Isolation and structure of the marine sponge cell growth inhibitory cyclic peptide phakellistatin 1

A new cell growth inhibitory (P-388 murine leukemia ED50 7.5 micrograms/ml) cycloheptapeptide designated phakellistatin 1 was isolated from two Indo-Pacific sponges, Phakellia costata and Stylotella aurantium. Structural elucidation was accomplished utilizing high field nmr, amino acid analyses, and mass spectral techniques (fab, tandem ms/ms), followed by chiral gas chromatographic procedures for absolute configuration assignments (all S-amino acid units). By these methods phakellistatin 1 [1] was found to be cyclo (Pro-Ile-Pro-Ile-Phe-Pro-Tyr), and this assignment was finally confirmed by an X-ray crystal structure determination.