Student News

Molecule of the Week – Maitotoxin

Ivory Hills – October 28, 2011

Maitotoxin (MTX) is an extremely potent toxin produced by the dinoflagellate Gambierdiscus toxicus. The toxin has been known to work its way into the human food chain (seafood) and has led to extreme illness and death.  Toxicity studies have been conducted demonstrating lethality in mice at a dose of approximately 0.00013 milligrams per kilogram of subject. As a point of comparison please note that a standard dose of Tylenol is approximately 13 milligrams per kilogram. This toxin can cause an irreversible pharmacological response (death) at a dose that is 100,000 times lower than the most commonly used painkiller – Maitotoxin is bad news! 

Despite this unsavory side to MTX’s biochemical profile, there is intense interest to further study this compound.  The mode of toxicity is believed to be via the formation of  ion channels in the cellular membrane.  To-date humans do not know how to intentionally achieve this process in any useful fashion.  Potential breakthroughs in the areas of neuronal signaling or drug delivery could arise from better understanding MTX’s ability to form ion channels.

Toward this end research groups are attempting to perform the total synthesis of this compound, since the dinoflagellate natural source is difficult to isolate and only provides minuscule quantities of this compound.  Major players in this area include the research teams of K.C. Nicolaou at the Scripps Research Institute in California, Yoshito Kishi at Harvard University and Tadashi Nakata at the RIKEN Institute in Japan.  These chemists have been working for over a decade on the synthesis of MTX and the struggle continues.

If you’re interested then think about . . .

1. How do you think maitotoxin can form pores in a cellular membrane?  Is there some significance to the structure above having a “u-turn”?

2. Does this molecule have the features that would allow it to interact with a cellular membrane (non-polar in the lipid bilayer and polar on the inner and outer surface)?

3. Can you determine what the average thickness of a cellular membrane is?  What is the length of a single molecule of maitotoxin?  Can it physically span a cellular membrane?