ISOLATION OF LINEAR PEPTIDES RELATED TO THE HEPATOTOXINS NODULARIN AND MICROCYSTINS

Linear peptide 2, Adda-D-Glu(gamma)-Mdhb-D-MeAsp(beta)-L-Arg-OH, was i solated from cultured Nodularia spumigena and was analyzed in the cell s after one week's (1:2 : 30:1) to eight week's (>100:1) cultivation. Three linear peptides, Glu(gamma)-Mdha-D-Ala-L-Leu-D-MeAsp(beta)-L-Arg -OH (3), -MeAsp(beta)-L-Arg-Adda-D-Glu(gamma)-Mdha-D-Ala-OH (4), and - MeAsp(beta)-L-Arg-Adda-D-Glu(gamma)-Mdha-D-Ala-OH (5) were obtained fr om a water bloom of Microcystis spp. collected from Homer Lake (Illino is). Some of these linear peptides (2, 3) are thought to be biogenetic precursors of nodularin and microcystins. Linear peptides 2, 3, and 4 did not show apparent toxicity at 1.0, 1.1, and 2.25 mg/kg, respectiv ely, in a mouse bioassay tip). Feeding experiments using C-13-labeled precursors established that the 2-, 6- and 8-methyl and 9-methoxy carb ons of the unusual -methoxy-2,6,8-trimethyl-10-phenyl-4,6-decadienoic acid (Adda) unit of 1 were clearly derived from L-methionine.