MLR-52, (4'-DEMETHYLAMINO-4',5'-DIHYDROXYSTAUROSPORINE), A NEW INHIBITOR OF PROTEIN-KINASE-C WITH IMMUNOSUPPRESSIVE ACTIVITY

In the course of screening with the mixed lymphocyte reaction, a new i nhibitor of protein kinase C with immunosuppressive activity was isola ted from the fermentation broth and mycelia of Streptomyces sp. AB 186 9R-359. Although certain similarities exist, this strain is morphologi cally and physiologically distinct from other reported producers of st aurosporine-related compounds. We have found that this strain produces relatively high levels of staurosporine and the new minor compound ML R-52, which possesses the indolo[2,3-a]carbazole chromophore of stauro sporine, but differs in the substitution pattern of the sugar moiety. Their structures have been elucidated by mass and NMR spectra. MLR-52 has been shown to inhibit the enzymatic activity of protein kinase C a nd the murine mixed lymphocyte reaction.