A physicogenetic method to assign ligand-binding relationships between 7TM receptors.
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.
7TM Pharma A/S, Fremtidsvej 3, DK-2970 Hørsholm, Denmark.
Thomas M
TM
Frimurer
Trond
T
Ulven
Christian E
CE
Elling
Lars-Ole
LO
Gerlach
Evi
E
Kostenis
Thomas
T
Högberg
D000818:Animals; D001562:Benzimidazoles / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects; D001713:Biphenyl Compounds; D002417:Cattle; D003198:Computer Simulation; D015195:Drug Design; D006841:Hydrocarbons, Aromatic / Q000494:pharmacology*; D007213:Indomethacin / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D008954:Models, Biological; D015394:Molecular Structure; D043562:Receptors, G-Protein-Coupled / Q000037:antagonists & inhibitors* / Q000145:classification / Q000378:metabolism; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000378:metabolism; D011982:Receptors, Prostaglandin / Q000037:antagonists & inhibitors / Q000378:metabolism; D012243:Rhodopsin / Q000737:chemistry*; D013329:Structure-Activity Relationship; D013777:Tetrazoles / Q000737:chemistry / Q000494:pharmacology
D001562:Benzimidazoles; D001713:Biphenyl Compounds; D006841:Hydrocarbons, Aromatic; D008024:Ligands; D043562:Receptors, G-Protein-Coupled; D011971:Receptors, Immunologic; D011982:Receptors, Prostaglandin; D013777:Tetrazoles; D012243:Rhodopsin; C081643:candesartan; D007213:Indomethacin; C036293:prostaglandin D2 receptor