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 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.
McAlpine
J B
JB
Pharmaceutical Products Research and Development Abbott Laboratories, Abbott Park, Illinois 60064.
Karwowski
J P
JP
Jackson
M
M
Mullally
M M
MM
Hochlowski
J E
JE
Premachandran
U
U
Burres
N S
NS
D000470:Alkaloids / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D003470:Culture Media; D005260:Female; D005285:Fermentation; D007166:Immunosuppressive Agents / Q000737:chemistry / Q000302:isolation & purification; D066298:In Vitro Techniques; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D019311:Staurosporine / Q000031:analogs & derivatives; D013302:Streptomyces / Q000378:metabolism
D000470:Alkaloids; D003470:Culture Media; D007166:Immunosuppressive Agents; C087121:4'-demethylamino-4',5'-dihydroxystaurosporine; D011493:Protein Kinase C; D019311:Staurosporine