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

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

doi:10.1021/jm301255m

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

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

8 Citations (Scopus)

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.

Original language	English
Journal	Journal of Medicinal Chemistry
Volume	55
Issue number	22
Pages (from-to)	10297-10301
Number of pages	5
ISSN	0022-2623
DOIs	https://doi.org/10.1021/jm301255m
Publication status	Published - 26 Nov 2012

Keywords

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

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Lucas, S., Poulsen, M. H., Nørager, N. G., Barslund, A. F., Bach, T. B., Kristensen, A. S., & Strømgaard, K. (2012). 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. Journal of Medicinal Chemistry, 55(22), 10297-10301. https://doi.org/10.1021/jm301255m

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. / Lucas, Simon; Poulsen, Mette H; Nørager, Niels G et al.
In: Journal of Medicinal Chemistry, Vol. 55, No. 22, 26.11.2012, p. 10297-10301.

Research output: Contribution to journal › Journal article › Research › peer-review

Lucas, S, Poulsen, MH, Nørager, NG, Barslund, AF, Bach, TB, Kristensen, AS & Strømgaard, K 2012, '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', Journal of Medicinal Chemistry, vol. 55, no. 22, pp. 10297-10301. https://doi.org/10.1021/jm301255m

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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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AU - Barslund, Anne F

AU - Bach, Tinna B

AU - Kristensen, Anders S

AU - Strømgaard, Kristian

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KW - Asparagine

KW - Indoleacetic Acids

KW - Molecular Structure

KW - Polyamines

KW - Receptors, Ionotropic Glutamate

KW - Receptors, Kainic Acid

KW - Spider Venoms

KW - Spiders

KW - Structure-Activity Relationship

KW - Toxins, Biological

KW - beta-Alanine

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ER -

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

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Keywords

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