title: Synthesis and characterization of photoaffinity probes that target the 5-HT3 receptor.
abstract: The 5-HT3 receptor is one of several ion channels responsible for the transmission of nerve impulses in the peripheral and central nervous systems. Until now, it has been difficult to characterize transmembrane receptors with classical structural biology approaches like X-ray crystallography. The use of photoaffinity probes is an alternative approach to identify regions in the protein where small molecules bind. To this end, we present two photoaffinity probes based on granisetron, a well known antagonist of the 5-HT3 receptor. These new probes show nanomolar binding affinity for the orthosteric binding site. In addition, we investigated their reactivity using irradiation experiments.
authors.affiliation: Universität Bern Departement für Chemie und Biochemie Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Jack
authors.affiliation: Universität Bern Departement für Chemie und Biochemie Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Marc-David
authors.initials: MD
authors.lastname: Ruepp
authors.affiliation: Universität Bern Departement für Chemie und Biochemie Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Thompson
authors.affiliation: Universität Bern Departement für Chemie und Biochemie Freiestrasse 3 CH-3012 Bern, Switzerland.
authors.forename: Oliver
authors.initials: O
authors.lastname: Mühlemann
authors.affiliation: Universität Bern Departement für Chemie und Biochemie Freiestrasse 3 CH-3012 Bern, Switzerland. martin.lochner@dcb.unibe.ch.
authors.forename: Martin
authors.initials: M
authors.lastname: Lochner
mesh_terms: D001665:Binding Sites; D003978:Diazomethane / Q000737:chemistry*; D017829:Granisetron / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D008024:Ligands; D008958:Models, Molecular; D019920:Photoaffinity Labels / Q000138:chemical synthesis / Q000737:chemistry*; D011485:Protein Binding; D044406:Receptors, Serotonin, 5-HT3 / Q000737:chemistry*; D012702:Serotonin Antagonists / Q000138:chemical synthesis / Q000737:chemistry*; D040681:Structural Homology, Protein; D014466:Ultraviolet Rays
chemical_list: D003978:Diazomethane; D017829:Granisetron; D008024:Ligands; D019920:Photoaffinity Labels; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists