FORMATION, CHARACTERIZATION, AND TOXICITY OF THE GLUTATHIONE AND CYSTEINE CONJUGATES OF TOXIC HEPTAPEPTIDE MICROCYSTINS

被引:171
作者
KONDO, F [1 ]
IKAI, Y [1 ]
OKA, H [1 ]
OKUMURA, M [1 ]
ISHIKAWA, N [1 ]
HARADA, K [1 ]
MATSUURA, K [1 ]
MURATA, H [1 ]
SUZUKI, M [1 ]
机构
[1] MEIJO UNIV,FAC PHARM,NAGOYA,AICHI 468,JAPAN
关键词
D O I
10.1021/tx00029a002
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Microcystins LR, YR, and RR, cyclic heptapeptide hepatotoxins produced by cyanobacteria, were synthetically converted into glutathione (GSH) and cysteine (Cys) conjugates. Fast atom bombardment mass spectra showed [M + H]+ ions corresponding to GSH and Cys conjugates of microcystins LR, YR, and RR for the obtained compounds. H-1 NMR spectral analyses revealed that two singlet signals of olefinic protons of N-methyldehydroalanine (Mdha) in microcystins disappeared in the conjugates, confirming that thiols of GSH and Cys added nucleophilically to the alpha,beta-unsaturated carbonyl of the Mdha moiety. On examination of the 50% lethal dose (LD50) with intravenous injection using mice, both GSH and Cys conjugates showed reduction in toxicity compared with microcystins, but their toxicity still remained. Microcystin LR and its GSH conjugate were separated and identified in a standard mixture by using a frit-fast atom bombardment liquid chromatography/mass spectrometry (Frit-FAB LC/MS) method. Obtained conjugates in the present study would be important compounds as the standard samples for study of metabolism of microcystins, and the Frit-FAB LC/MS method would be applicable to mass spectrometric identification of metabolites of microcystins.
引用
收藏
页码:591 / 596
页数:6
相关论文
共 42 条
[1]  
[Anonymous], ALGAE MAN ENV
[2]   STRUCTURAL STUDIES ON CYANOGINOSIN-LR, CYANOGINOSIN-YR, CYANOGINOSIN-YA AND -CYANOGINOSIN-YM, PEPTIDE TOXINS FROM MICROCYSTIS-AERUGINOSA [J].
BOTES, DP ;
WESSELS, PL ;
KRUGER, H ;
RUNNEGAR, MTC ;
SANTIKARN, S ;
SMITH, RJ ;
BARNA, JCJ ;
WILLIAMS, DH .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1985, (12) :2747-2748
[3]   THE STRUCTURE OF CYANOGINOSIN-LA, A CYCLIC HEPTAPEPTIDE TOXIN FROM THE CYANOBACTERIUM MICROCYSTIS-AERUGINOSA [J].
BOTES, DP ;
TUINMAN, AA ;
WESSELS, PL ;
VILJOEN, CC ;
KRUGER, H ;
WILLIAMS, DH ;
SANTIKARN, S ;
SMITH, RJ ;
HAMMOND, SJ .
JOURNAL OF THE CHEMICAL SOCIETY-PERKIN TRANSACTIONS 1, 1984, (10) :2311-2318
[4]   ALGAL TOXINS AND WATER-BASED DISEASES [J].
CARMICHAEL, WW ;
JONES, CLA ;
MAHMOOD, NA ;
THEISS, WC .
CRC CRITICAL REVIEWS IN ENVIRONMENTAL CONTROL, 1985, 15 (03) :275-313
[5]   NAMING OF CYCLIC HEPTAPEPTIDE TOXINS OF CYANOBACTERIA (BLUE-GREEN-ALGAE) [J].
CARMICHAEL, WW ;
BEASLEY, V ;
BUNNER, DL ;
ELOFF, JN ;
FALCONER, I ;
GORHAM, P ;
HARADA, KI ;
KRISHNAMURTHY, T ;
YU, MJ ;
MOORE, RE ;
RINEHART, K ;
RUNNEGAR, M ;
SKULBERG, OM ;
WATANABE, M .
TOXICON, 1988, 26 (11) :971-973
[6]  
Chasseaud L.F., 1976, GLUTATHIONE METABOLI, P77
[7]  
COCHRAN WG, 1957, EXPT DESIGNS, P29
[8]   A METHOD FOR OBTAINING AND ANALYZING SENSITIVITY DATA [J].
DIXON, WJ ;
MOOD, AM .
JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION, 1948, 43 (241) :109-126
[9]   HEPATOCYTE DEFORMATION INDUCED BY CYANOBACTERIAL TOXINS REFLECTS INHIBITION OF PROTEIN PHOSPHATASES [J].
ERIKSSON, JE ;
TOIVOLA, D ;
MERILUOTO, JAO ;
KARAKI, H ;
HAN, YG ;
HARTSHORNE, D .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1990, 173 (03) :1347-1353
[10]   LIQUID-CHROMATOGRAPHIC DETERMINATION OF THE CYANOGINOSINS, TOXINS PRODUCED BY THE CYANOBACTERIUM MICROCYSTIS-AERUGINOSA [J].
GATHERCOLE, PS ;
THIEL, PG .
JOURNAL OF CHROMATOGRAPHY, 1987, 408 :435-440