Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
J Nat Prod. 2011 Mar 25;74(3):483-6. doi: 10.1021/np100746w. Epub 2010 Dec 28.
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.
从圆蛛科蜘蛛中提取的多胺毒素是一种极具吸引力的药理学工具，特别适用于研究大脑中的离子型谷氨酸（iGlu）受体。这些多胺毒素以组合的方式生物合成，为生物研究提供了大量相关但结构复杂的毒素。在这里，我们使用固相合成方法从 Nephila clavata 中高效合成 Joro 蜘蛛毒素-4（JSTX-4）（1），为使用电生理学在 iGlu 受体亚型上进行生物评估提供了足够数量的毒素。生物评估表明，JSTX-4 仅在高 μM 浓度下抑制 iGlu 受体，因此其效力明显低于结构相关的多胺毒素。
