Probing the Mode of Neurotransmitter Binding to GABA Receptors Using Selectively Fluorinated GABA Analogues

被引：10

作者：

Absalom, Nathan ^{[1
]}

Yamamoto, Izumi ^{[1
,2
]}

O'Hagan, David ^{[3
]}

Hunter, Luke ^{[4
]}

Chebib, Mary ^{[1
]}

机构：

[1] Univ Sydney, Fac Pharm, Sydney, NSW 2006, Australia

[2] Natl Inst Nat Sci, Natl Inst Physiol Sci, Dept Mol Physiol, Okazaki, Aichi 4448585, Japan

[3] Univ St Andrews, Sch Chem, St Andrews KY16 9ST, Fife, Scotland

[4] UNSW Australia, Sch Chem, Sydney, NSW 2052, Australia

来源：

AUSTRALIAN JOURNAL OF CHEMISTRY | 2015年 / 68卷 / 01期

基金：

英国工程与自然科学研究理事会;

关键词：

GATED ION-CHANNEL; X-RAY-STRUCTURE; B RECEPTOR; ACTIVATION; SUBUNITS; STOICHIOMETRY; PHARMACOLOGY; ENANTIOMERS; SUBTYPES; AGONIST;

D O I：

10.1071/CH14456

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Stereoselective fluorination is a useful technique for controlling the conformations of organic molecules. This concept has been exploited to create conformationally biased analogues of the neurotransmitter gamma-aminobutyric acid (GABA). Mono- and di-fluorinated GABA analogues are found to adopt different conformations, due to subtle stereoelectronic effects associated with the C-F bond. These conformationally biased GABA analogues exhibit different shape-dependent selectivity patterns towards GABA(A), GABA(B), and GABA(C) receptors, providing valuable information on the binding modes of the natural ligand at these medicinally important targets.

引用

页码：23 / 30

页数：8

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