MS-282A AND MS-282B, NEW INHIBITORS OF CALMODULIN-ACTIVATED MYOSIN LIGHT-CHAIN KINASE FROM STREPTOMYCES-TAURICUS ATCC-27470

MS-282a and MS-282b were isolated from the culture broth of Streptomyc es tala icus ATCC 27470 as inhibitors of smooth muscle myosin light ch ain kinase (MLCK). MS-282a and MS-282b inhibited the activity of chick en gizzard MLCK with IC50 values of 3.8 mu M and 5.2 mu M, respectivel y. Cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein k inase and protein kinase C were not inhibited by 150 mu M MS-282a at a ll. It is likely that MS-282a blocks MLCK activity by antagonizing cal modulin since 1) the compound inhibited calmodulin-dependent but not c almodulin-independent activity of MLCK; 2) the inhibition of MLCK was antagonized by increasing concentrations of calmodulin, and 3) the com pound inhibited calmodulin-dependent cyclic nucleotide phosphodiestera se.