General synthesis of β-alanine-containing spider polyamine toxins and discovery of nephila polyamine toxins 1 and 8 as highly potent inhibitors of ionotropic glutamate receptors

Research output: Contribution to journalJournal articleResearchpeer-review

Simon Lucas, Mette H Poulsen, Niels G Nørager, Anne F Barslund, Tinna B Bach, Anders S Kristensen, Kristian Strømgaard

Certain spiders contain large pools of polyamine toxins, which are putative pharmacological tools awaiting further discovery. Here we present a general synthesis strategy for this class of toxins and prepare five structurally varied polyamine toxins. Electrophysiological testing at three ionotropic glutamate receptor subtypes reveals that two of these, Nephila polyamine toxins 1 (NPTX-1) and 8 (NPTX-8), comprise intriguing pharmacological activities by having subnanomolar IC(50) values at kainate receptors.
Original languageEnglish
JournalJournal of Medicinal Chemistry
Volume55
Issue number22
Pages (from-to)10297-10301
Number of pages5
ISSN0022-2623
DOIs
Publication statusPublished - 26 Nov 2012

    Research areas

  • Animals, Asparagine, Indoleacetic Acids, Molecular Structure, Polyamines, Receptors, Ionotropic Glutamate, Receptors, Kainic Acid, Spider Venoms, Spiders, Structure-Activity Relationship, Toxins, Biological, beta-Alanine

ID: 45806724