Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from Nephila clavata

Anne Fuglsang Barslund; Mette Homann Poulsen; Tinna Brøbech Bach; Simon Lucas; Anders Skov Kristensen; Kristian Strømgaard

doi:10.1021/np100746w

Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from Nephila clavata

Anne Fuglsang Barslund, Mette Homann Poulsen, Tinna Brøbech Bach, Simon Lucas, Anders Skov Kristensen, Kristian Strømgaard

8 Citationer (Scopus)

Abstract

Polyamine toxins from orb weaver spiders are attractive pharmacological tools particularly for studies of ionotropic glutamate (iGlu) receptors in the brain. These polyamine toxins are biosynthesized in a combinatorial manner, providing a plethora of related, but structurally complex toxins to be exploited in biological studies. Here, we have used solid-phase synthetic methodology for the efficient synthesis of Joro spider toxin-4 (JSTX-4) (1) from Nephila clavata, providing sufficient amounts of the toxin for biological evaluation at iGlu receptor subtypes using electrophysiology. Biological evaluation revealed that JSTX-4 inhibits iGlu receptors only in high µM concentrations, thereby being substantially less potent than structurally related polyamine toxins.

Originalsprog	Engelsk
Tidsskrift	Journal of Natural Products
Vol/bind	74
Udgave nummer	3
Sider (fra-til)	483-486
ISSN	0163-3864
DOI	https://doi.org/10.1021/np100746w
Status	Udgivet - 25 mar. 2011

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author = "Barslund, {Anne Fuglsang} and Poulsen, {Mette Homann} and Bach, {Tinna Br{\o}bech} and Simon Lucas and Kristensen, {Anders Skov} and Kristian Str{\o}mgaard",

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T1 - Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from Nephila clavata

AU - Barslund, Anne Fuglsang

AU - Poulsen, Mette Homann

AU - Bach, Tinna Brøbech

AU - Lucas, Simon

AU - Kristensen, Anders Skov

AU - Strømgaard, Kristian

PY - 2011/3/25

Y1 - 2011/3/25

N2 - Polyamine toxins from orb weaver spiders are attractive pharmacological tools particularly for studies of ionotropic glutamate (iGlu) receptors in the brain. These polyamine toxins are biosynthesized in a combinatorial manner, providing a plethora of related, but structurally complex toxins to be exploited in biological studies. Here, we have used solid-phase synthetic methodology for the efficient synthesis of Joro spider toxin-4 (JSTX-4) (1) from Nephila clavata, providing sufficient amounts of the toxin for biological evaluation at iGlu receptor subtypes using electrophysiology. Biological evaluation revealed that JSTX-4 inhibits iGlu receptors only in high µM concentrations, thereby being substantially less potent than structurally related polyamine toxins.

AB - Polyamine toxins from orb weaver spiders are attractive pharmacological tools particularly for studies of ionotropic glutamate (iGlu) receptors in the brain. These polyamine toxins are biosynthesized in a combinatorial manner, providing a plethora of related, but structurally complex toxins to be exploited in biological studies. Here, we have used solid-phase synthetic methodology for the efficient synthesis of Joro spider toxin-4 (JSTX-4) (1) from Nephila clavata, providing sufficient amounts of the toxin for biological evaluation at iGlu receptor subtypes using electrophysiology. Biological evaluation revealed that JSTX-4 inhibits iGlu receptors only in high µM concentrations, thereby being substantially less potent than structurally related polyamine toxins.

KW - Former Faculty of Pharmaceutical Sciences

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DO - 10.1021/np100746w

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SN - 0163-3864

VL - 74

SP - 483

EP - 486

JO - Journal of Natural Products

JF - Journal of Natural Products

IS - 3

ER -

Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from Nephila clavata

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