title: Solid-phase synthesis and biological evaluation of Joro spider toxin-4 from Nephila clavata.
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.
authors.affiliation: Department of Medicinal Chemistry, University of Copenhagen, Universitetsparken 2, DK-2100 Copenhagen, Denmark.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Barslund
authors.forename: Mette H
authors.initials: MH
authors.lastname: Poulsen
authors.forename: Tinna B
authors.initials: TB
authors.lastname: Bach
authors.forename: Simon
authors.initials: S
authors.lastname: Lucas
authors.forename: Anders S
authors.initials: AS
authors.lastname: Kristensen
authors.forename: Kristian
authors.initials: K
authors.lastname: Strømgaard
mesh_terms: D000818:Animals; D005260:Female; D007210:Indoleacetic Acids / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D015394:Molecular Structure; D009865:Oocytes / Q000187:drug effects; D011073:Polyamines / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D017470:Receptors, Glutamate / Q000187:drug effects*; D013111:Spider Venoms / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014982:Xenopus laevis
chemical_list: D007210:Indoleacetic Acids; C044936:JSTX spider toxin; C558367:JSTX-4 spider toxin; D011073:Polyamines; D017470:Receptors, Glutamate; D013111:Spider Venoms; C558368:argiotoxin-636