BINDING OF BREVETOXINS AND CIGUATOXIN TO THE VOLTAGE-SENSITIVE SODIUM-CHANNEL AND CONFORMATIONAL-ANALYSIS OF BREVETOXIN-B

被引:59
作者
GAWLEY, RE [1 ]
REIN, KS [1 ]
KINOSHITA, M [1 ]
BADEN, DG [1 ]
机构
[1] UNIV MIAMI,ROSENSTIEL SCH MARINE & ATMOSPHER SCI,NIEHS,CORAL GABLES,FL 33124
关键词
D O I
10.1016/0041-0101(92)90014-V
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The marine toxins known generically as brevetoxins, as well as their structural relative ciguatoxin, are known as polyether ladder toxins, and bind uniquely to site 5 of the voltage-sensitive sodium channel. Rat brain synaptosome binding data show similarities in binding affinity for brevetoxins having the same structural (ladder) backbone, but different affinities between brevetoxins having different backbones. Ciguatoxin has a different backbone from the brevetoxins, but binds even more strongly to the same site. Could the flexibility of the backbone be related to their relative toxicities? As part of an effort to identify the common pharmacophore for the toxins, Monte Carlo methods were used to generate conformational models of the polyether ladder toxin brevetoxin B (PbTx-2) which shows significant flexibility at the juncture of the two 7-membered rings.
引用
收藏
页码:780 / 785
页数:6
相关论文
共 30 条
  • [11] EDWARDS RA, 1992, IN PRESS MOL BRAIN R
  • [12] EFFECTS OF CRUDE BREVETOXIN ON MEMBRANE-POTENTIAL AND SPONTANEOUS OR EVOKED ENDPLATE POTENTIALS IN RAT HEMIDIAPHRAGM
    GALLAGHER, JP
    SHINNICKGALLAGHER, P
    [J]. TOXICON, 1985, 23 (03) : 489 - 496
  • [13] HUANG JMC, 1984, J PHARMACOL EXP THER, V229, P615
  • [14] BIOSYNTHETIC ORIGINS AND ASSIGNMENTS OF C-13 NMR PEAKS OF BREVETOXIN-B
    LEE, MS
    REPETA, DJ
    NAKANISHI, K
    ZAGORSKI, MG
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1986, 108 (24) : 7855 - 7856
  • [15] BIOSYNTHETIC-STUDIES OF BREVETOXINS, POTENT NEUROTOXINS PRODUCED BY THE DINOFLAGELLATE GYMNODINIUM-BREVE
    LEE, MS
    QIN, GW
    NAKANISHI, K
    ZAGORSKI, MG
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (16) : 6234 - 6241
  • [16] ISOLATION AND STRUCTURE OF BREVETOXIN-B FROM THE RED TIDE DINOFLAGELLATE PTYCHODISCUS-BREVIS (GYMNODINIUM, BREVE)
    LIN, YY
    RISK, M
    RAY, SM
    VANENGEN, D
    CLARDY, J
    GOLIK, J
    JAMES, JC
    NAKANISHI, K
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1981, 103 (22) : 6773 - 6775
  • [17] ENANTIOMERIC SYNTHESIS OF ENDO-SUBSTITUTED TETRAHYDROPYRANS
    MARTIN, VS
    NUNEZ, MT
    RAMIREZ, MA
    SOLER, MA
    [J]. TETRAHEDRON LETTERS, 1990, 31 (05) : 763 - 766
  • [18] MACROMODEL - AN INTEGRATED SOFTWARE SYSTEM FOR MODELING ORGANIC AND BIOORGANIC MOLECULES USING MOLECULAR MECHANICS
    MOHAMADI, F
    RICHARDS, NGJ
    GUIDA, WC
    LISKAMP, R
    LIPTON, M
    CAUFIELD, C
    CHANG, G
    HENDRICKSON, T
    STILL, WC
    [J]. JOURNAL OF COMPUTATIONAL CHEMISTRY, 1990, 11 (04) : 440 - 467
  • [19] STRUCTURES OF CIGUATOXIN AND ITS CONGENER
    MURATA, M
    LEGRAND, AM
    ISHIBASHI, Y
    YASUMOTO, T
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1989, 111 (24) : 8929 - 8931
  • [20] SYNTHESIS OF MEDIUM-SIZED RING ETHERS FROM THIONOLACTONES - APPLICATIONS TO POLYETHER SYNTHESIS
    NICOLAOU, KC
    MCGARRY, DG
    SOMERS, PK
    KIM, BH
    OGILVIE, WW
    YIANNIKOUROS, G
    PRASAD, CVC
    VEALE, CA
    HARK, RR
    [J]. JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1990, 112 (17) : 6263 - 6276