Peptydowe toksyny cyjanobakterii

This review presents chemical and biological aspects of secondary metabolites produced by cyanobacteria. The main goal of the work was to present studies related to microcystins and nodularins. Cyanobacteria (blue-green algae) growing both in freshwater and marine environment release to the medium numerous secondary metabolites. Some of cyanobacteria produce lethal toxins (cytotoxins and biotoxins). Therefore, cyanobacteria can be harmful for mammals, birds and fish, and also cause effects on human health. The secondary metabolites are the mostly derivatives of amino acids and peptides or depsipeptides. The best described among cyanobacteria toxins are the hepatotoxins: microcystins and nodularins. These toxins cause severe intrahepatic haemorrhage and hypovolaemic shock, and act as tumor promoters. Microcystins and nodularins are potent inhibitors of PP1 and PP2A protein phosphatases. Microcystins and nodularins, which are cyclic hepta- or penta-peptides, respectively, consists of various uncoded amino acid residues. The most characteristic and unique amino acid residue is Adda [(2S,3S,8S,9S,4E,6E)-3-amino-9-metoxy-2,6,8-trimethyl-10-phenyl-deca-4,6-dienoic acid]. Typical isolation of these toxins is realized by extraction combined with reversed-phase chromatography. Structure-activity relationship studies of microcystins and nodularins have revealed indispensability of Adda moiety, and two carboxyl groups of aspartic and glutamic acids, for the activity towards phosphatases. The total synthesis of both toxins represents quite a big challenge because of the necessity of preparation of Adda, as well as many other uncoded amino acids (D-erythro-b-methyl-aspartic acid, Masp; dehydroalanine, Dha, or dehydrobutyrine, Dhb, and their N-methyl derivatives etc.) prior to a final cyclization. Syntheses of Adda, the compound with four chiral centers and two specific configurations at the double bonds, were carried out mostly by the condensation of the previously obtained C1-C4 and C5-C10 fragments. Microcystins and nodularins are quite stable compounds in aqueous solution. They can be destroyed and removed by chlorination, or by treatment with ozone (Scheme 9) combined with ultrafiltration. On the other hand, microcystins and nodularins could be modified for example by esterification (Asp and/or Glu residues), transformation of guanidine moiety of arginine, Michael type addition to dehydroamino acids (Dha, Dhb). These modifications provide less toxic compounds, with interesting biological activities.