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Photoactive analogues of the haloether anesthetics provide high-resolution features from low-affinity interactions
Journal article   Peer reviewed

Photoactive analogues of the haloether anesthetics provide high-resolution features from low-affinity interactions

Jin Xi, Renyu Liu, Matthew J Rossi, Jay Yang, Patrick J Loll, William P Dailey and Roderic G Eckenhoff
ACS chemical biology, v 1(6), pp 377-384
21 Jul 2006
PMID: 17163775

Abstract

Dose-Response Relationship, Drug Xenopus Anesthetics, Inhalation - chemistry Photoaffinity Labels - metabolism Animals Anesthetics - chemistry Anesthetics - metabolism Anesthetics, Inhalation - metabolism Binding Sites - physiology Cells, Cultured Calorimetry Photoaffinity Labels - chemistry
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.

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Collaboration types
Domestic collaboration
Web of Science research areas
Biochemistry & Molecular Biology
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