title: UV-triggered affinity capture identifies interactions between the Plasmodium falciparum multidrug resistance protein 1 (PfMDR1) and antimalarial agents in live parasitized cells.
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.
authors.affiliation: Medical Parasitology and Infection Biology, Swiss Tropical and Public Health Institute, CH-4002 Basel, Switzerland.
authors.forename: Ralf
authors.initials: R
authors.lastname: Brunner
authors.forename: Caroline L
authors.initials: CL
authors.lastname: Ng
authors.forename: Hamed
authors.initials: H
authors.lastname: Aissaoui
authors.forename: Myles H
authors.initials: MH
authors.lastname: Akabas
authors.forename: Christoph
authors.initials: C
authors.lastname: Boss
authors.forename: Reto
authors.initials: R
authors.lastname: Brun
authors.forename: Paul S
authors.initials: PS
authors.lastname: Callaghan
authors.forename: Olivier
authors.initials: O
authors.lastname: Corminboeuf
authors.forename: David A
authors.initials: DA
authors.lastname: Fidock
authors.forename: Ithiel J
authors.initials: IJ
authors.lastname: Frame
authors.forename: Bibia
authors.initials: B
authors.lastname: Heidmann
authors.forename: Amélie
authors.initials: A
authors.lastname: Le Bihan
authors.forename: Paul
authors.initials: P
authors.lastname: Jenö
authors.forename: Corinna
authors.initials: C
authors.lastname: Mattheis
authors.forename: Suzette
authors.initials: S
authors.lastname: Moes
authors.forename: Ingrid B
authors.initials: IB
authors.lastname: Müller
authors.forename: Michelle
authors.initials: M
authors.lastname: Paguio
authors.forename: Paul D
authors.initials: PD
authors.lastname: Roepe
authors.forename: Romain
authors.initials: R
authors.lastname: Siegrist
authors.forename: Till
authors.initials: T
authors.lastname: Voss
authors.forename: Richard W D
authors.initials: RW
authors.lastname: Welford
authors.forename: Sergio
authors.initials: S
authors.lastname: Wittlin
authors.forename: Christoph
authors.initials: C
authors.lastname: Binkert
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D000962:Antimalarials / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000502:physiology*; D014466:Ultraviolet Rays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000962:Antimalarials
keywords: ACT-213615; Affinity Capture; Drug Action; Mode of Action; Multidrug Transporters; PfMDR1; Photoaffinity Labeling; Plasmodium; Protein Drug Interactions