New synthesis and biological activity of the cyclic tetrapeptides tentoxin and [Pro 1] tentoxin

The cyclic tetrapeptide tentoxin and the conformationally related analog [Pro1] tentoxin have been synthesized by a new solution methodology. D, L-3-phenyl-serine was employed as a synthetic precursor to the Z-dehydrophenylalanine substituent. Increased yields of both compounds were obtained when a modified cyclization procedure was employed through ring closure from the N-terminal substituents of N-methylalanine and proline to a C-terminal glycine. Biological activities were determined in a seedling assay used to measure chlorosis induction. Both tentoxin and [Pro1] tentoxin exhibited similar chlorosis inducing activity. Whole leaf extracts of chlorotic, [Pro1] tentoxin-treated seedling leaves lacked active polyphenoloxidase when subjected to electrophoretic analysis. Coupling factor1 (CF1) ATPase isozymes were assayed for ATPase activity in 10μuM-100 μuM solutions of tentoxin and [Pro1] tentoxin. CF1 ATPase inhibition was observed for both tentoxin and [Pro1] tentoxin. Inhibition of a single ATPase isozyme by tentoxin was alleviated at or above 50μuM while [Pro1] tentoxin inhibited two CF1 ATPases at concentrations up to 110μuM. No alleviation of ATPase inhibition was noted for higher concentrations of [Pro1] tentoxin.