Photoactive analogues of the haloether anesthetics provide high-resolution features from low-affinity interactions.
Photoactive analogues of the haloether anesthetics provide high-resolution features from low-affinity interactions.
复制标题
卤醚麻醉剂的光活性类似物通过低亲和力相互作用提供高分辨率特征。
DOI：
10.1021/cb600207d
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发表时间：
2006
影响因子：
4
通讯作者：
Eckenhoff,RodericG
中科院分区：
文献类型：
--
作者：
Xi,Jin;Liu,Renyu;Rossi,MatthewJ;Yang,Jay;Loll,PatrickJ;Dailey,WilliamP;Eckenhoff,RodericG
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.
