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

被引:15
作者
NAKANISHI, S [1 ]
KITA, K [1 ]
UOSAKI, Y [1 ]
YOSHIDA, M [1 ]
SAITOH, Y [1 ]
MIHARA, A [1 ]
KAWAMOTO, I [1 ]
MATSUDA, Y [1 ]
机构
[1] KYOWA HAKKO KOGYO CO LTD,PHARMACEUT RES LABS,NAGAIZUMI,SHIZUOKA 411,JAPAN
关键词
D O I
10.7164/antibiotics.47.855
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
MS-282a and MS-282b were isolated from the culture broth of Streptomyces tala icus ATCC 27470 as inhibitors of smooth muscle myosin light chain kinase (MLCK). MS-282a and MS-282b inhibited the activity of chicken gizzard MLCK with IC50 values of 3.8 mu M and 5.2 mu M, respectively. Cyclic AMP-dependent protein kinase, cyclic GMP-dependent protein kinase and protein kinase C were not inhibited by 150 mu M MS-282a at all. It is likely that MS-282a blocks MLCK activity by antagonizing calmodulin since 1) the compound inhibited calmodulin-dependent but not calmodulin-independent activity of MLCK; 2) the inhibition of MLCK was antagonized by increasing concentrations of calmodulin, and 3) the compound inhibited calmodulin-dependent cyclic nucleotide phosphodiesterase.
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页码:855 / 861
页数:7
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