Scytonemin A, a Novel Calcium Antagonist from a Blue-Green Alga

A novel cyclic peptide, scytonemin A, possessing potent calcium antagonistic properties is a major metabolite of the cultured cyanophyte Scytonema sp. (strain U-3-3). Vigorous acid hydrolysis of scytonemin A leads to L-alanine, 2 equiv of glycine, L-homoserine (Hse), D-(2R,3S)-threo-3-hydroxyleucine (HyLeu), D-leucine, D-serine, L-(2S,3S)-trans-3-methylproline (MePro), 2 equiv of L-(2S,3R,4R)-4-hydroxy-3-methylproline (HyMePro), D-phenylalanine, and (2S,3R,5S)-3-amino-2,5,9-trihydroxy-10-phenyldecanoic acid (Ahda). Mild acid hydrolysis results in predominantly two acyclic peptides, viz. Ser-Gly-HyMePro-HyMePro-Leu-Hse and Phe-Gly-HyLeu- MePro-Ahda. Still milder hydrolysis results in selective cleavage of the homoseryl amide bond in scytonemin A to give an acyclic peptide, Phe-Gly-HyLeu-MePro-Ahda-Ser-Gly-HyMePro-HyMePro-Leu-Hse, with an N-acetylalanyl unit attached via an ester linkage to C-5 of Ahda and a homoseryl lactone unit at the carboxyl terminus. State-of-the-art NMR and MS techniques have been used to determine the total structures of scytonemin A and the degradation products.