2gyd

Publication Abstract from PubMed

The difficulty in obtaining binding target and site information for low-affinity drugs, like the inhaled anesthetics, has limited identification of their molecular effectors. Because such information can be provided by photoactive analogues, we designed, synthesized, and characterized a novel diazirnyl haloether that closely mimics isoflurane, the most widely used clinical general anesthetic. This compound, H-diaziflurane, is a nontoxic, potent anesthetic that potentiates GABA-gated ion channels in primary cultures of hippocampal neurons. Calorimetric and structural characterizations show that H-diaziflurane binds a model anesthetic host protein with similar energetics as isoflurane and forms photoadducts with residues lining the isoflurane binding site. H-diaziflurane will be immediately useful for identifying targets and sites important for the molecular pharmacology of the inhaled haloether anesthetics.

Photoactive analogues of the haloether anesthetics provide high-resolution features from low-affinity interactions.,Xi J, Liu R, Rossi MJ, Yang J, Loll PJ, Dailey WP, Eckenhoff RG ACS Chem Biol. 2006 Jul 21;1(6):377-84. PMID:17163775^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.