M Namikoshi — Page 3 | PubMed Health

PubMedDate not supplied

Structures of three new homotyrosine-containing microcystins and a new homophenylalanine variant from Anabaena sp. strain 66.

A hepatotoxic strain of cyanobacterium Anabaena sp. 66 was isolated from a hepatotoxic water bloom sample in Lake Kiikkara, Finland. Four cyclic heptapeptide hepatotoxins were isolated and purified by HPLC from cultured cells of this organism. The structures of three new homotyrosine (Hty) containing toxins, [Dha7]microcystin-HtyR (Dha = dehydroalanine) (1), [D-Asp3,Dha7]microcystin-HtyR (2), and [L-Ser7]microcystin-HtyR (3), were assigned, based upon amino acid analyses using both a Waters Pico Tag HPLC system and chiral capillary GC, 1H NMR, fast atom bombardment mass spectrometry (FABMS), and collisionally induced tandem FABMS. A new homophenylalanine (Hph) variant of 1, [Dha7]microcystin-HphR (4), was also obtained as a minor component. Compound 3 is most likely a biosynthetic precursor of 1. The four new toxins did not have an N-methyl group at the dehydroamino acid or its precursor unit.

Amino Acid Sequence↗

PubMedDate not supplied

Chemical characterization and toxicity of dihydro derivatives of nodularin and microcystin-LR, potent cyanobacterial cyclic peptide hepatotoxins.

Dihydro derivatives of nodularin (1) and microcystin-LR (4), potent cyclic peptide hepatotoxins isolated from Nodularia spumigena and Microcystis aeruginosa, respectively, were prepared by sodium borohydride reduction of the dehydroamino acid residues. The two stereoisomers of both dihydronodularin (2 and 3) and dihydromicrocystin-LR (5 and 6), isolated by reversed-phase HPLC, showed similar toxicity to each other [ip in mice, LD50 = 150 (2), 150 (3), 85 (5), and 100 (6) micrograms/kg]. The stereochemistries of the reduced amino acids obtained by acid hydrolysis of dihydronodularin and dihydromicrocystin-LR [respectively, alpha-(methylamino)butyric acid and N-methylalanine] were determined by GC on a permethylated beta-cyclodextrin capillary column as their trifluoroacetyl methyl ester derivatives. Authentic L- and DL-N-methylamino acids were prepared to compare directly with the natural amino acids. Deuterated derivatives were also prepared using sodium borodeuteride (98 atom % D), and the location (beta) and percentage (78-84%) of the deuterium incorporation were determined.

Animals↗