Pleeter Perri, Lekostaj Jacqueline K, Roepe Paul D
Department of Chemistry, Georgetown University, 37th and O Streets, Washington, DC 20057, USA.
Mol Biochem Parasitol. 2010 Oct;173(2):158-61. doi: 10.1016/j.molbiopara.2010.05.012. Epub 2010 Jun 1.
We utilize the recent successful overexpression of recombinant Plasmodium falciparum multi-drug resistance transporter, purification and reconstitution of the protein, and a novel high affinity chloroquine analogue to probe hypothesized interaction between the transporter and quinoline drugs. Results suggest that PfMDR1 binding sites for chloroquine, mefloquine, and quinine overlap, that P. falciparum chloroquine resistance transporter has intrinsically higher affinity for chloroquine relative to P. falciparum multi-drug resistance transporter, and that there is an isoform specific competition between the two transporters for binding of quinoline antimalarial drugs.
我们利用近期成功实现的重组恶性疟原虫多药耐药转运蛋白的过表达、该蛋白的纯化与重构，以及一种新型高亲和力氯喹类似物，来探究该转运蛋白与喹啉类药物之间假定的相互作用。结果表明，氯喹、甲氟喹和奎宁在PfMDR1上的结合位点重叠，恶性疟原虫氯喹抗性转运蛋白相对于恶性疟原虫多药耐药转运蛋白对氯喹具有更高的内在亲和力，并且这两种转运蛋白在喹啉类抗疟药物结合方面存在亚型特异性竞争。
