1. MLR-52, (4'-demethylamino-4',5'-dihydroxystaurosporine), a new inhibitor of protein kinase C with immunosuppressive activity.
- Author
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McAlpine JB, Karwowski JP, Jackson M, Mullally MM, Hochlowski JE, Premachandran U, and Burres NS
- Subjects
- Animals, Culture Media, Female, Fermentation, In Vitro Techniques, Lymphocyte Culture Test, Mixed, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Staurosporine analogs & derivatives, Streptomyces metabolism, Alkaloids chemistry, Alkaloids isolation & purification, Alkaloids metabolism, Alkaloids pharmacology, Immunosuppressive Agents chemistry, Immunosuppressive Agents isolation & purification, Protein Kinase C antagonists & inhibitors
- Abstract
In the course of screening with the mixed lymphocyte reaction, a new inhibitor of protein kinase C with immunosuppressive activity was isolated from the fermentation broth and mycelia of Streptomyces sp. AB 1869R-359. Although certain similarities exist, this strain is morphologically and physiologically distinct from other reported producers of staurosporine-related compounds. We have found that this strain produces relatively high levels of staurosporine and the new minor compound MLR-52, which possesses the indolo[2,3-a]carbazole chromophore of staurosporine, 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 and the murine mixed lymphocyte reaction.
- Published
- 1994
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