Palmieri D A, Butterfield D A
Department of Chemistry, University of Kentucky, Lexington 40506-0055.
Biochim Biophys Acta. 1990 May 24;1024(2):285-8. doi: 10.1016/0005-2736(90)90356-s.
The oral administration of 9-amino-1,2,3,4-tetrahydroacridine (THA) is purported to increase the mental function of Alzheimer's disease patients (Summers et al. (1986) N. Engl. J. Med. 315, 1241-1245). Numerous erythrocyte membrane proteins are known to be identical or highly similar to neuronal proteins. In a previous study (Butterfield and Palmieri [1990) Free Radical Res. Commun., in press), we showed that THA greatly increased skeletal protein-protein interactions in erythrocyte membranes as monitored by a spin label specifically bound to membrane proteins. In this report, a structure-activity study has been performed to determine which THA structural components are involved in its effect on the physical state of human erythrocyte membrane skeletal proteins. The results imply that both the planarity of the molecule and the amino group at the 9-position of the parent acridine molecule are important in the mechanism of interaction with membrane proteins.
据称，口服9-氨基-1,2,3,4-四氢吖啶（THA）可改善阿尔茨海默病患者的心理功能（Summers等人，《新英格兰医学杂志》，1986年，第315卷，第1241 - 1245页）。已知许多红细胞膜蛋白与神经元蛋白相同或高度相似。在之前的一项研究中（Butterfield和Palmieri，《自由基研究通讯》，即将发表，1990年），我们发现，通过与膜蛋白特异性结合的自旋标记监测，THA能显著增强红细胞膜中的骨架蛋白 - 蛋白相互作用。在本报告中，我们进行了一项构效关系研究，以确定THA的哪些结构成分参与其对人红细胞膜骨架蛋白物理状态的影响。结果表明，分子的平面性和母体吖啶分子9位上的氨基在与膜蛋白的相互作用机制中都很重要。
