Studies on the Cu(II) and Zn(II) binding properties of cyclic peptides from the ascidian Lissoclinum patella
Three modified cyclic peptides were isolated from a sample of the ascidian Lissoclinum patella by solvent extraction methods and their structures elucidated using NMR and MS. The major compound was identified as petallamide C and the two minor compounds as new members of the lissoclinamide family of peptides. They were named lissoclinamide 9 and lissoclinamide 10. The metal binding properties of the three cyclic peptides were then studied by circular dichroism (CD ) and by MS. All three were found to bind copper and zinc, and binding constants for these were calculated from CD titrations and from MS monitored titrations. Competition experiments showed that both patellamide C and lissoclinamide 10 selectively bound copper in the presence of zinc. No selectivity was shown by lissoclinamide 9. None of the compounds were found to bind any other metals. Patellamide C was found to alter conformation on binding to copper. It's binding properties were compared to those of petellamide A, a related compound from Lissoclinum patella. Solution conformations of patellamide C and lissoclinamide 9 were generated computationally using nOe restrained modelling. The solution conformations of zinc bound and of copper bound patellamide C were also produced by this method. Binding sites for copper within the patellamides and the lissoclinamides were proposed.