2. Academic Validation
  3. 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

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

  • J Med Chem. 2012 Nov 26;55(22):10297-301. doi: 10.1021/jm301255m.
Simon Lucas 1,  Mette H Poulsen,  Niels G Nørager,  Anne F Barslund,  Tinna B Bach,  Anders S Kristensen,  Kristian Strømgaard
Affiliations

Affiliation

  • 1 Department of Drug Design and Pharmacology, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
PMID: 23092360 DOI: 10.1021/jm301255m
Abstract

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.

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