Azi-isoflurane, a Photolabel Analog of the Commonly Used Inhaled General Anesthetic Isoflurane

• Published in: ACS chemical neuroscience 2010-02, Vol.1 (2), p.139-145
• Main Authors: Eckenhoff, Roderic G, Xi, Jin, Shimaoka, Motomu, Bhattacharji, Aditya, Covarrubias, Manuel, Dailey, William P
• Format: Article
• Language: English
• ISSN: 1948-7193; 1948-7193
• DOI: 10.1021/cn900014m

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.