Referenced in: none

Automatically associated channels: Kv10.1

Title: Maleimide conjugates of saxitoxin as covalent inhibitors of voltage-gated sodium channels.

Authors: William H Parsons, J Du Bois

Journal, date & volume: J. Am. Chem. Soc., 2013 Jul 24 , 135, 10582-5

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/23855513

Abstract
(+)-Saxitoxin, a naturally occurring guanidinium poison, functions as a potent, selective, and reversible inhibitor of voltage-gated sodium ion channels (NaVs). Modified forms of this toxin bearing cysteine-reactive maleimide groups are available through total synthesis and are found to irreversibly inhibit sodium ion conductance in recombinantly expressed wild-type sodium channels and in hippocampal nerve cells. Our findings support a mechanism for covalent protein modification in which toxin binding to the channel pore precedes maleimide alkylation of a nucleophilic amino acid. Second-generation maleimide-toxin conjugates, which include bioorthogonal reactive groups, are also found to block channel function irreversibly; such compounds have potential as reagents for selective labeling of NaVs for live cell imaging and/or proteomics experiments.