m-Azipropofol (AziPm) a photoactive analogue of the intravenous general anesthetic propofol.
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.
Hall
Michael A
MA
Department of Anesthesiology and Critical Care, University of Pennsylvania School of Medicine, Philadelphia,Pennsylvania, USA.
Xi
Jin
J
Lor
Chong
C
Dai
Shuiping
S
Pearce
Robert
R
Dailey
William P
WP
Eckenhoff
Roderic G
RG
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
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