PURIFICATION AND CHARACTERIZATION OF ASEANOSTATINS - ACTINOMYCETE-DERIVED FATTY-ACID INHIBITORS TO MYELOPEROXIDASE RELEASE FROM HUMAN POLYMORPHONUCLEAR LEUKOCYTES

被引:9
作者
ISHIDAOKAWARA, A
KIMOTO, Y
WATANABE, K
TOKUDA, K
SHIBATA, M
MASUDA, K
TAKANO, Y
KAWAGUCHI, K
AKAGAWA, H
NILUBOL, N
HOTTA, K
YAZAWA, K
MIZUNO, S
SUZUKI, K
机构
[1] NATL INST HLTH,DEPT ANTIBIOT,2-10-35 KAMIOSAKI,SHINAGAWA KU,TOKYO 141,JAPAN
[2] SAGAMI CHEM RES CTR,SAGAMIHARA,KANAGAWA 229,JAPAN
[3] TOKYO METROPOLITAN UNIV,FAC SCI,DEPT BIOL,SETAGAYA KU,TOKYO 158,JAPAN
[4] CHULALONGKORN UNIV,INST BIOTECHNOL & GENET ENGN,BANGKOK 10500,THAILAND
关键词
D O I
10.7164/antibiotics.44.524
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
We found inhibitors, designated aseanostatins P1 and P5, against myeloperoxidase (MPO) release from human polymorphonuclear leukocytes (PMN). Aseanostatins were extracted from an actinomycete isolated in Thailand and purified by a series of column chromatography of charcoal and silica gel, and HPLC. Physico-chemical characterization by gas liquid chromatography and GC-MS indicated that aseanostatins were fatty acids. The active forms of aseanostatins were recovered by hydrolyzing their methyl esters after HPLC. Two components P1 and P5 with the IC50 of 0.96 and 0.54-mu-g/ml to the MPO release were obtained as pure forms, indicating aseanostatin P5 was higher activity than aseanostatin P1. The component P1 was identical with 12-methyltridecanoic acid and P5 was indistinguishable to 12-methyltetradecanoic acid (ante-i-15:0). Aseanostatin P5 (1-mu-g/ml) did not inhibit beta-glucuronidase release, but O2- production a little. It has no effect on chemotaxis of PMN to fMet-Leu-Phe (10(-8)M), PMN adhesion or phosphorylation of a 64-kD protein in the PMN cell-lysate system.
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页码:524 / 532
页数:9
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