Glutamate receptor agonists: stereochemical aspects

Research output: Contribution to journalReviewResearchpeer-review

Stine Byskov Vogensen, Jeremy R Greenwood, Lennart Bunch, Rasmus Prætorius Clausen

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 a-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.
Original languageEnglish
JournalCurrent Topics in Medicinal Chemistry
Volume11
Issue number7
Pages (from-to)887-906
ISSN1568-0266
DOIs
Publication statusPublished - Apr 2011

ID: 33265460