Strepogenin Activity of Seryl Glycyl Glutamic Acid

Since Plattner and Clauson-Kaas* have isolated the tomato-wilting agent elaborated by the pathogenic fungus Fusarium lycopersici, and have shown it to be a peptide containing aspartic acid, the idea occurred to the author that this toxic substance might be an inhibitory structural analogue of strepogenin.2s3 This working hypothesis arose because considerable evidence had been found in this laboratory to show that strepogenin is a peptide of glutamic acid.The arguments for this cannot be expanded at this time, except to say that strepogenin concentrates are rich in glutamic aeid, and that, for Lactobacillus cusei, derivatives of glutamic acid such as glutamine and glutathione have activity.However, these y-amides of glutamic acid are destroyed by heat, whereas strepogenin is not.With,either crude or pure preparations of the tomato-wilting Fusarium substance (lycomarasmin),4 it has been possible to show that the biological effects of the toxin are negated by concentrates of strepogenin.Thus the wilting action on tomato leaves and also the inhibition of growth of L. casei caused by lycomarasmin were reversed by strepogenin preparations.. The antagonism was competitive, at least over a limited range of concentrations.The elucidation of the structure of lycomarasmin therefore becomes of prime importance, because if this were known, the const.itution of strepogenin might be deduced from it.Plattner and Clauson-Kaas" found that hydrolysis of lycomarasmin, CeHla07K3, yielded aspartic acid, glycine, and pyruvic acid, and proposed a structure for it.4Becau&e certain serine peptides are known to yield pyruvic acid on acid hydrolysis, it seemed possible that lycomarasmin might really contain serine.Accordingly, seryl glycyl aspartic acid and glycyl seryl aspartic acid were synthesized and found to possess tomato leaf-wilting activity.The first was about one-sixth, and the second was one-half to one-fourth as active as lycomarasmin.Despite this activity it is uncertain whether either of these peptidcs is identical with lycomarasmin because they were less potent and more water-soluble.These differences, however, may have resided in the fact that the serine was dl.Nevertheless, seryl glycyl glutamic acid was synthesized and tested for strepogenin activity.The synthesis was accomplished by the following