Short communicationPurified Plasmodium falciparum multi-drug resistance protein (PfMDR 1) binds a high affinity chloroquine analogue

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.

This paper shows that PfMDR1 binding sites for chloroquine, mefloquine and quinine overlap, that Plasmodium falciparum chloroquine resistance transporter (PfCRT) has intrinsically higher affinity for CQ relative to PfMDR1, and that PfMDR1 and PfCRT isoforms (allelic forms) compete for quinoline drugs.49