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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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; Barslund, Anne F; Bach, Tinna B; Kristensen, Anders S; Strømgaard, Kristian.
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
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TY - JOUR
T1 - 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
AU - Lucas, Simon
AU - Poulsen, Mette H
AU - Nørager, Niels G
AU - Barslund, Anne F
AU - Bach, Tinna B
AU - Kristensen, Anders S
AU - Strømgaard, Kristian
PY - 2012/11/26
Y1 - 2012/11/26
N2 - 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.
AB - 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.
KW - Animals
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
U2 - 10.1021/jm301255m
DO - 10.1021/jm301255m
M3 - Journal article
C2 - 23092360
VL - 55
SP - 10297
EP - 10301
JO - Journal of Medicinal Chemistry
JF - Journal of Medicinal Chemistry
SN - 0022-2623
IS - 22
ER -
ID: 45806724