Heptapeptide toxins

Nodularia spwnigena has also been shown to produce a peptide with hepato-toxic activity. The more recent reports come from Australia (76), the German Democratic Republic (77), Denmark (78), Sweden (79), and Finland (80,81). Recently structure information on Nodularia toxin has been presented by Rinehart (97) for waterbloom material collected in Lake Forsythe, New Zealand, in 1984 by Eriksson et al. (81) from waterbloom material collected in the Baltic Sea in 1986, and Runnegar et al. (82) for a field isolate from the Peel Inlet, Perth, Australia. Structure work by Rinehart, Eriksson, and Runnegar all indicate that the peptide is smaller than the heptapeptide toxins. Rinehart s work (97) indicates the toxin is a pentapeptide with a similar structure to the heptapeptides and containing fi-methylaspartic acid, glutamic acid, arginine, dehydrobutyrine, and ADDA (MW 824). 

D.P. Botes, A.A. Tuinmann, P.L. Wessels, C.C. Viljoen, H. Kruger, D.H. Williams, S. Santikarn, R.J. Smith and S.J. Hammond, The structure of cyanoginosin-LA, a cyclic heptapeptide toxin from the cyanobacterium Microcystis aeruginosa, J. Chem. Soc. Perkin Trans., 1 (1984) 2311-2318. 

W.W. Carmichael, V. Beasley, D.L. Bunner, J.N. Eloff, I.R. Falconer, P. Gorham, K.-I. Harada, T. Krishnamurthy, Y. Min-Juan, R.E. Moore, K. Rinehart, M. Runnegar, O.M. Skulberg and M. Watanabe, Naming of cyclic heptapeptide toxins of cyanobacteria (blue-green algae), Toxicon, 26 (1988) 971-973. 

Carmichael, W.W, Beasley, V, Bunner, D.L., Eloff, IN., Ealconer, I., Gorham, P, Harada, K.-L, Krishnamurthy T, Min-Juan, Y, Moore, R.E., Rinehart, K., Runnegar, M., Skulberg, O.M., and Watanabe, M. 1988. Naming of cyclic heptapeptide toxins of cyanobacteria (blue-green algae). Toxicon 26 971-973. 

Vasconcelos, VM. 1995. Uptake and depuration of the heptapeptide toxin microcystin-LR in Mytilus galloprovincialis. 

Carmichael, W.W. et al., Naming of cychc heptapeptide toxins of cyanobacteria (blue-green algae),... 

Four cyclic heptapeptide toxins (extracted fixim Microceptis auruginosd) consisting of D-alanine, eryfAro-yJ-methylaspartic acid, glutamic acid, L-leucine, L-alanine, A -methyldehydroadenosine, and 3-amino-9-methoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dioenoic acid were baseline resolved in 20 min using a C g column (A = 238 nm) and a 58/42 methanol/water (50 mM phosphate buffer at pH 3) mobile phase [472]. Excellent peak shapes were obtained. 

Botes, D.R, Tuinman, A.A., Wessels, P.L., Viljoen, C.C., Kruger, H., Williams, D.H., Santikarn, S., Smith, R.J., and Hammonds, S., 1984, The Structure of Cyanoginosin-LA, a Cyclic Heptapeptide Toxin from the Cyanobacterium Microsystis aeruginosa. In J.Chem.Soc.Perkin Trans., 2311-2318... 

These natural toxins are heptapeptides produced by cyanobacteria, which are associated with algal blooms. These substances are a hazard to wild and farm animals and sometimes humans who come in contact with contaminated water. There are a number of these toxins, some of which such as microcystin LR are hepatotoxic, causing damage to both hepatocytes and endothelial cells. The toxins have some unusual structural features, incorporating three D-amino acids and two very unusual ones, namely, methyldehydro alanine (Mdha) and amino-methoxy-trimethyl-phenyl-decadi-enoic acid (Adda) (Fig. 7.26). 

These natural toxins are heptapeptides produced by cyanobacteria and have unusual structural features, incorporating three D-amino acids. Microcystin LR is hepatotoxic, as a result of inactivation of protein phosphatases, which leads to breakdown of the cytoskeleton and cell death. 

The first chemical stractures of cyanobacterial cyclic peptide toxins were identified in the early 1980s and the number of fully characterized toxin variants has greatly increased since the 1990s. To-date there are 77 different microcystins isolated from cyanobacteria (Table 40.3). The first such compounds found in freshwater cyanobacteria were cyclic heptapeptides with the general stracture of cyclo-(D-alanine -X -D-MeAsp -Z" -Adda -D-Glutamate -Mdha ) in which X and Z are variable amino acids, o-MeAsp is D-eryt/jro-p-methylaspartic acid, and Mdha is A-methyldehydroalanine (Eigure 40.1a). The amino acid Adda, (2S, 3S, 8S, 9S)-3-amino-9-methoxy-2,6,8- trimethyl-10-phenyldeca-4,6-dienoic acid, is the most unusual structural moiety in... 

The extremely poisonous green mushroom Amanita phalloides contains a number of cyclic peptides classified as phallotoxins (heptapeptides), ama-toxins (octapeptides), and a decapeptide antagonist called antamanide (Wieland and Wieland, 1972). Crystal structure analyses have been completed on jS-amanitin, on antamanide, and on a biologically active analog, both com-plexed and uncomplexed. 

Virotoxins. A group of monocyclic heptapeptides from the toadstool Amanita vimsa (destroying angel). Together with the amanitins and phallotoxins, they represent the third class of poisons in death caps. Six compounds are known viroisin is the main toxin. 

Studies in several laboratories have shown that strongly hepatotoxic cyclic heptapeptides of a common type occur in different strains of Microcystis [59]. Microcystis aeruginosa, the species most frequently investigated contains the peptide formulated in Fig. 25. The two letter suffix LA designates the two L-amino acids in positions 2 and 4 (X, Y = Leu, Ala) which have been found variable in all of the toxins examined to date. X can also be arginine (R) or methionine (M). The 10-carbon chain jS-amino acid is unique for this type of hepatotoxic compound. Another not quite common structural element is the unsaturated side chain of dehydroalanine (No. 7), the formation of which can readily be imagined by elimination of H2O from serine or H2S from cysteine. 

Determination of microcystins (MC) has gained, in last two decades, a great interest because of the related ecological and public health risks. They are toxins which are produced and accumulated within the freshwater cyanobacterial algae during their blooming, and then enter the aquatic environment after cell lysis.Over 70 different analogs of microcystins have been isolated from natural blooms and laboratory cultures of cyanobacteria. " Chemically, MC are cyclic heptapeptides, composed of five invariable and two variable amino acids (Scheme 1). 

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