ABSTRACT
K-259-2, a new inhibitor of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase, was isolated from the cultured broth of Micromonospora olivasterospora K-259. K-259-2 has an anthraquinone moiety in its structure. IC50 values for the effect of K-259-2 against Ca2+ and calmodulin-stimulated activity of the enzyme preparations from bovine brain and heart were 6.6 and 2.9 microM, respectively. On the other hand, basal activity (the activity in the presence of ethylene bis(oxyethylenenitrilo)tetraacetic acid (EGTA) instead of Ca2+/calmodulin) of the bovine brain enzyme, calmodulin-independent cyclic nucleotide phosphodiesterase from bovine heart, and protein kinase C from rat brain were inhibited by K-259-2 to a lesser extent with IC50 values of 27.4, 40.7 and 45.8 microM, respectively.
Subject(s)
Anthraquinones/biosynthesis , Calmodulin/antagonists & inhibitors , Micromonospora/classification , Phosphodiesterase Inhibitors/biosynthesis , Anthraquinones/isolation & purification , Anthraquinones/pharmacology , Chemical Phenomena , Chemistry, Physical , Fermentation , Micromonospora/metabolism , Soil MicrobiologyABSTRACT
KS-619-1, a new inhibitor of Ca2+ and calmodulin-dependent cyclic nucleotide phosphodiesterase, was isolated from the cultured broth of Streptomyces californicus. KS-619-1 has an anthraquinone moiety. IC50 values for the effect of KS-619-1 on Ca2+ and calmodulin-stimulated activity of bovine brain and heart enzymes were 2.0 and 1.5 microM, respectively. On the other hand, basal activity (the activity in the presence of ethylene bis(oxyethylenenitrilo)tetraacetic acid (EGTA) instead of Ca2+/calmodulin) of the bovine brain enzyme, calmodulin-independent cyclic nucleotide phosphodiesterase from bovine heart, and protein kinase C from rat brain were inhibited by KS-619-1 to a lesser extent with IC50 values; 12.3, 25.9 and 151 microM, respectively.
