Characterization of Drug Binding Sites on α1-Acid Glycoprotein
Characterization of Drug Binding Sites on α1-Acid Glycoprotein
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α1-酸性糖蛋白上药物结合位点的表征
DOI：
10.1248/cpb.38.1688
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发表时间：
1990
影响因子：
1.7
通讯作者：
A. Takadate
中科院分区：
文献类型：
--
作者：
T. Maruyama;M. Otagiri;A. Takadate
用荧光探针置换实验研究了α1-酸性糖蛋白（AGP）上药物结合位点的分类。碱性药物不仅能强烈地取代碱性探针，而且也能取代酸性探针。另一方面，酸性探针被一些对大多数碱性探针没有影响的酸性药物如保泰松和磺胺二甲氧嘧啶所取代。这种矛盾表明碱性药物与酸性药物并不完全共享结合位点。碱性药物结合位点的极性高于酸性药物结合位点。负电荷可能位于前者或其附近，与后者不同。碱性药物结合位点对AGP的构象变化更为敏感。酸性和碱性药物在AGP分子上似乎都有特定的药物结合位点。然而，所有的位移数据并不完全支持两个独立的药物结合位点的可能性。因此，认为这些地点并非完全分离，而是有明显重叠和相互影响是相当合理的。因此，AGP似乎具有一个广泛而灵活的药物结合区域。
The classification of drug binding sites on α1-acid glycoprotein (AGP) was studied by displacement experiments using fluorescent probes. Basic drugs not only displaced basic probes strongly but also acidic probes as well. Acidic probes, on the other hand, were displaced by some acidic drugs such as phenylbutazone and sulfadimethoxine which had no effect on most of the basic probes. This contradiction suggests that the basic drugs do not completely share a binding site with the acidic drugs. The polarity of the basic drug binding site was higher than that of the acidic drug binding site. The negative charges were probably located in or near the former, different from the latter. The basic drug binding site was more sensitive to the conformational change of AGP. It seems that there are particular drug bindign sites on the AGP molecule for acidic and basic drugs. However, all the displacement data do not fully support the possibility of two independent drug binding sites. Therefore, it is rather reasonable to consider that these sites are not completely separated but are significantly overlapped and influenced by each other. Accordingly, AGP seems to have one wide and flexible drug binding area.