Synthesis and biological activity of argiotoxin 636 and analogues: selective antagonists for ionotropic glutamate receptors

Angew Chem Int Ed Engl. 2009;48(17):3087-91. doi: 10.1002/anie.200805426.

Abstract

More discerning than the parent: Analogues of the polyamine toxin argiotoxin 636 (shown docked in the ion channel of an ionotropic glutamate (iGlu) receptor; N blue, O red) distinguish subtypes of iGlu receptors. Depending on which of the two internal amine groups is replaced with a methylene group, the analogue inhibits one or other of two receptor subtypes as potently as the natural compound, which itself inhibits both subtypes nonselectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Excitatory Amino Acid Antagonists / chemical synthesis*
  • Excitatory Amino Acid Antagonists / chemistry
  • Excitatory Amino Acid Antagonists / pharmacology*
  • Indoleacetic Acids
  • Phenylacetates / chemical synthesis*
  • Phenylacetates / chemistry
  • Phenylacetates / pharmacology*
  • Polyamines / chemical synthesis*
  • Polyamines / chemistry
  • Polyamines / pharmacology*
  • Protein Conformation
  • Receptors, AMPA / antagonists & inhibitors*
  • Receptors, AMPA / chemistry
  • Receptors, N-Methyl-D-Aspartate / antagonists & inhibitors*
  • Receptors, N-Methyl-D-Aspartate / chemistry

Substances

  • Excitatory Amino Acid Antagonists
  • Indoleacetic Acids
  • Phenylacetates
  • Polyamines
  • Receptors, AMPA
  • Receptors, N-Methyl-D-Aspartate
  • argiotoxin-636