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.
journal_name
Curr Top Med Chemjournal_title
Current topics in medicinal chemistryauthors
Vogensen SB,Greenwood JR,Bunch L,Clausen RPdoi
10.2174/156802611795164990subject
Has Abstractpub_date
2011-01-01 00:00:00pages
887-906issue
7eissn
1568-0266issn
1873-4294pii
BSP/CTMC/E-Pub/-00052-11-8journal_volume
11pub_type
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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journal_title:Current topics in medicinal chemistry
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