Saxitoxin [BSA]

Saxitoxin (STX), a bis-guanidinium small molecule produced by brackish and freshwater cyanobacteria and oceanic dinoflagelates associated with red tides, is one of the most lethal neurotoxins, causes paralytic shellfish poisoning (PSP), is a potent inhibitor of electrical conduction in cells. Its toxicity is thought to arise primarily from inhibition of select voltage-gated sodium channel (NaV) isoforms, although STX may affect other channels and enzymes. PSP caused by STX represents a notable public health and commercial hazard that is an increasing problem due to climate change. Consequently, shellfish for human consumption are monitored globally for PSP toxins. There is great interest in developing better analytical techniques for measuring STX and related cogeners in food sources. STX is an alkaloid with the molecular formula C10H17N7O4 (Molecular Weight = 299) and is composed of a 3,4-propinoperhydropurine tricyclic system. STX belongs to the large family of guanidinium-containing marine natural products, due to the presence of two guanidino groups which are responsible for its high polarity. The mystique of STX is expressed in both its function and form, as this uniquely compact dication boasts more heteroatoms than carbon centers.

Figure 1. Saxitoxin
(Source: Angew. Chem. Int. Ed. 2014)

Nature uses diverse strategies to counter toxin exposure that include target protein resistance mutations, toxin sequestration, and toxin removal. Saxiphilin (Sxph), a 91-kDa transferrin homolog, is an STX-binding protein from American bullfrog (Rana catesbeiana) heart and plasma. This soluble, dual-function protein has a single high-affinity STX-binding site [Kd (dissociation constant), ~0.2 nM] that recognizes certain STX derivatives and has two ~60 residue thyroglobulin type I (Thy1) repeats that act as potent [Ki (inhibition constant), ~1 nM] cysteine protease inhibitors. Other soluble STX-binding proteins have been identified in pufferfish, cockles, and crabs, and STX-binding activity has been reported in the plasma, hemolymph, and tissues from arthropods, amphibians, fish, and reptiles.