INTERACTION OF MARINE TOXIN DOLASTATIN-10 WITH PORCINE BRAIN TUBULIN - COMPETITIVE-INHIBITION OF RHIZOXIN AND PHOMOPSIN A BINDING

Dolastatin 10, a cytostatic peptide containing several unique amino ac id subunits, was isolated from the marine shell-less mollusk Dolabella auricularia. It inhibits microtubule assembly at concentrations below 5.0 mu M (IC50, 3.0 mu M) and causes formation of tubulin aggregates at higher (>10 mu M) concentrations in a somewhat different manner fro m that caused by vinblastine. Electron microscopical analysis showed i rregular aggregates of microtubule proteins in the presence of 10 mu M dolastatin 10. Dolastatin 10 inhibited the binding of both radiolabel ed rhizoxin and phomopsin A to tubulin with inhibition constants (K-i) of 7 x 10(-8) M and 1 x 10(-7) M, respectively. The results suggest t hat at least one of the binding sites of dolastatin 10 on tubulin is t he rhizoxin binding site.