title: m-Azipropofol (AziPm) a photoactive analogue of the intravenous general anesthetic propofol.
abstract: Propofol is the most commonly used sedative-hypnotic drug for noxious procedures, yet the molecular targets underlying either its beneficial or toxic effects remain uncertain. In order to determine targets and thereby mechanisms of propofol, we have synthesized a photoactivateable analogue by substituting an alkyldiazirinyl moiety for one of the isopropyl arms but in the meta position. m-Azipropofol retains the physical, biochemical, GABA(A) receptor modulatory, and in vivo activity of propofol and photoadducts to amino acid residues in known propofol binding sites in natural proteins. Using either mass spectrometry or radiolabeling, this reagent may be used to reveal sites and targets that underlie the mechanism of both the desirable and undesirable actions of this important clinical compound.
authors.affiliation: Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Hall
authors.forename: Jin
authors.initials: J
authors.lastname: Xi
authors.forename: Chong
authors.initials: C
authors.lastname: Lor
authors.forename: Shuiping
authors.initials: S
authors.lastname: Dai
authors.forename: Robert
authors.initials: R
authors.lastname: Pearce
authors.forename: William P
authors.initials: WP
authors.lastname: Dailey
authors.forename: Roderic G
authors.initials: RG
authors.lastname: Eckenhoff
mesh_terms: D018686:Anesthetics, Intravenous / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001052:Apoferritins / Q000737:chemistry; D002460:Cell Line; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D004594:Electrophysiology; D006736:Horses; D006801:Humans; D006993:Hypnotics and Sedatives / Q000138:chemical synthesis* / Q000494:pharmacology; D007814:Larva; D008958:Models, Molecular; D009043:Motor Activity / Q000187:drug effects; D019920:Photoaffinity Labels / Q000138:chemical synthesis* / Q000494:pharmacology; D015742:Propofol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D011485:Protein Binding; D021122:Protein Subunits / Q000502:physiology; D011963:Receptors, GABA-A / Q000502:physiology; D013216:Reflex, Startle / Q000187:drug effects; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: C551949:2-isopropyl-5-(3-(trifluoromethyl)-3H-diazirin-3-yl)phenol; D018686:Anesthetics, Intravenous; D006993:Hypnotics and Sedatives; D019920:Photoaffinity Labels; D021122:Protein Subunits; D011963:Receptors, GABA-A; D003978:Diazomethane; D001052:Apoferritins; D015742:Propofol