Document Type
Article
Publication Date
2-17-2010
Abstract
Volatility and low-affinity hamper an ability to define molecular targets of the inhaled anesthetics. Photolabels have proven to be a useful approach in this regard, although none have closely mimicked contemporary drugs. We report here the synthesis and validation of azi-isoflurane, a compound constructed by adding a diazirinyl moiety to the methyl carbon of the commonly used general anesthetic isoflurane. Azi-isoflurane is slightly more hydrophobic than isoflurane, and more potent in tadpoles. This novel compound inhibits Shaw2 K(+) channel currents similarly to isoflurane and binds to apoferritin with enhanced affinity. Finally, when irradiated at 300 nm, azi-isoflurane adducts to residues known to line isoflurane-binding sites in apoferritin and integrin LFA-1, the only proteins with isoflurane binding sites defined by crystallography. This reagent should allow rapid discovery of isoflurane molecular targets and binding sites within those targets.
Recommended Citation
Eckenhoff, Roderic G; Xi, Jin; Shimaoka, Motomu; Bhattacharji, Aditya; Covarrubias, Manuel; and Dailey, William P, "Azi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane." (2010). Department of Pathology, Anatomy, and Cell Biology Faculty Papers. Paper 118.
https://jdc.jefferson.edu/pacbfp/118
PubMed ID
20228895
Comments
This article has been peer reviewed. It was published in: ACS chemical neuroscience
Volume 17, Issue 1, February 2010, Pages 139-145.
The published version is available at DOI: 10.1021/cn900014m. Copyright © ACS Publications