WF-3161

The sequence and configuration of amino acids in the cytostatic cyclic tetrapeptide WF-3161 are established as cyclo(L-Leu-L-Pip-L-Aoe-D-Phe) where Pip = pipecolic acid and Aoe = 2-amino-8-oxo-9,10-epoxydecanoic acid. In chloroform, WF-3161 adopts a conformation with a possible gamma-turn between Leu NH and Aoe C = O and a cis amide bond between Leu and Pip. The torsion angles for this conformation are L-Aoe, phi, -95 degrees, psi, +85 degrees, omega, -155 degrees; D-Phe, phi, +120 degrees, psi, -80 degrees, omega, -175 degrees; L-Leu, phi, -145 degrees, psi, +35 degrees, omega, -10 degrees; L-Pip, phi, +20 degrees, psi, -135 degrees, omega, -170 degrees. The cis,trans,trans,trans amide bond sequence is related to the dimethyl sulfoxide conformation of chlamydocin, another cytostatic cyclic tetrapeptide.

WF-3161 is an antitumor antibiotic produced by a strain of fungus, Petriella guttulata. The antibiotic was purified by solvent extraction and a combination of silica gel and reverse phase column chromatography. The chemical structure of the antibiotic (C31H44N4O6, mp 181-183 degrees C) was found to be a cyclic tetrapeptide consisting of phenylalanine, leucine, pipecolinic acid and 2-amino-8-oxo-9,10-epoxydecanoic acid. WF-3161 inhibited the growth of Trichophyton asteroides. It prolonged survival period of mice bearing leukemia P-388 with a high therapeutic index.