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

Nathan Absalom; Izumi Yamamoto; David O'Hagan; Luke Hunter; Mary Chebib

doi:10.1071/CH14456

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

Nathan Absalom
, Izumi Yamamoto
, David O'Hagan
, Luke Hunter
, Mary Chebib

The University of Sydney
National Institutes of Natural Sciences - National Institute for Physiological Sciences
University of St Andrews
University of New South Wales

Research output: Contribution to journal › Article › peer-review

13 Citations (Scopus)

Abstract

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.

Original language	English
Pages (from-to)	23-30
Number of pages	8
Journal	Australian Journal of Chemistry
Volume	68
Issue number	1
DOIs	https://doi.org/10.1071/CH14456
Publication status	Published - 2015
Externally published	Yes

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Publisher Copyright:
© CSIRO 2015.

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abstract = "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 GABAA, GABAB, and GABAC receptors, providing valuable information on the binding modes of the natural ligand at these medicinally important targets.",

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AU - Hunter, Luke

AU - Chebib, Mary

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AB - 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 GABAA, GABAB, and GABAC receptors, providing valuable information on the binding modes of the natural ligand at these medicinally important targets.

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

Abstract

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