Abstract
The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally α-amino acids with one or more stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist binding pocket is filled, but also how it affects the conformational space of the ligand and in this way restricts the recognition of various glutamate receptors, ultimately leading to selectivity.
Keywords: Agonist, glutamate, ionotropic, metabotropic, stereochemistry, selectivity, X-ray structures, neurotransmitter (S)-glutamate [(S)-Glu], neurotransmission, agonist binding pocket, counterbalanced, synaptic plasticity, influx
Current Topics in Medicinal Chemistry
Title: Glutamate Receptor Agonists: Stereochemical Aspects
Volume: 11 Issue: 7
Author(s): Stine Byskov Vogensen, Jeremy R. Greenwood, Lennart Bunch and Rasmus Praetorius Clausen
Affiliation:
Keywords: Agonist, glutamate, ionotropic, metabotropic, stereochemistry, selectivity, X-ray structures, neurotransmitter (S)-glutamate [(S)-Glu], neurotransmission, agonist binding pocket, counterbalanced, synaptic plasticity, influx
Abstract: The neurotransmitter (S)-glutamate [(S)-Glu] is responsible for most of the excitatory neurotransmission in the central nervous system. The effect of (S)-Glu is mediated by both ionotropic and metabotropic receptors. Glutamate receptor agonists are generally α-amino acids with one or more stereogenic centers due to strict requirements in the agonist binding pocket of the activated state of the receptor. By contrast, there are many examples of achiral competitive antagonists. The present review addresses how stereochemistry affects the activity of glutamate receptor ligands. The review focuses mainly on agonists and discusses stereochemical and conformational considerations as well as biostructural knowledge of the agonist binding pockets, which is useful in the design of glutamate receptor agonists. Examples are chosen to demonstrate how stereochemistry not only determines how the agonist binding pocket is filled, but also how it affects the conformational space of the ligand and in this way restricts the recognition of various glutamate receptors, ultimately leading to selectivity.
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Cite this article as:
Byskov Vogensen Stine, R. Greenwood Jeremy, Bunch Lennart and Praetorius Clausen Rasmus, Glutamate Receptor Agonists: Stereochemical Aspects, Current Topics in Medicinal Chemistry 2011; 11 (7) . https://dx.doi.org/10.2174/156802611795164990
DOI https://dx.doi.org/10.2174/156802611795164990 |
Print ISSN 1568-0266 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4294 |

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