptors, G-Protein-Coupled - metabolism; Receptors, Immunologic - antagonists & inhibitors; Receptors, Immunologic - metabolism; Receptors, Prostaglandin - antagonists & inhibitors; Receptors, Prostaglandin - metabolism; Rhodopsin - chemistry; Structure-Activity Relationship; Tetrazoles - chemistry; Tetrazoles - pharmacology
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2005.05.102

A computational protocol has been devised to relate 7TM receptor proteins (GPCRs) with respect to physicochemical features of the core ligand-binding site. A case targeting the newly identified prostaglandin D2 receptor CRTH2 serves as a primary example to illustrate the procedure. A computational protocol has been devised to relate 7TM receptor proteins (GPCRs) with respect to physicochemical features of the core ligand-binding site as defined from the crystal structure of bovine rhodopsin. The identification of such receptors that already are associated with ligand information (e.g., small molecule ligands with mutagenesis or SAR data) is used to support structure-guided drug design of novel ligands. A case targeting the newly identified prostaglandin D2 receptor CRTH2 serves as a primary example to illustrate the procedure.