UV-triggered affinity capture identifies interactions between the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) and antimalarial agents in live parasitized cells

紫外线触发的亲和力捕获可识别活寄生细胞中恶性疟原虫多药耐药蛋白 1 (PfMDR1) 与抗疟药物之间的相互作用

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作者:Ralf Brunner, Caroline L Ng, Hamed Aissaoui, Myles H Akabas, Christoph Boss, Reto Brun, Paul S Callaghan, Olivier Corminboeuf, David A Fidock, Ithiel J Frame, Bibia Heidmann, Amélie Le Bihan, Paul Jenö, Corinna Mattheis, Suzette Moes, Ingrid B Müller, Michelle Paguio, Paul D Roepe, Romain Siegrist, 

Abstract

A representative of a new class of potent antimalarials with an unknown mode of action was recently described. To identify the molecular target of this class of antimalarials, we employed a photo-reactive affinity capture method to find parasite proteins specifically interacting with the capture compound in living parasitized cells. The capture reagent retained the antimalarial properties of the parent molecule (ACT-213615) and accumulated within parasites. We identified several proteins interacting with the capture compound and established a functional interaction between ACT-213615 and PfMDR1. We surmise that PfMDR1 may play a role in the antimalarial activity of the piperazine-containing compound ACT-213615.

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