Targeting Plasmodium falciparum protein kinases with adenosine analogue-oligoarginine conjugates

Exp Parasitol. 2014 Mar;138:55-62. doi: 10.1016/j.exppara.2014.02.001. Epub 2014 Feb 15.


During the last decade, a vast number of inhibitors, ligands and fluorescent probes have evolved for mammalian protein kinases; however, the suitability of these compounds for studies of evolutionarily divergent eukaryotes has mostly been left beyond the scope of research. Here, we examined whether adenosine analogue-oligoarginine conjugates that had been extensively characterized as efficient inhibitors of the human protein kinases are applicable for targeting Plasmodium protein kinases. We demonstrated that ARCs were not only able to bind to and inhibit a representative member of Plasmodium falciparum kinome (cGMP-dependent protein kinase) in biochemical assay, but also affected the general phosphorylation levels in parasites released from the infected red blood cells upon saponin treatment. These findings urge advantaging of already existing biochemical tools, whose initially generic, but intrinsically "tunable" selectivity profiles could be used for dissection of signaling pathways outside the initially defined group of biological targets.

Keywords: ARC; Fluorescence anisotropy; Malaria; PfPKG; Protein kinase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives*
  • Cells, Cultured
  • Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors*
  • Cyclic GMP-Dependent Protein Kinases / genetics
  • Cyclic GMP-Dependent Protein Kinases / metabolism
  • Erythrocyte Membrane / drug effects
  • Erythrocytes / drug effects
  • Erythrocytes / parasitology
  • Fluorescent Dyes / chemistry
  • Gene Expression Regulation, Enzymologic
  • Humans
  • Image Processing, Computer-Assisted
  • Malaria, Falciparum / drug therapy
  • Microscopy, Confocal
  • Parasitemia / drug therapy
  • Plasmodium falciparum / drug effects*
  • Plasmodium falciparum / enzymology*
  • Protein Kinase Inhibitors / pharmacology*


  • Fluorescent Dyes
  • Protein Kinase Inhibitors
  • Cyclic GMP-Dependent Protein Kinases
  • Adenosine