SOLUTION CONFORMATIONS OF PATELLAMIDE-B AND PATELLAMIDE-C, CYTOTOXIC CYCLIC HEXAPEPTIDES FROM MARINE TUNICATE, DETERMINED BY NMR-SPECTROSCOPY AND MOLECULAR-DYNAMICS

In order to elucidate a possible relationship between the chemical structure and molecular conformation/stability of cytotoxic cyclic hexapeptides from a marine tunicate, Lissoclinum patella, the solution conformations of patellamides B and C, the chemical structures of which deviate from the C-2-symmetry at two positions, were analyzed by means of H-1-NMR spectroscopy and restrained molecular dynamics simulation. The two molecules took similar twisted ''figure eight-like'' backbone conformations without intramolecular hydrogen bonding (type III) in chloroform solution. The outline of these cyclic backbone conformations is similar to that of a related non-C-2-symmetric patellamide D observed in the crystal structure, but deviates significantly from the ''square form'' (type I) of the C-2-symmetric ascidiacyclamide or the slightly structurally deformed patellamide A. Results indicate that preference for the type I or III conformation is dependent on the degree of asymmetry of the side chains attached to the two halves of the C-2-symmetric backbone structure. The possible conformation of the cytotoxic cyclic hexapeptide is discussed in relation to its biological activity.