Citation

Thottumkara AP, Parsons WH, Du Bois J. Angew Chem. Int. Ed. Engl. 2014; 53(23): 5760-5784.

Affiliation

Department of Chemistry, Stanford University, Stanford, CA 94305-5080 (USA).

Copyright

(Copyright © 2014, Wiley-VCH)

DOI

10.1002/anie.201308235

PMID

24771635

Abstract

The paralytic agent (+)-saxitoxin (STX), most commonly associated with oceanic red tides and shellfish poisoning, is a potent inhibitor of electrical conduction in cells. Its nefarious effects result from inhibition of voltage-gated sodium channels (NaV s), the obligatory proteins responsible for the initiation and propagation of action potentials. In the annals of ion channel research, the identification and characterization of NaV s trace to the availability of STX and an allied guanidinium derivative, tetrodotoxin. The mystique of STX is expressed in both its function and form, as this uniquely compact dication boasts more heteroatoms than carbon centers. This Review highlights both the chemistry and chemical biology of this fascinating natural product, and offers a perspective as to how molecular design and synthesis may be used to explore NaV structure and function.

Language: en