title: Synthesis of the non-peptidic snail toxin 6-bromo-2-mercaptotryptamine dimer (BrMT)(2), its lower and higher thio homologs and their ability to modulate potassium ion channels.
abstract: The first synthesis of the non-peptidic snail toxin 6-bromo-2-mercaptotryptamine dimer (BrMT)2 is described, along with the preparation of its lower and higher thio homologs. The synthetic (BrMT)2 and its derivatives reported herein are all capable of slowing the activation of the Kv1.1 potassium ion channel. Only the monosulfide variant shows significant slowing of the deactivation process. This synthetic strategy can now be applied to creating a more extensive set of compounds that vary in the length of the linker connecting the two monomers, the substituents on the indole ring core, and terminal amine.
authors.affiliation: Department of Chemistry, Centennial Centre for Multidisciplinary Science, University of Alberta, Edmonton, Alberta T6G 2G2, Canada.
authors.forename: Detian
authors.initials: D
authors.lastname: Gao
authors.forename: Rheanna
authors.initials: R
authors.lastname: Sand
authors.forename: Hao
authors.initials: H
authors.lastname: Fu
authors.forename: Nazlee
authors.initials: N
authors.lastname: Sharmin
authors.forename: Warren J
authors.initials: WJ
authors.lastname: Gallin
authors.forename: Dennis G
authors.initials: DG
authors.lastname: Hall
mesh_terms: D000818:Animals; D019281:Dimerization; D051662:Kv1.1 Potassium Channel / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051379:Mice; D033661:Oocysts / Q000187:drug effects / Q000378:metabolism; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D012908:Snails / Q000378:metabolism; D014118:Toxins, Biological / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014363:Tryptamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014982:Xenopus laevis / Q000254:growth & development / Q000378:metabolism
chemical_list: D026902:Potassium Channel Blockers; D014118:Toxins, Biological; D014363:Tryptamines; D051662:Kv1.1 Potassium Channel; C030820:tryptamine
keywords: Electrophysiology; Indoles; Ion channel inhibitors; Natural products; Thiolation