Patellamides Cytotoxic Cyclic Peptides

Ascidians are marine filter feeders with a rich natural products chemistry that five commonly associated with symbiotic bacteria (88, 89, 109). A well-studied symbiosis consists of photosynthetic Prochloron spp. cyanobacteria that occur in ascidians of the family Didemnidae (110). Prochloron spp. also can be found in bacterial mat structures of stromatoliths (111) but so far have not been detected outside of such structured environments. From didemnid ascidians, numerous cytotoxic cyclic peptides of the patellamide group (Fig. 5) were isolated (109, 112, 113). Mechanical separation of the Prochloron sp. symbiont from its host Lissoclinum patella and subsequent genome sequencing revealed a set of biosynthetic genes that after transfer into E. coli enabled this bacterium to produce two different patellamides (114). The genes also were identified in an independent study by screening a library of Prochloron sp. DNA... 

Patellamides B and C, Cytotoxic Cyclic Peptides from a Tunicate. 2. Their Real Structures have been Determined by Their Syntheses. Tetrahedron Lett. 26, 5159 (1985). 

In, Y, Doi, M., Inoue, M., Ishida, T., Hamada, Y, and Shioiri, T. (1994a) Patellamide A, a cytotoxic cyclic peptide from the ascidian Lissoclinum patella. Acta Crystcdlgr. Sect. C, 50, 432-434. 

The cyclamides are small cyclic peptides that characteristically contain multiple thiazole, thiazoline, oxazole, and oxazoline rings, which are derived from cysteine, serine, and threonine residues. Some of the first examples of this class to be described were the patellamides (53-55) from the tunicate Lissoclinum patella, although it was later determined they were produced by the symbiotic cyanobacterium Prochloron sp. The structures were solved by a combination of acid hydrolysis and GC analysis, coupled with 2D NMR. Smaller cyclic peptides from this class include the hexapeptides westiellamide (56) and microcyclamide (57) from M. aeruginosa Many members of the class possess cytotoxic properties, although their biological function or mechanism of action is not fully understood. In contrast to many cyanobacterial peptides, aside from the unusual heterocyclic residues, these peptides generally contain only ribosomal amino acids. 

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