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 \u751f\u5316\u5b66\u3084\u85ac\u7406\u5b66\u3067\u306f\u3001\u30ea\u30ac\u30f3\u30c9(Ligand; \u30e9\u30a4\u30ac\u30f3\u30c9)\u3068\u306f\u751f\u4f53\u5206\u5b50\u3068\u8907\u5408\u4f53\u3092\u5f62\u6210\u3057\u3066\u751f\u7269\u5b66\u7684\u306a\u76ee\u7684\u3092\u679c\u305f\u3059\u7269\u8cea\u306e\u3053\u3068\u3092\u6307\u3059\u3002 \u30bf\u30f3\u30d1\u30af\u8cea-\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u3067\u306f\u3001\u30ea\u30ac\u30f3\u30c9\u306f\u901a\u5e38\u3001\u6a19\u7684\u30bf\u30f3\u30d1\u30af\u8cea\u4e0a\u306e\u7d50\u5408\u90e8\u4f4d\u306b\u7d50\u5408\u3059\u308b\u3053\u3068\u3067\u30b7\u30b0\u30ca\u30eb\u3092\u751f\u6210\u3059\u308b\u5206\u5b50\u3067\u3042\u308b\u3002 \u3053\u306e\u7d50\u5408\u306f\u3001\u901a\u5e38\u3001\u6a19\u7684\u30bf\u30f3\u30d1\u30af\u8cea\u306e\u914d\u5ea7\u7570\u6027\u4f53(\u30b3\u30f3\u30d5\u30a9\u30e1\u30fc\u30b7\u30e7\u30f3)\u306e\u5909\u5316\u3092\u3082\u305f\u3089\u3059\u3002 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\u306b\u7531\u6765\u3057\u3066\u3044\u308b\u3002\u53d7\u5bb9\u4f53\u30bf\u30f3\u30d1\u30af\u8cea\u306b\u7d50\u5408\u3057\u305f\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u4e09\u6b21\u5143\u5f62\u72b6\u306e\u914d\u5411\u6027\u306b\u5f71\u97ff\u3092\u4e0e\u3048\u3066\u7acb\u4f53\u914d\u5ea7(\u30b3\u30f3\u30d5\u30a9\u30e1\u30fc\u30b7\u30e7\u30f3)\u3092\u5909\u5316\u3055\u305b\u308b\u3002 \u53d7\u5bb9\u4f53\u30bf\u30f3\u30d1\u30af\u8cea\u306e\u30b3\u30f3\u30d5\u30a9\u30e1\u30fc\u30b7\u30e7\u30f3\u306f\u6a5f\u80fd\u72b6\u614b\u3092\u69cb\u6210\u3057\u3066\u3044\u308b\u3002 \u30ea\u30ac\u30f3\u30c9\u306b\u306f\u3001\u57fa\u8cea\u3001\u963b\u5bb3\u5264\u3001\u6d3b\u6027\u5316\u5264\uff08\u82f1\u8a9e\u7248\uff09\u3001\u8102\u8cea\u4f9d\u5b58\u6027\u30a4\u30aa\u30f3\u30c1\u30e3\u30cd\u30eb(signaling lipids)\u3001\u795e\u7d4c\u4f1d\u9054\u7269\u8cea\u306a\u3069\u304c\u3042\u308b\u3002 \u7d50\u5408\u7387\u306f\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u89aa\u548c\u6027\u3068\u547c\u3070\u308c\u3001\u3053\u306e\u6e2c\u5b9a\u306f\u52b9\u679c\u306e\u50be\u5411\u3084\u5f37\u3055\u3092\u4ee3\u8868\u3059\u308b\u3082\u306e\u3067\u3042\u308b\u3002 \u7d50\u5408\u89aa\u548c\u6027\u306f\u3001\u30db\u30b9\u30c8-\u30b2\u30b9\u30c8\u76f8\u4e92\u4f5c\u7528\uff08\u82f1\u8a9e\u7248\uff09\u3060\u3051\u3067\u306a\u304f\u3001\u6eb6\u6db2\u4e2d\u3067\u975e\u5171\u6709\u7d50\u5408\u3092\u99c6\u52d5\u3059\u308b\u652f\u914d\u7684\u3067\u7acb\u4f53\u52b9\u679c\u7684\u306a\u5f79\u5272\u3092\u679c\u305f\u3059\u3053\u3068\u304c\u3067\u304d\u308b\u6eb6\u5a92\u306e\u52b9\u679c\u306b\u3088\u3063\u3066\u3082\u5b9f\u73fe\u3055\u308c\u308b[3]\u3002 \u6eb6\u5a92\u306f\u3001\u30ea\u30ac\u30f3\u30c9\u3068\u53d7\u5bb9\u4f53\u304c\u9069\u5fdc\u3059\u308b\u305f\u3081\u306e\u5316\u5b66\u7684\u74b0\u5883\u3092\u63d0\u4f9b\u3057\u3001\u305d\u306e\u7d50\u679c\u3001\u30d1\u30fc\u30c8\u30ca\u30fc\u3068\u3057\u3066\u304a\u4e92\u3044\u3092\u53d7\u3051\u5165\u308c\u305f\u308a\u62d2\u5426\u3057\u305f\u308a\u3059\u308b\u3002\u653e\u5c04\u6027\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u653e\u5c04\u6027\u540c\u4f4d\u4f53\u6a19\u8b58\u5316\u5408\u7269\u3067\u3042\u308a\u3001PET\u7814\u7a76\u306e\u30c8\u30ec\u30fc\u30b5\u30fc\u3068\u3057\u3066\u3001\u307e\u305fin vitro\u3067\u306e\u7d50\u5408\u7814\u7a76\u306e\u305f\u3081\u306b\u751f\u4f53\u5185(in vivo)\u3067\u4f7f\u7528\u3055\u308c\u3066\u3044\u308b\u3002  \u7279\u306b\u30bf\u30f3\u30d1\u30af\u8cea\u3068\u7279\u7570\u7684\u306b\u7d50\u5408\u3059\u308b\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u5fae\u91cf\u3067\u3042\u3063\u3066\u3082\u751f\u4f53\u306b\u5bfe\u3057\u3066\u975e\u5e38\u306b\u5927\u304d\u306a\u5f71\u97ff\u3092\u4e0e\u3048\u308b\u3002\u305d\u306e\u305f\u3081\u85ac\u5b66\u3084\u5206\u5b50\u751f\u7269\u5b66\u306e\u5206\u91ce\u3067\u306f\u91cd\u8981\u306a\u7814\u7a76\u5bfe\u8c61\u306b\u306a\u3063\u3066\u3044\u308b\u3002Table of Contents\u53d7\u5bb9\u4f53\u7d50\u5408\u89aa\u548c\u6027\/\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u89aa\u548c\u6027[\u7de8\u96c6]\u85ac\u52b9\u3068\u7d50\u5408\u89aa\u548c\u6027[\u7de8\u96c6]\u9078\u629e\u7684\u3068\u975e\u9078\u629e\u7684[\u7de8\u96c6]\u758e\u6c34\u6027\u30ea\u30ac\u30f3\u30c9[\u7de8\u96c6]\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9[\u7de8\u96c6]\u30e2\u30ce\u304a\u3088\u3073\u30dd\u30ea\u30c7\u30ba\u30df\u30c3\u30af\u30fb\u30ea\u30ac\u30f3\u30c9[\u7de8\u96c6]\u7279\u6a29\u7684\u8db3\u5834[\u7de8\u96c6]\u7d50\u5408\u6027\u3092\u8abf\u3079\u308b\u305f\u3081\u306b\u7528\u3044\u3089\u308c\u308b\u65b9\u6cd5[\u7de8\u96c6]\u95a2\u9023\u9805\u76ee[\u7de8\u96c6]\u53d7\u5bb9\u4f53\u7d50\u5408\u89aa\u548c\u6027\/\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u89aa\u548c\u6027[\u7de8\u96c6]\u30ea\u30ac\u30f3\u30c9\u3068\u305d\u306e\u7d50\u5408\u90e8\u4f4d\u3068\u306e\u76f8\u4e92\u4f5c\u7528\u306f\u3001\u7d50\u5408\u89aa\u548c\u6027\u306e\u89b3\u70b9\u304b\u3089\u7279\u5fb4\u4ed8\u3051\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u3002 \u4e00\u822c\u7684\u306b\u3001\u9ad8\u89aa\u548c\u6027\u306e\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u306f\u3001\u30ea\u30ac\u30f3\u30c9\u3068\u305d\u306e\u53d7\u5bb9\u4f53\u306e\u9593\u306e\u3088\u308a\u5927\u304d\u306a\u5438\u5f15\u529b\u306b\u3088\u308b\u3082\u306e\u3067\u3042\u308b\u304c\u3001\u4f4e\u89aa\u548c\u6027\u306e\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u306f\u5438\u5f15\u529b\u304c\u5c11\u306a\u3044\u3002 \u4e00\u822c\u7684\u306b\u3001\u9ad8\u89aa\u548c\u6027\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u306f\u3001\u4f4e\u89aa\u548c\u6027\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u306e\u5834\u5408\u3088\u308a\u3082\u30ea\u30ac\u30f3\u30c9\u306b\u3088\u308b\u53d7\u5bb9\u4f53\u306e\u5360\u6709\u7387\u304c\u9ad8\u304f\u306a\u308a\u3001\u6ede\u7559\u6642\u9593\uff08\u82f1\u8a9e\u7248\uff09(\u53d7\u5bb9\u4f53-\u30ea\u30ac\u30f3\u30c9\u8907\u5408\u4f53\u306e\u5bff\u547d)\u306f\u76f8\u95a2\u3057\u306a\u3044\u3002 \u30ea\u30ac\u30f3\u30c9\u306e\u30ec\u30bb\u30d7\u30bf\u30fc\u3078\u306e\u9ad8\u89aa\u548c\u6027\u7d50\u5408\u306f\u3001\u7d50\u5408\u30a8\u30cd\u30eb\u30ae\u30fc\u306e\u4e00\u90e8\u304c\u30ec\u30bb\u30d7\u30bf\u30fc\u306e\u30b3\u30f3\u30d5\u30a9\u30e1\u30fc\u30b7\u30e7\u30f3\u5909\u5316\u3092\u5f15\u304d\u8d77\u3053\u3059\u305f\u3081\u306b\u4f7f\u7528\u3055\u308c\u3001\u7d50\u679c\u3068\u3057\u3066\u3001\u95a2\u9023\u3059\u308b\u30a4\u30aa\u30f3\u30c1\u30e3\u30cd\u30eb\u307e\u305f\u306f\u9175\u7d20\u306e\u3088\u3046\u306a\u5909\u5316\u3057\u305f\u6319\u52d5\u3092\u3082\u305f\u3089\u3059\u5834\u5408\u306b\u306f\u3001\u751f\u7406\u5b66\u7684\u306b\u91cd\u8981\u3067\u3042\u308b\u3053\u3068\u304c\u591a\u3044\u3002\u751f\u7406\u7684\u53cd\u5fdc\u3092\u8a98\u767a\u3059\u308b\u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3057\u3001\u305d\u306e\u6a5f\u80fd\u3092\u5909\u5316\u3055\u305b\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u53d7\u5bb9\u4f53\u30a2\u30b4\u30cb\u30b9\u30c8\u3068\u547c\u3070\u308c\u308b\u3002 \u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3057\u3066\u3082\u751f\u7406\u53cd\u5fdc\u3092\u6d3b\u6027\u5316\u3067\u304d\u306a\u3044\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u53d7\u5bb9\u4f53\u30a2\u30f3\u30bf\u30b4\u30cb\u30b9\u30c8\u3068\u547c\u3070\u308c\u3066\u3044\u308b\u3002    \u985e\u4f3c\u306e\u7d50\u5408\u89aa\u548c\u6027\u3092\u6301\u30642\u3064\u306e\u30a2\u30b4\u30cb\u30b9\u30c8\u53d7\u5bb9\u4f53\u3078\u306e\u30a2\u30b4\u30cb\u30b9\u30c8\u306e\u7d50\u5408\u306f\u3001\u3069\u308c\u3060\u3051\u306e\u751f\u7406\u7684\u5fdc\u7b54\u3092\u8a98\u767a\u3067\u304d\u308b\u304b(\u3059\u306a\u308f\u3061\u6709\u52b9\u6027)\u3068\u3001\u751f\u7406\u7684\u5fdc\u7b54\u3092\u5f15\u304d\u8d77\u3053\u3059\u306e\u306b\u5fc5\u8981\u306a\u30a2\u30b4\u30cb\u30b9\u30c8\u306e\u6fc3\u5ea6(\u591a\u304f\u306e\u5834\u5408\u3001\u534a\u6700\u5927\u5fdc\u7b54\u3092\u5f15\u304d\u8d77\u3053\u3059\u306e\u306b\u5fc5\u8981\u306a\u6fc3\u5ea6\u3067\u3042\u308bEC50\u3068\u3057\u3066\u6e2c\u5b9a\u3055\u308c\u308b)\u306e\u4e21\u65b9\u306e\u89b3\u70b9\u304b\u3089\u7279\u5fb4\u4ed8\u3051\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u3002 \u9ad8\u89aa\u548c\u6027\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u3068\u306f\u3001\u6bd4\u8f03\u7684\u4f4e\u6fc3\u5ea6\u306e\u30ea\u30ac\u30f3\u30c9\u304c\u30ea\u30ac\u30f3\u30c9\u7d50\u5408\u90e8\u4f4d\u3092\u6700\u5927\u9650\u306b\u5360\u6709\u3057\u3001\u751f\u7406\u53cd\u5fdc\u3092\u8a98\u767a\u3059\u308b\u306e\u306b\u5341\u5206\u306a\u6fc3\u5ea6\u3067\u3042\u308b\u3053\u3068\u3092\u610f\u5473\u3059\u308b\u3002 \u53d7\u5bb9\u4f53\u306e\u89aa\u548c\u6027\u306f\u3001\u963b\u5bb3\u5b9a\u6570\u307e\u305f\u306fKi\u5024(\u53d7\u5bb9\u4f53\u306e50\uff05\u3092\u5360\u3081\u308b\u306e\u306b\u5fc5\u8981\u306a\u6fc3\u5ea6)\u3067\u6e2c\u5b9a\u3055\u308c\u308b\u3002 \u30ea\u30ac\u30f3\u30c9\u89aa\u548c\u6027\u306f\u3001\u7af6\u5408\u7d50\u5408\u5b9f\u9a13\u304b\u3089IC50\u5024\u3068\u3057\u3066\u9593\u63a5\u7684\u306b\u6e2c\u5b9a\u3055\u308c\u308b\u3053\u3068\u304c\u591a\u3044\u304c\u3001\u3053\u3053\u3067\u306f\u3001\u57fa\u6e96\u30ea\u30ac\u30f3\u30c9\u306e\u56fa\u5b9a\u6fc3\u5ea6\u306e50\uff05\u3092\u7f6e\u63db\u3059\u308b\u306e\u306b\u5fc5\u8981\u306a\u30ea\u30ac\u30f3\u30c9\u306e\u6fc3\u5ea6\u304c\u6c7a\u5b9a\u3055\u308c\u308b\u3002 Ki\u5024\u306f\u3001\u30c1\u30a7\u30f3\uff1d\u30d7\u30eb\u30bd\u30d5\u5f0f(Change Prusoff\u5f0f)\u3092\u7528\u3044\u3066IC50\u304b\u3089\u63a8\u5b9a\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u3002 \u30ea\u30ac\u30f3\u30c9\u89aa\u548c\u6027\u306f\u3001\u86cd\u5149\u6d88\u5149\u6cd5\u3001\u7b49\u6e29\u6ef4\u5b9a\u71b1\u91cf\u6e2c\u5b9a\u6cd5\u3001\u8868\u9762\u30d7\u30e9\u30ba\u30e2\u30f3\u5171\u9cf4\u6cd5\u306a\u3069\u306e\u65b9\u6cd5\u3092\u7528\u3044\u3066\u3001\u89e3\u96e2\u5b9a\u6570(Kd)\u3068\u3057\u3066\u76f4\u63a5\u6e2c\u5b9a\u3059\u308b\u3053\u3068\u3082\u3067\u304d\u308b\u3002[4]\u4f4e\u89aa\u548c\u6027\u7d50\u5408(Ki\u30ec\u30d9\u30eb\u304c\u9ad8\u3044)\u3068\u306f\u3001\u7d50\u5408\u90e8\u4f4d\u304c\u6700\u5927\u306b\u5360\u6709\u3055\u308c\u3001\u30ea\u30ac\u30f3\u30c9\u306b\u5bfe\u3059\u308b\u6700\u5927\u306e\u751f\u7406\u5b66\u7684\u53cd\u5fdc\u304c\u9054\u6210\u3055\u308c\u308b\u524d\u306b\u3001\u30ea\u30ac\u30f3\u30c9\u306e\u6bd4\u8f03\u7684\u9ad8\u3044\u6fc3\u5ea6\u304c\u5fc5\u8981\u3067\u3042\u308b\u3053\u3068\u3092\u610f\u5473\u3057\u3066\u3044\u308b\u3002 \u53f3\u306e\u4f8b\u3067\u306f\u30012\u3064\u306e\u7570\u306a\u308b\u30ea\u30ac\u30f3\u30c9\u304c\u540c\u3058\u53d7\u5bb9\u4f53\u7d50\u5408\u90e8\u4f4d\u306b\u7d50\u5408\u3057\u3066\u3044\u308b\u3002 \u793a\u3055\u308c\u3066\u3044\u308b\u30a2\u30b4\u30cb\u30b9\u30c8\u306e\u3046\u3061\u306e1\u3064\u3060\u3051\u304c\u53d7\u5bb9\u4f53\u3092\u6700\u5927\u306b\u523a\u6fc0\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u3001\u3057\u305f\u304c\u3063\u3066\u3001\u5b8c\u5168\u30a2\u30b4\u30cb\u30b9\u30c8(full agonist)\u3068\u5b9a\u7fa9\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u3002 \u751f\u7406\u7684\u5fdc\u7b54\u3092\u90e8\u5206\u7684\u306b\u3057\u304b\u6d3b\u6027\u5316\u3067\u304d\u306a\u3044\u30a2\u30b4\u30cb\u30b9\u30c8\u306f\u3001\u90e8\u5206\u30a2\u30b4\u30cb\u30b9\u30c8(partial agonist)\u3068\u547c\u3070\u308c\u308b\u3002\u3053\u306e\u4f8b\u3067\u306f\u3001\u5b8c\u5168\u30a2\u30b4\u30cb\u30b9\u30c8(\u8d64\u7dda)\u304c\u53d7\u5bb9\u4f53\u3092\u534a\u6700\u5927\u306b\u6d3b\u6027\u5316\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u6fc3\u5ea6\u306f\u3001\u7d045\u00d710-\uff19\u30e2\u30eb(nM\uff1d\u30ca\u30ce\u30e2\u30eb)\u3067\u3042\u308b\u3002  \u53d7\u5bb9\u4f53\u306e\u7d50\u5408\u89aa\u548c\u6027\u304c\u7570\u306a\u308b2\u3064\u306e\u30ea\u30ac\u30f3\u30c9\u3002\u7d50\u5408\u89aa\u548c\u6027\u306f\u3001\u30bf\u30b0\u4ed8\u304d\u30ea\u30ac\u30f3\u30c9\u3068\u3057\u3066\u77e5\u3089\u308c\u308b\u653e\u5c04\u6027\u6a19\u8b58\uff08\u82f1\u8a9e\u7248\uff09\u3055\u308c\u305f\u30ea\u30ac\u30f3\u30c9\u3092\u7528\u3044\u3066\u6700\u3082\u4e00\u822c\u7684\u306b\u6c7a\u5b9a\u3055\u308c\u308b\u3002\u540c\u7a2e\u7af6\u5408\u7d50\u5408\u5b9f\u9a13(Homologous competitive binding experiments)\u3067\u306f\u3001\u30bf\u30b0\u4ed8\u3051\u3055\u308c\u305f\u30ea\u30ac\u30f3\u30c9\u3068\u30bf\u30b0\u4ed8\u3051\u3055\u308c\u3066\u3044\u306a\u3044\u30ea\u30ac\u30f3\u30c9\u3068\u306e\u7d50\u5408\u7af6\u5408\u304c\u884c\u308f\u308c\u308b[5]\u3002 \u8868\u9762\u30d7\u30e9\u30ba\u30e2\u30f3\u5171\u9cf4\u3001\u4e8c\u91cd\u504f\u5149\u5e72\u6e09\u6cd5\u3001\u30de\u30eb\u30c1\u30d1\u30e9\u30e1\u30c8\u30ea\u30c3\u30af\u8868\u9762\u30d7\u30e9\u30ba\u30e2\u30f3\u5171\u9cf4\uff08\u82f1\u8a9e\u7248\uff09(Multi-Parametric Surface Plasmon Resonance; MP-SPR)\u306e\u3088\u3046\u306a\u30e9\u30d9\u30eb\u30d5\u30ea\u30fc\u3067\u3042\u308b\u3053\u3068\u304c\u591a\u3044\u30ea\u30a2\u30eb\u30bf\u30a4\u30e0\u30d9\u30fc\u30b9\u306e\u65b9\u6cd5\u306f\u3001\u6fc3\u5ea6\u30d9\u30fc\u30b9\u306e\u30a2\u30c3\u30bb\u30a4\u304b\u3089\u89aa\u548c\u6027\u3092\u5b9a\u91cf\u5316\u3059\u308b\u3060\u3051\u3067\u306a\u304f\u3001\u7d50\u5408\u3068\u89e3\u96e2\u306e\u901f\u5ea6\u8ad6\u3084\u3001\u5f8c\u306e\u30b1\u30fc\u30b9\u3067\u306f\u7d50\u5408\u6642\u306b\u8a98\u5c0e\u3055\u308c\u308b\u69cb\u9020\u5909\u5316\u304b\u3089\u3082\u5b9a\u91cf\u5316\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u3002 \u307e\u305f\u3001MP-SPR\u306f\u3001\u72ec\u81ea\u306e\u5149\u5b66\u7684\u30bb\u30c3\u30c8\u30a2\u30c3\u30d7\u306b\u3088\u308a\u3001\u9ad8\u5869\u5206\u89e3\u96e2\u7de9\u885d\u6db2\u4e2d\u3067\u306e\u6e2c\u5b9a\u3082\u53ef\u80fd\u3067\u3042\u308b\u3002 \u30de\u30a4\u30af\u30ed\u30b9\u30b1\u30fc\u30eb\u71b1\u6cf3\u52d5\u6cd5\uff08\u82f1\u8a9e\u7248\uff09(Microscale thermophoresis; MST)\u306f\u3001\u56fa\u5b9a\u5316\u3092\u5fc5\u8981\u3068\u3057\u306a\u3044\u65b9\u6cd5\u3067\u3042\u308b[6]\u3002 \u3053\u306e\u65b9\u6cd5\u3067\u306f\u3001\u30ea\u30ac\u30f3\u30c9\u306e\u5206\u5b50\u91cf\u306b\u5236\u9650\u3055\u308c\u308b\u3053\u3068\u306a\u304f\u7d50\u5408\u89aa\u548c\u6027\u3092\u6e2c\u5b9a\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u308b[7]\u3002\u30ea\u30ac\u30f3\u30c9\u3068\u30ec\u30bb\u30d7\u30bf\u30fc\u306e\u7d50\u5408\u89aa\u548c\u6027\u306e\u5b9a\u91cf\u7684\u7814\u7a76\u306b\u304a\u3051\u308b\u7d71\u8a08\u529b\u5b66\u306e\u4f7f\u7528\u306b\u3064\u3044\u3066\u306f\u3001\u69cb\u6210\u5206\u914d\u95a2\u6570\u306b\u95a2\u3059\u308b\u5305\u62ec\u7684\u306a\u8a18\u4e8b\u3092\u53c2\u7167\u306e\u3053\u3068[8]\u3002\u85ac\u52b9\u3068\u7d50\u5408\u89aa\u548c\u6027[\u7de8\u96c6]\u7d50\u5408\u89aa\u548c\u6027\u306e\u30c7\u30fc\u30bf\u3060\u3051\u3067\u306f\u3001\u85ac\u5264\u306e\u5168\u4f53\u7684\u306a\u52b9\u529b\u3092\u6c7a\u5b9a\u3059\u308b\u3053\u3068\u306f\u3067\u304d\u306a\u3044\u3002 \u529b\u4fa1\u306f\u3001\u7d50\u5408\u89aa\u548c\u6027\u3068\u30ea\u30ac\u30f3\u30c9\u6709\u52b9\u6027\u306e\u4e21\u65b9\u304c\u8907\u96d1\u306b\u7d61\u307f\u5408\u3063\u305f\u7d50\u679c\u3067\u3042\u308b\u3002 \u30ea\u30ac\u30f3\u30c9\u52b9\u679c\u3068\u306f\u3001\u6a19\u7684\u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3057\u305f\u969b\u306b\u751f\u7269\u5b66\u7684\u53cd\u5fdc\u3092\u5f15\u304d\u8d77\u3053\u3059\u30ea\u30ac\u30f3\u30c9\u306e\u80fd\u529b\u3068\u3001\u3053\u306e\u53cd\u5fdc\u306e\u5b9a\u91cf\u7684\u306a\u5927\u304d\u3055\u3092\u6307\u3059\u3002 \u3053\u306e\u53cd\u5fdc\u306f\u3001\u751f\u6210\u3055\u308c\u308b\u751f\u7406\u5b66\u7684\u53cd\u5fdc\u306b\u5fdc\u3058\u3066\u3001\u30a2\u30b4\u30cb\u30b9\u30c8\u3001\u30a2\u30f3\u30bf\u30b4\u30cb\u30b9\u30c8\u3001\u307e\u305f\u306f\u9006\u30a2\u30b4\u30cb\u30b9\u30c8(\u53d7\u5bb9\u4f53\u9006\u4f5c\u52d5\u85ac)\u3068\u306a\u308b[9]\u3002\u9078\u629e\u7684\u3068\u975e\u9078\u629e\u7684[\u7de8\u96c6]\u9078\u629e\u7684\u30ea\u30ac\u30f3\u30c9(selective ligands)\u306f\u975e\u5e38\u306b\u9650\u3089\u308c\u305f\u7a2e\u985e\u306e\u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3059\u308b\u50be\u5411\u304c\u3042\u308b\u306e\u306b\u5bfe\u3057\u3001\u975e\u9078\u629e\u7684\u30ea\u30ac\u30f3\u30c9(non-selective ligands)\u306f\u8907\u6570\u306e\u7a2e\u985e\u306e\u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3059\u308b\u3002 \u3053\u306e\u3053\u3068\u306f\u85ac\u7406\u5b66\u306b\u304a\u3044\u3066\u91cd\u8981\u306a\u5f79\u5272\u3092\u679c\u305f\u3057\u3066\u304a\u308a\u3001\u975e\u9078\u629e\u7684\u3067\u3042\u308b\u85ac\u5264\u306f\u3001\u6240\u671b\u306e\u52b9\u679c\u3092\u767a\u751f\u3055\u305b\u308b\u3082\u306e\u306b\u52a0\u3048\u3066\u4ed6\u306e\u8907\u6570\u306e\u53d7\u5bb9\u4f53\u306b\u7d50\u5408\u3059\u308b\u305f\u3081\u3001\u3088\u308a\u591a\u304f\u306e\u60aa\u5f71\u97ff(\u526f\u4f5c\u7528)\uff08\u82f1\u8a9e\u7248\uff09\u3092\u3082\u305f\u3089\u3059\u50be\u5411\u304c\u3042\u308b\u3002\u758e\u6c34\u6027\u30ea\u30ac\u30f3\u30c9[\u7de8\u96c6]\u758e\u6c34\u6027\u30ea\u30ac\u30f3\u30c9(hydrophobic ligands)(\u4f8b\uff1aPIP2)\u3068\u758e\u6c34\u6027\u30bf\u30f3\u30d1\u30af\u8cea(\u4f8b: \u8102\u8cea\u4f9d\u5b58\u6027\u30a4\u30aa\u30f3\u30c1\u30e3\u30cd\u30eb)\u3068\u306e\u8907\u5408\u4f53\u306e\u5834\u5408\u3001\u89aa\u548c\u6027\u306e\u6c7a\u5b9a\u306f\u975e\u7279\u7570\u7684\u306a\u758e\u6c34\u6027\u76f8\u4e92\u4f5c\u7528\u306b\u3088\u3063\u3066\u8907\u96d1\u306b\u306a\u308b\u3002 \u975e\u7279\u7570\u7684\u758e\u6c34\u6027\u76f8\u4e92\u4f5c\u7528\u306f\u3001\u30ea\u30ac\u30f3\u30c9\u306e\u89aa\u548c\u6027\u304c\u9ad8\u3044\u5834\u5408\u306b\u6253\u3061\u52dd\u3064\u3053\u3068\u304c\u3067\u304d\u308b[10]\u3002 \u4f8b\u3048\u3070\u3001PIP2\u306f\u3001PIP2\u4f9d\u5b58\u6027\u30a4\u30aa\u30f3\u30c1\u30e3\u30cd\u30eb\uff08\u82f1\u8a9e\u7248\uff09\u306b\u9ad8\u3044\u89aa\u548c\u6027\u3067\u7d50\u5408\u3059\u308b\u3002\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9[\u7de8\u96c6]\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9(bivalent ligands)\u306f\u3001\u4e0d\u6d3b\u6027\u30ea\u30f3\u30ab\u30fc\u3067\u9023\u7d50\u3055\u308c\u305f2\u3064\u306e\u85ac\u7269\u69d8\u5206\u5b50(\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u307e\u305f\u306f\u30ea\u30ac\u30f3\u30c9)\u3067\u69cb\u6210\u3055\u308c\u3066\u3044\u308b\u3002 \u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9\u306b\u306f\u69d8\u3005\u306a\u7a2e\u985e\u304c\u3042\u308a\u3001\u30d5\u30a1\u30fc\u30de\u30b3\u30d5\u30a9\u30a2\u304c\u4f55\u3092\u6a19\u7684\u3068\u3059\u308b\u304b\u306b\u3088\u3063\u3066\u5206\u985e\u3055\u308c\u308b\u3053\u3068\u304c\u591a\u3044\u3002 \u30db\u30e2\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9(homobivalent ligands)\u306f\u3001\u540c\u3058\u53d7\u5bb9\u4f53\u306e2\u3064\u306e\u30bf\u30a4\u30d7\u3092\u6a19\u7684\u3068\u3057\u3066\u3044\u308b\u3002 \u30d8\u30c6\u30ed\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9(heterobivalent ligands)\u306f\u3001\u7570\u306a\u308b2\u7a2e\u985e\u306e\u53d7\u5bb9\u4f53\u3092\u6a19\u7684\u3068\u3057\u3066\u3044\u308b[11]\u3002 \u30d0\u30a4\u30c8\u30d4\u30c3\u30af\u30fb\u30ea\u30ac\u30f3\u30c9(bitopic ligands)\u306f\u3001\u540c\u3058\u53d7\u5bb9\u4f53\u4e0a\u306e\u30aa\u30eb\u30c8\u30b9\u30c6\u30ea\u30c3\u30af\u7d50\u5408\u90e8\u4f4d\u3068\u30a2\u30ed\u30b9\u30c6\u30ea\u30c3\u30af\u7d50\u5408\u90e8\u4f4d\u3092\u6a19\u7684\u3068\u3057\u3066\u3044\u308b[12]\u3002\u79d1\u5b66\u7814\u7a76\u3067\u306f\u3001\u53d7\u5bb9\u4f53\u4e8c\u91cf\u4f53\uff08\u82f1\u8a9e\u7248\uff09(receptor dimers)\u306e\u7814\u7a76\u3084\u305d\u306e\u6027\u8cea\u3092\u8abf\u3079\u308b\u305f\u3081\u306b\u3001\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9\u304c\u4f7f\u7528\u3055\u308c\u3066\u304d\u305f\u3002 \u3053\u306e\u30af\u30e9\u30b9\u306e\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u30aa\u30d4\u30aa\u30a4\u30c9\u53d7\u5bb9\u4f53\u7cfb\u306e\u7814\u7a76\u4e2d\u306bPhilip S. Portoghese\u3089\u306b\u3088\u3063\u3066\u958b\u62d3\u3055\u308c\u305f[13][14][15]\u3002 \u307e\u305f\u3001\u30b4\u30ca\u30c9\u30c8\u30ed\u30d4\u30f3\u653e\u51fa\u30db\u30eb\u30e2\u30f3\u53d7\u5bb9\u4f53\u306b\u3064\u3044\u3066\u306f\u3001Micheal Conn\u6c0f\u3089\u306b\u3088\u3063\u3066\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9\u304c\u65e9\u304f\u304b\u3089\u5831\u544a\u3055\u308c\u3066\u3044\u308b[16][17]\u3002 \u3053\u308c\u3089\u306e\u521d\u671f\u306e\u5831\u544a\u4ee5\u6765\u3001\u30ab\u30f3\u30ca\u30d3\u30ce\u30a4\u30c9[18]\u3001\u30bb\u30ed\u30c8\u30cb\u30f3[19][20]\u3001\u30aa\u30ad\u30b7\u30c8\u30b7\u30f3[21]\u3001\u30e1\u30e9\u30ce\u30b3\u30eb\u30c1\u30f3\u53d7\u5bb9\u4f53\u7cfb[22][23][24]\u3001\u304a\u3088\u3073GPCR-LIC\u7cfb(\u30c9\u30fc\u30d1\u30df\u30f3D2\u53d7\u5bb9\u4f53\uff08\u82f1\u8a9e\u7248\uff09\u304a\u3088\u3073nACh\u53d7\u5bb9\u4f53\uff08\u82f1\u8a9e\u7248\uff09)\u3092\u542b\u3080\u69d8\u3005\u306aG\u30bf\u30f3\u30d1\u30af\u8cea\u5171\u5f79\u578b\u53d7\u5bb9\u4f53(GPCR)\u7cfb\u306b\u5bfe\u3057\u3066\u591a\u304f\u306e\u4e8c\u4fa1\u30ea\u30ac\u30f3\u30c9\u304c\u5831\u544a\u3055\u308c\u3066\u3044\u308b[11]\u30022\u4fa1\u306e\u30ea\u30ac\u30f3\u30c9\u306f\u901a\u5e38\u30011\u4fa1\u306e\u30ea\u30ac\u30f3\u30c9\u3088\u308a\u3082\u5927\u304d\u304f\u306a\u308b\u50be\u5411\u304c\u3042\u308a\u3001\u3057\u305f\u304c\u3063\u3066\u300c\u85ac\u7269\u69d8\u300d\u3067\u306f\u306a\u3044(\u30ea\u30d4\u30f3\u30b9\u30ad\u30fc\u306e\u30eb\u30fc\u30eb\u30fb\u30aa\u30d6\u30fb\u30d5\u30a1\u30a4\u30d6\u3092\u53c2\u7167)\u3002 \u591a\u304f\u306e\u4eba\u306f\u3001\u3053\u306e\u3053\u3068\u304c\u81e8\u5e8a\u73fe\u5834\u3067\u306e\u9069\u7528\u53ef\u80fd\u6027\u3092\u5236\u9650\u3057\u3066\u3044\u308b\u3068\u8003\u3048\u3066\u3044\u308b[25][26]\u3002 \u3053\u306e\u3088\u3046\u306a\u8003\u3048\u306b\u3082\u304b\u304b\u308f\u3089\u305a\u3001\u524d\u81e8\u5e8a\u52d5\u7269\u8a66\u9a13\u3067\u6210\u529f\u3057\u305f\u3053\u3068\u3092\u5831\u544a\u3057\u3066\u3044\u308b\u30ea\u30ac\u30f3\u30c9\u306f\u6570\u591a\u304f\u5b58\u5728\u3059\u308b[23][24][21][27][28][29]\u3002 \u4e8c\u4fa1\u306e\u30ea\u30ac\u30f3\u30c9\u306e\u4e2d\u306b\u306f\u3001\u4e00\u4fa1\u306e\u30ea\u30ac\u30f3\u30c9\u3068\u6bd4\u8f03\u3057\u3066\u591a\u304f\u306e\u5229\u70b9(\u7d44\u7e54\u9078\u629e\u6027\u3001\u7d50\u5408\u89aa\u548c\u6027\u306e\u5411\u4e0a\u3001\u52b9\u529b\u307e\u305f\u306f\u6709\u52b9\u6027\u306e\u5411\u4e0a\u306a\u3069)\u3092\u6709\u3059\u308b\u3082\u306e\u304c\u3042\u308b\u3053\u3068\u3092\u8003\u3048\u308b\u3068\u3001\u4e8c\u4fa1\u306e\u30ea\u30ac\u30f3\u30c9\u306f\u81e8\u5e8a\u7684\u306b\u3082\u5229\u70b9\u3092\u63d0\u4f9b\u3059\u308b\u53ef\u80fd\u6027\u304c\u3042\u308b\u3002\u30e2\u30ce\u304a\u3088\u3073\u30dd\u30ea\u30c7\u30ba\u30df\u30c3\u30af\u30fb\u30ea\u30ac\u30f3\u30c9[\u7de8\u96c6]\u30bf\u30f3\u30d1\u30af\u8cea\u306e\u30ea\u30ac\u30f3\u30c9\u306f\u3001\u7d50\u5408\u3059\u308b\u30bf\u30f3\u30d1\u30af\u8cea\u9396\u306e\u6570\u306b\u3088\u3063\u3066\u3082\u7279\u5fb4\u3065\u3051\u3089\u308c\u308b\u3002 \u300c\u30e2\u30ce\u30c7\u30ba\u30df\u30c3\u30af\u300d(monodesmic)\u30ea\u30ac\u30f3\u30c9(\u03bc\u03cc\u03bd\u03bf\u03c2: \u5358\u4e00, \u03b4\u03b5\u03c3\u03bc\u03cc\u03c2: \u7d50\u5408)\u306f\u3001\u5358\u4e00\u306e\u30bf\u30f3\u30d1\u30af\u8cea\u9396\u3092\u7d50\u5408\u3059\u308b\u30ea\u30ac\u30f3\u30c9\u3067\u3042\u308a\u3001\u300c\u30dd\u30ea\u30c7\u30ba\u30df\u30c3\u30af\u300d(polydesmic)\u30ea\u30ac\u30f3\u30c9(\u03c0\u03bf\u03bb\u03bf\u03af: \u591a\u6570)[30]\u306f\u30bf\u30f3\u30d1\u30af\u8cea\u8907\u5408\u4f53\u306b\u591a\u304f\u5b58\u5728\u3057\u3001\u8907\u6570\u306e\u30bf\u30f3\u30d1\u30af\u8cea\u9396\u3092\u7d50\u5408\u3059\u308b\u30ea\u30ac\u30f3\u30c9\u3067\u3042\u308a\u3001\u5178\u578b\u7684\u306b\u306f\u30bf\u30f3\u30d1\u30af\u8cea\u306e\u754c\u9762\u307e\u305f\u306f\u305d\u306e\u8fd1\u508d\u306b\u5b58\u5728\u3059\u308b\u3002 \u6700\u8fd1\u306e\u7814\u7a76\u3067\u306f\u3001\u30ea\u30ac\u30f3\u30c9\u306e\u7a2e\u985e\u3084\u7d50\u5408\u90e8\u4f4d\u306e\u69cb\u9020\u304c\u3001\u30bf\u30f3\u30d1\u30af\u8cea\u8907\u5408\u4f53\u306e\u9032\u5316\u3001\u6a5f\u80fd\u3001\u30a2\u30ed\u30b9\u30c6\u30ea\u3001\u30d5\u30a9\u30fc\u30eb\u30c7\u30a3\u30f3\u30b0\u306b\u6df1\u3044\u5f71\u97ff\u3092\u4e0e\u3048\u308b\u3053\u3068\u304c\u660e\u3089\u304b\u306b\u306a\u3063\u3066\u304d\u3066\u3044\u308b[31][32]\u3002\u7279\u6a29\u7684\u8db3\u5834[\u7de8\u96c6]\u7279\u6a29\u7684\u8db3\u5834(privileged scaffold)[33]\u3068\u306f\u3001\u65e2\u77e5\u306e\u533b\u85ac\u54c1\u3084\u751f\u7269\u5b66\u7684\u306b\u6d3b\u6027\u306a\u5316\u5408\u7269\u306e\u7279\u5b9a\u306e\u914d\u5217\u306e\u4e2d\u3067\u7d71\u8a08\u7684\u306b\u518d\u73fe\u6027\u306e\u3042\u308b\u5206\u5b50\u9aa8\u683c\u3084\u5316\u5b66\u7684\u306a\u90e8\u5206\u306e\u3053\u3068\u3067\u3042\u308b\u3002 \u3053\u308c\u3089\u306e\u7279\u6a29\u7684\u306a\u8981\u7d20[34]\u306f\u3001\u65b0\u3057\u3044\u751f\u7269\u5b66\u7684\u6d3b\u6027\u5316\u5408\u7269\u3084\u5316\u5408\u7269\u30e9\u30a4\u30d6\u30e9\u30ea\u3092\u8a2d\u8a08\u3059\u308b\u305f\u3081\u306e\u57fa\u790e\u3068\u3057\u3066\u4f7f\u7528\u3059\u308b\u3053\u3068\u304c\u3067\u304d\u308b\u3002\u7d50\u5408\u6027\u3092\u8abf\u3079\u308b\u305f\u3081\u306b\u7528\u3044\u3089\u308c\u308b\u65b9\u6cd5[\u7de8\u96c6]\u30bf\u30f3\u30d1\u30af\u8cea-\u30ea\u30ac\u30f3\u30c9\u9593\u306e\u76f8\u4e92\u4f5c\u7528\u3092\u7814\u7a76\u3059\u308b\u4e3b\u306a\u65b9\u6cd5\u3068\u3057\u3066\u306f\u3001\u6d41\u4f53\u529b\u5b66\u7684\u624b\u6cd5\u3084\u71b1\u91cf\u8ad6\u7684\u624b\u6cd5\u3001\u5206\u5149\u5b66\u7684\u624b\u6cd5\u3084\u69cb\u9020\u5b66\u7684\u624b\u6cd5\u3001\u305d\u3057\u3066\u30b3\u30f3\u30d4\u30e5\u30fc\u30bf\u306b\u3088\u308b\u5206\u5b50\u30b7\u30df\u30e5\u30ec\u30fc\u30b7\u30e7\u30f3\u624b\u6cd5\u306a\u3069\u304c\u3042\u308b\u3002\u305d\u306e\u4ed6\u306e\u6280\u8853\u3068\u3057\u3066\u306f\u3001\u4ee5\u4e0b\u306e\u3088\u3046\u306a\u3082\u306e\u304c\u3042\u308b\u3002\u86cd\u5149\u5f37\u5ea6(fluorescence intensity)\u4e8c\u5206\u5b50\u86cd\u5149\u88dc\u5b8c(bimolecular fluorescence complementation)FRET(\u86cd\u5149\u5171\u9cf4\u30a8\u30cd\u30eb\u30ae\u30fc\u79fb\u52d5, fluorescent resonance energy transfer)FRET\u6d88\u5149\u8868\u9762\u30d7\u30e9\u30ba\u30e2\u30f3\u5171\u9cf4\u751f\u4f53\u5c64\u5e72\u6e09\u6cd5(bio-layer interferometry)\u5171\u514d\u75ab\u6c88\u964d\u6cd5 \u9593\u63a5ELISA(Coimmunopreciptation indirect ELISA)\u5e73\u8861\u900f\u6790(equilibrium dialysis)\u30b2\u30eb\u96fb\u6c17\u6cf3\u52d5(gel electrophoresis)\u30d5\u30a1\u30fc\u30a6\u30a7\u30b9\u30bf\u30f3\u30d6\u30ed\u30c3\u30c8\u89e3\u6790(far western blot)\u86cd\u5149\u504f\u5149\u7570\u65b9\u6027(fluorescence polarization anisotropy)\u96fb\u5b50\u5e38\u78c1\u6027\u5171\u9cf4(electron paramagnetic resonance)\u30de\u30a4\u30af\u30ed\u30b9\u30b1\u30fc\u30eb\u71b1\u6cf3\u52d5(microscale thermophoresis)\u5206\u5b50\u30b7\u30df\u30e5\u30ec\u30fc\u30b7\u30e7\u30f3\u306b\u3088\u308b\u89e3\u6790\u6cd5\u30b9\u30fc\u30d1\u30fc\u30b3\u30f3\u30d4\u30e5\u30fc\u30bf\u3084\u30d1\u30bd\u30b3\u30f3\u306e\u8a08\u7b97\u80fd\u529b\u304c\u98db\u8e8d\u7684\u306b\u5411\u4e0a\u3057\u305f\u3053\u3068\u3067\u3001\u30bf\u30f3\u30d1\u30af\u8cea\u3068\u30ea\u30ac\u30f3\u30c9\u306e\u76f8\u4e92\u4f5c\u7528\u3092\u8a08\u7b97\u5316\u5b66\u7684\u306b\u7814\u7a76\u3059\u308b\u3053\u3068\u304c\u53ef\u80fd\u306b\u306a\u3063\u305f\u3002 \u4f8b\u3048\u3070\u3001\u304c\u3093\u7814\u7a76\u306e\u305f\u3081\u306b100\u4e07\u53f0\u4ee5\u4e0a\u306e\u4e00\u822c\u7684\u306a\u30d1\u30bd\u30b3\u30f3\u3092\u4e16\u754c\u898f\u6a21\u3067\u30b0\u30ea\u30c3\u30c9\u5316\u3057\u305f\u300cgrid.org\u300d (\u65e5\u672c\u3067\u306f\u300cUD\u304c\u3093\u7814\u7a76\u30d7\u30ed\u30b8\u30a7\u30af\u30c8\u300d\u3068\u3082)\u3068\u3044\u3046\u30d7\u30ed\u30b8\u30a7\u30af\u30c8\u306f2007\u5e744\u6708\u306b\u7d42\u4e86\u3057\u305f\u304c\u3001\u305d\u306e\u5f8c\u3001World Community Grid\u3001Folding@home\u3001Rosetta@home\u306a\u3069\u69d8\u3005\u306a\u30d7\u30ed\u30b8\u30a7\u30af\u30c8\u304c\u9032\u3093\u3067\u3044\u308b\u3002\u95a2\u9023\u9805\u76ee[\u7de8\u96c6]^ \u201cLigand-induced DNA condensation: choosing the model\u201d. Biophysical Journal 89 (4):  2574\u201387. (October 2005). Bibcode:\u00a02005BpJ….89.2574T. doi:10.1529\/biophysj.105.063909. PMC\u00a01366757. PMID\u00a016085765. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1366757\/.\u00a0^ \u201cStatistical-mechanical lattice models for protein-DNA binding in chromatin\u201d. Journal of Physics: Condensed Matter 22 (41):  414105. (October 2010). arXiv:1004.5514. Bibcode:\u00a02010JPCM…22O4105T. doi:10.1088\/0953-8984\/22\/41\/414105. PMID\u00a021386588.\u00a0^ \u201cWater in cavity-ligand recognition\u201d. Journal of the American Chemical Society 132 (34):  12091\u20137. (September 2010). doi:10.1021\/ja1050082. PMC\u00a02933114. PMID\u00a020695475. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2933114\/.\u00a0^ \u201cThe difference between Ki, Kd, IC50, and EC50 values\u201d. The Science Snail (2019\u5e7412\u670831\u65e5). 2020\u5e747\u670819\u65e5\u95b2\u89a7\u3002^ See Homologous competitive binding curves Archived 2007-12-19 at the Wayback Machine., A complete guide to nonlinear regression, curvefit.com.^ \u201cOptical thermophoresis for quantifying the buffer dependence of aptamer binding\u201d. Angewandte Chemie 49 (12):  2238\u201341. (March 2010). doi:10.1002\/anie.200903998. PMID\u00a020186894 (February 24, 2010).\u00a0^ \u201cProtein-binding assays in biological liquids using microscale thermophoresis\u201d. Nature Communications 1 (7):  100. (October 2010). Bibcode:\u00a02010NatCo…1..100W. doi:10.1038\/ncomms1093. PMID\u00a020981028.\u00a0^ Vu-Quoc, L., Configuration integral (statistical mechanics), 2008. this wiki site is down; see this article in the web archive on 2012 April 28. ^ Kenakin, Terrance P. (November 2006). A pharmacology primer: theory, applications, and methods. Academic Press. p.\u00a079. ISBN\u00a0978-0-12-370599-0. https:\/\/books.google.com\/?id=d0phlW5cCmQC&lpg=PA79&dq=potency%20binding%20affinity%20agonist&pg=PA79#v=onepage&q&f=false\u00a0^ Cabanos, C; Wang, M; Han, X; Hansen, SB (8 August 2017). \u201cA Soluble Fluorescent Binding Assay Reveals PIP2 Antagonism of TREK-1 Channels.\u201d. Cell Reports 20 (6):  1287\u20131294. doi:10.1016\/j.celrep.2017.07.034. PMC\u00a05586213. PMID\u00a028793254. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5586213\/.\u00a0^ a b Matera, Carlo; Pucci, Luca; Fiorentini, Chiara; Fucile, Sergio; Missale, Cristina; Grazioso, Giovanni; Clementi, Francesco; Zoli, Michele et al. (2015-08-28). \u201cBifunctional compounds targeting both D2 and non-\u03b17 nACh receptors: Design, synthesis and pharmacological characterization\u201d. European Journal of Medicinal Chemistry 101:  367\u2013383. doi:10.1016\/j.ejmech.2015.06.039. PMID\u00a026164842.\u00a0^ Matera, Carlo; Flammini, Lisa; Quadri, Marta; Vivo, Valentina; Ballabeni, Vigilio; Holzgrabe, Ulrike; Mohr, Klaus; De Amici, Marco et al. (2014-03-21). \u201cBis(ammonio)alkane-type agonists of muscarinic acetylcholine receptors: Synthesis, in vitro functional characterization, and in vivo evaluation of their analgesic activity\u201d. European Journal of Medicinal Chemistry 75:  222\u2013232. doi:10.1016\/j.ejmech.2014.01.032. PMID\u00a024534538.\u00a0^ \u201cNarcotic antagonistic potency of bivalent ligands which contain beta-naltrexamine. Evidence for bridging between proximal recognition sites\u201d. Journal of Medicinal Chemistry 25 (7):  847\u20139. (July 1982). doi:10.1021\/jm00349a016. PMID\u00a07108900.\u00a0^ \u201cOpioid agonist and antagonist bivalent ligands as receptor probes\u201d. Life Sciences 31 (12\u201313):  1283\u20136. (1982). doi:10.1016\/0024-3205(82)90362-9. PMID\u00a06292615.\u00a0^ \u201cHeteromer Induction: An Approach to Unique Pharmacology?\u201d. ACS Chemical Neuroscience 8 (3):  426\u2013428. (January 2017). doi:10.1021\/acschemneuro.7b00002. PMID\u00a028139906.\u00a0^ \u201cGonadotropin-releasing hormone stimulation of luteinizing hormone release: A ligand-receptor-effector model\u201d. Proceedings of the National Academy of Sciences of the United States of America 79 (23):  7307\u201311. (December 1982). Bibcode:\u00a01982PNAS…79.7307B. doi:10.1073\/pnas.79.23.7307. JSTOR\u00a013076. PMC\u00a0347328. PMID\u00a06296828. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC347328\/.\u00a0^ \u201cConversion of a gonadotropin-releasing hormone antagonist to an agonist\u201d. Nature 296 (5858):  653\u20135. (April 1982). Bibcode:\u00a01982Natur.296..653C. doi:10.1038\/296653a0. PMID\u00a06280058.\u00a0^ \u201cSynthesis and biological evaluation of bivalent cannabinoid receptor ligands based on hCB\u2082R selective benzimidazoles reveal unexpected intrinsic properties\u201d. Bioorganic & Medicinal Chemistry 22 (15):  3938\u201346. (August 2014). doi:10.1016\/j.bmc.2014.06.008. PMID\u00a024984935.\u00a0^ \u201cSynthesis of specific bivalent probes that functionally interact with 5-HT(4) receptor dimers\u201d. Journal of Medicinal Chemistry 50 (18):  4482\u201392. (September 2007). doi:10.1021\/jm070552t. PMID\u00a017676726.\u00a0^ \u201cDesign and synthesis of specific probes for human 5-HT4 receptor dimerization studies\u201d. Journal of Medicinal Chemistry 48 (20):  6220\u20138. (October 2005). doi:10.1021\/jm050234z. PMID\u00a016190749.\u00a0^ a b \u201cDesign and Characterization of Superpotent Bivalent Ligands Targeting Oxytocin Receptor Dimers via a Channel-Like Structure\u201d. Journal of Medicinal Chemistry 59 (15):  7152\u201366. (August 2016). doi:10.1021\/acs.jmedchem.6b00564. PMID\u00a027420737.\u00a0^ \u201cA Direct in Vivo Comparison of the Melanocortin Monovalent Agonist Ac-His-DPhe-Arg-Trp-NH2 versus the Bivalent Agonist Ac-His-DPhe-Arg-Trp-PEDG20-His-DPhe-Arg-Trp-NH2: A Bivalent Advantage\u201d. ACS Chemical Neuroscience 8 (6):  1262\u20131278. (February 2017). doi:10.1021\/acschemneuro.6b00399. PMC\u00a05679024. PMID\u00a028128928. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5679024\/.\u00a0^ a b \u201cHeterobivalent ligands target cell-surface receptor combinations in vivo\u201d. Proceedings of the National Academy of Sciences of the United States of America 109 (52):  21295\u2013300. (December 2012). Bibcode:\u00a02012PNAS..10921295X. doi:10.1073\/pnas.1211762109. JSTOR\u00a042553664. PMC\u00a03535626. PMID\u00a023236171. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC3535626\/.\u00a0^ a b \u201cAn in Vitro and in Vivo Investigation of Bivalent Ligands That Display Preferential Binding and Functional Activity for Different Melanocortin Receptor Homodimers\u201d. Journal of Medicinal Chemistry 59 (7):  3112\u201328. (April 2016). doi:10.1021\/acs.jmedchem.5b01894. PMC\u00a05679017. PMID\u00a026959173. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5679017\/.\u00a0^ \u201cDesign strategies for bivalent ligands targeting GPCRs\u201d. ChemMedChem 6 (6):  963\u201374. (June 2011). doi:10.1002\/cmdc.201100101. PMID\u00a021520422.\u00a0^ \u201cBivalent ligands as specific pharmacological tools for G protein-coupled receptor dimers\u201d. Current Drug Discovery Technologies 5 (4):  312\u20138. (December 2008). doi:10.2174\/157016308786733591. PMID\u00a019075611.\u00a0^ \u201cInhibition of Inflammatory and Neuropathic Pain by Targeting a Mu Opioid Receptor\/Chemokine Receptor5 Heteromer (MOR-CCR5)\u201d. Journal of Medicinal Chemistry 58 (21):  8647\u201357. (November 2015). doi:10.1021\/acs.jmedchem.5b01245. PMC\u00a05055304. PMID\u00a026451468. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5055304\/.\u00a0^ \u201cOpioid-induced tolerance and dependence in mice is modulated by the distance between pharmacophores in a bivalent ligand series\u201d. Proceedings of the National Academy of Sciences of the United States of America 102 (52):  19208\u201313. (December 2005). Bibcode:\u00a02005PNAS..10219208D. doi:10.1073\/pnas.0506627102. JSTOR\u00a04152590. PMC\u00a01323165. PMID\u00a016365317. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC1323165\/.\u00a0^ \u201cTargeting putative mu opioid\/metabotropic glutamate receptor-5 heteromers produces potent antinociception in a chronic murine bone cancer model\u201d. European Journal of Pharmacology 743:  48\u201352. (November 2014). doi:10.1016\/j.ejphar.2014.09.008. PMC\u00a04259840. PMID\u00a025239072. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC4259840\/.\u00a0^ \u201cLigand Binding Site Structure Shapes Folding, Assembly and Degradation of Homomeric Protein Complexes.\u201d. Journal of Molecular Biology 431 (19):  3871-3888. (2019). doi:10.1016\/j.jmb.2019.07.014. PMC\u00a06739599. PMID\u00a031306664. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6739599\/.\u00a0^ \u201cLigand Binding Site Structure Influences the Evolution of Protein Complex Function and Topology.\u201d. Cell Reports 22 (12):  3265-3276. (2018). doi:10.1016\/j.celrep.2018.02.085. PMC\u00a05873459. PMID\u00a029562182. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC5873459\/.\u00a0^ \u201cLigand-Binding-Site Structure Shapes Allosteric Signal Transduction and the Evolution of Allostery in Protein Complexes.\u201d. Molecular Biology and Evolution 36 (8):  1711-1727. (2019). doi:10.1093\/molbev\/msz093. PMC\u00a06657754. PMID\u00a031004156. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC6657754\/.\u00a0^ \u201cPrivileged scaffolds for library design and drug discovery\u201d. Current Opinion in Chemical Biology 14 (3):  347\u201361. (June 2010). doi:10.1016\/j.cbpa.2010.02.018. PMC\u00a02908274. PMID\u00a020303320. https:\/\/www.ncbi.nlm.nih.gov\/pmc\/articles\/PMC2908274\/.\u00a0^ \u201cBioCores: identification of a drug\/natural product-based privileged structural motif for small-molecule lead discovery\u201d. Molecular Diversity 14 (1):  193\u2013200. (February 2010). doi:10.1007\/s11030-009-9157-5. 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