Maitotoxin

3 Vannusal B Vannusal B, isolated from Euplotes vannus, was originally proposed to have the structure 25a.Subsequent synthetic and NMR studies have settled on 25b as its actual structure.  

Saelli et al. computed the chemical shifts of 25a, 25b, and six other diastere-omers at M06/pcS-2//B3LYP/6-31g(d,p). The computed chemical shifts of 25a poorly correlate with the experimental chemical shifts of vannusal B, with a low correlation coefficient of 0.9580 and a maximum error of 16.2 ppm. They point out that had DFT computations been performed in 1992, stracture 25a might never have 

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Complete structure of maitotoxin molecule, which includes 32 6-8-member 0-heterocycles as parts of fused systems linked by C—C bonds and 2-4-member carbon chains 98PAC339. 

Complete structure of maitotoxin, polycyclic saturated 0-heterocycle 97YGK535. 

A similar phenomenology attends the actions of maitotoxin, another large organic molecule that induces a Ca selective membrane permeability (see chapter by Ohizumi Kobayashi in this volume). None of the known inhibitors of Ca channels, including Co , Cd, dihydropyridines, and verapamil or diltiazem affect the maitotoxin-induced increase in Ca permeability. To date, an association between maitotoxin and an existing Ca pump or exchange protein has not been demonstrated. 

Figure 2. Negative FAB mass spectra of maitotoxin. The numbers denote the mass number at the centroid of each peak. A A survey scan at a low resolution (R=300). B. Resolution enhanced spectrum (R=3000) for ion clusters at around m/z 3300. C. Resolution enhanced spectrum (R=3000) for ion clusters at around miz 3400.

Figure 3. NMR-DEPT spectra of maitotoxin in CD3CN-D2O (1 1) A, methyls and methines appear as positive peaks and methylenes as negative peaks B, only methines appear C, no quarternary carbons appear and D, a conventional noise-decoupled spectrum.

Ca-Dependent Excitatory Effects of Maitotoxin on Smooth and Cardiac Muscle... 

Figure 1. The log cx)ncentration-cx)ntractile response curves for maitotoxin (MTX) in the rabbit aorta in the presence ( ) or absence (o) of verapamil (10" M). Verapamil was administered 15 min before the application of MTX. The maximum response to MTX (3 x 10 g/mL) is expressed as 100%. Vertical lines indicate the standard error of mean (n=7). (Reproduced with permission from Ref. 13. Copyright 1983 Press Syndicate of the University of Cambridge)...

Figure 4. Effect of maitotoxin (MTX, 2-6 x 10 g/mL) on the contractile response of guinea pig left (a) and right (b) atria. MTX was administered at the arrow. Numbers above the tracing indicate the times after the application of MTX. The horizontal calibration indicates 4 min for the tracing recorded at a slower sweep speed and 4 sec for that recorded at faster speed. (Reproduced with permission from Ref. 20. Copyright 1987 Elsevier)...

Figure 5. Effect of maitotoxin (MTX) on the contractile activity of cultured rat myocardial cells. The value (mean of three sets of experiments) is the percentage of arrhythmically beating myocytes among total moving cells (43-69 myocytes). MTX concentration used...

Figure 7. The log cxjncentration-response curve for maitotoxin (MTX) on the tissue Ca content of guinea pig left atria. Vertical lines indicate the standard error of mean (n=6). (Reproduced with permission from Ref. 14. Copyright 1985 Macmillan)...

Figure 9. Typical fluorescence signals obtained from a suspension of isolated rat cardiac myocytes after the application of maitotoxin (MTX). The arrow indicates the addition of MTX (10 g/mL), a detergent Emulgen 810 (1%), which frees all vesicular Ca , or EGTA (3.5 mM), a chelator that removes all free Ca in the cuvette. The intensity of Quin 2 fluorescence is expressed in arbitrary units. (Reproduced with permission from Ref. 20. Copyright 1987 Elsevier)...

We are grateful to Prof. T. Yasumoto of Tohoku University for generously supplying maitotoxin. We are indebted to Ms. Y. Murakami of this Institute for secretarial assistance. 

Cultures of Gambierdiscus toxicus have been obtained in several laboratories (14,17-19). These cultures produce large amounts of maitotoxin and low amounts of lipid-soluble CTx-like toxin. However, in most cases, this toxin has not been unequivocally identified as CTx. The only firm evidence that cultures of Gambierdiscus toxicus produce CTx was provided by Baden et al. (20) who used radioimmunoassays and electrophysiological experiments to characterize the toxin. It is possible that cultured Gambierdiscus toxicus produce only trace amounts of CTx and that levels of production comparable to those found in natural populations are dependent on yet undefined environmental parameters. 

This work was supported by Grant GM 27256 from the National Institutes of Health and Grant DA 02507 from the National Institute of Drug Abuse. LL. is an American Cancer Society Research Professor of Biochemistry (Award PRP-21). H.V.V. is the recipient of a Research Career Award (5K6-AI-2372) from the National Institute of Allergy and Infectious Disease. We thank Dr. Y. Hirata of Meijo University for generous gifts of palytoxin isolated from Palythoa tuberculosa. We thank Dr. T. Yasumoto, Tohoku University, Sendai, Japan, for the maitotoxin preparation. We thank also Jeffrey A. Bessette and Nancy Worth for their technical assistance and Inez Zimmerman for preparation of the manuscript. 

Chandrasekhar, J. "Maitotoxin—Holder of Two World Records." Resonance (May 1996) 68-70. 

Estacion, Mark, and William P. Schilling. "Maitotoxin-Induced Membrane Blebbing and Cell Death in Bovine Aortic Endothelial Cells." BMC Physiology 1 (2001) 2. 

Kishi, Yoshito. "Complete Structure of Maitotoxin." Pure Applied Chemistry 70 (1998) 339-44. 

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