潜在抗镰状化药物的生理学和X射线研究。
Physiological and x-ray studies of potential antisickling agents.
作者信息
Abraham D J, Perutz M F, Phillips S E
出版信息
Proc Natl Acad Sci U S A. 1983 Jan;80(2):324-8. doi: 10.1073/pnas.80.2.324.
Abstract
Several aromatic compounds have been found to inhibit the gelling of sickle cell hemoglobin. We have tried to correlate the antigelling activity of such compounds with the stereo-chemistry of their binding sites in the hemoglobin molecule. This approach led to the discovery that two known antilipoproteinemia drugs, clofibrate and gemfibrozil, have antigelling activity. X-ray analysis showed that three pairs of molecules of clofibric acid, the active metabolite of clofibrate, bound to the walls of the internal cavity of deoxyhemoglobin A; only one pair bound to a quite different site, between helices A, E, and H of the alpha chains of carbon monoxide hemoglobin A. Unlike other antigelling agents, clofibric acid and related compounds decrease rather than increase the oxygen affinity of hemoglobin.
摘要
已发现几种芳香族化合物可抑制镰状细胞血红蛋白的胶凝作用。我们试图将这类化合物的抗胶凝活性与其在血红蛋白分子中结合位点的立体化学联系起来。这种方法导致发现两种已知的抗脂蛋白血症药物，氯贝丁酯和吉非贝齐，具有抗胶凝活性。X射线分析表明，氯贝丁酯的活性代谢物氯贝酸的三对分子与脱氧血红蛋白A内腔壁结合；只有一对与一氧化碳血红蛋白A的α链的A、E和H螺旋之间的一个截然不同的位点结合。与其他抗胶凝剂不同，氯贝酸及相关化合物降低而非增加血红蛋白的氧亲和力。
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