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, Roderic G. Eckenhoff

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)377-384
Number of pages8
JournalACS chemical biology
Volume1
Issue number6
DOIs
Publication statusPublished - Jul 21 2006

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Medicine

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